Pub Date : 2021-12-31DOI: 10.1186/s40709-021-00154-5
Junyu Ren, Guoqing Pan, Jun Yang, Ning Xu, Qiong Zhang, Wenliang Li
Background: Gastric cancer (GC) is one of the most common cancers in the digestive system. Circular RNAs (circRNAs) have been found to function as important regulators in the pathogenesis of GC. This study focused on the biological role and molecular mechanism of circ_0000620 in GC progression.
Methods: The expression levels of circ_0000620, microRNA-671-5p (miR-671-5p) and Matrix MetalloProteinase 2 (MMP2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) assay or western blot. The stability of circ_0000620 was confirmed by Ribonuclease R (RNase R) assay. The protein levels were determined by western blot assay. Cell viability, colony formation, cell migratory ability, cell invasive ability and tube formation capacity were respectively examined by CCK-8 assay, colony formation assay, wound healing assay, transwell invasion assay and tube formation assay. The interaction between miR-671-5p and circ_0000620 or MMP2 was validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. The role of circ_0000620 in GC undefined was explored by xenograft tumor assay.
Results: Circ_0000620 was conspicuously upregulated in GC tissues and cells. Circ_0000620 knockdown reduced cell viability, colony formation, migration, invasion and tube formation capacity of GC cells in vitro. Furthermore, MMP2 was upregulated in GC and MMP2 overexpression reversed the anti-tumor response of circ_0000620 knockdown in GC progression. Moreover, circ_0000620 directly interacted with miR-671-5p and circ_0000620 downregulation regulated malignant behaviors of GC cells by upregulating miR-671-5p. In addition, silencing of circ_0000620 inhibited tumor growth in vivo.
Conclusions: Circ_0000620 knockdown inhibited the malignant development of GC partly through modulating the miR-671-5p/MMP2 axis.
{"title":"Circ_0000620 acts as an oncogenic factor in gastric cancer through regulating MMP2 expression via sponging miR-671-5p.","authors":"Junyu Ren, Guoqing Pan, Jun Yang, Ning Xu, Qiong Zhang, Wenliang Li","doi":"10.1186/s40709-021-00154-5","DOIUrl":"https://doi.org/10.1186/s40709-021-00154-5","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most common cancers in the digestive system. Circular RNAs (circRNAs) have been found to function as important regulators in the pathogenesis of GC. This study focused on the biological role and molecular mechanism of circ_0000620 in GC progression.</p><p><strong>Methods: </strong>The expression levels of circ_0000620, microRNA-671-5p (miR-671-5p) and Matrix MetalloProteinase 2 (MMP2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) assay or western blot. The stability of circ_0000620 was confirmed by Ribonuclease R (RNase R) assay. The protein levels were determined by western blot assay. Cell viability, colony formation, cell migratory ability, cell invasive ability and tube formation capacity were respectively examined by CCK-8 assay, colony formation assay, wound healing assay, transwell invasion assay and tube formation assay. The interaction between miR-671-5p and circ_0000620 or MMP2 was validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. The role of circ_0000620 in GC undefined was explored by xenograft tumor assay.</p><p><strong>Results: </strong>Circ_0000620 was conspicuously upregulated in GC tissues and cells. Circ_0000620 knockdown reduced cell viability, colony formation, migration, invasion and tube formation capacity of GC cells in vitro. Furthermore, MMP2 was upregulated in GC and MMP2 overexpression reversed the anti-tumor response of circ_0000620 knockdown in GC progression. Moreover, circ_0000620 directly interacted with miR-671-5p and circ_0000620 downregulation regulated malignant behaviors of GC cells by upregulating miR-671-5p. In addition, silencing of circ_0000620 inhibited tumor growth in vivo.</p><p><strong>Conclusions: </strong>Circ_0000620 knockdown inhibited the malignant development of GC partly through modulating the miR-671-5p/MMP2 axis.</p>","PeriodicalId":50251,"journal":{"name":"Journal of Biological Research-Thessaloniki","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39653099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-23DOI: 10.1186/s40709-021-00153-6
Unbin Chae, Bokyung Kim, HanSeop Kim, Young-Ho Park, Seung Hwan Lee, Sun-Uk Kim, Dong-Seok Lee
Background: Peroxiredoxins (Prxs) are antioxidant enzymes that protect cells from oxidative stress induced by several factors. They regulate several signaling pathways, such as metabolism, immune response, and intracellular reactive oxygen species (ROS) homeostasis. Epithelial-mesenchymal transition (EMT) is a transforming process that induces the loss of epithelial features of cancer cells and the gain of the mesenchymal phenotype. The EMT promotes metastasis and cancer cell progression mediated by several pathways, such as mitogen-activated protein kinases (MAPKs) and epigenetic regulators.
Methods: We used Prx6 overexpressed and downregulated HCT116 cells to study the mechanism between Prx6 and colon cancer. The expression of Prx6, GAPDH, Snail, Twist1, E-cadherin, Vimentin, N-cadherin, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected by Western blotting. Additionally, an animal study for xenograft assay was conducted to explore the function of Prx6 on tumorigenesis. Cell proliferation and migration were determined by IncuCyte Cell Proliferation and colony formation assays.
Results: We confirmed that the expression of Prx6 and EMT signaling highly occurs in HCT116 compared with that in other colon cancer cell lines. Prx6 regulates the EMT signaling pathway by modulating EMT-related transcriptional repressors and mesenchymal genes in HCT116 colon cancer cells. Under the Prx6-overexpressed condition, HCT116 cells proliferation increased significantly. Moreover, the HCT116 cells proliferation decreased in the siPrx6-treated cells. Eleven days after HCT116 cell injection, Prx6 was overexpressed in the HCT116-injected mice, and the tumor volume increased significantly compared with that of the control mice. Furthermore, Prx6 regulates EMT signaling through p38 phosphorylation in colon cancer cells.
Conclusion: We suggested that Prx6 regulates EMT signaling pathway through p38 phosphorylation modulation in HCT116 colon cancer cells.
{"title":"Peroxiredoxin-6 regulates p38-mediated epithelial-mesenchymal transition in HCT116 colon cancer cells.","authors":"Unbin Chae, Bokyung Kim, HanSeop Kim, Young-Ho Park, Seung Hwan Lee, Sun-Uk Kim, Dong-Seok Lee","doi":"10.1186/s40709-021-00153-6","DOIUrl":"https://doi.org/10.1186/s40709-021-00153-6","url":null,"abstract":"<p><strong>Background: </strong>Peroxiredoxins (Prxs) are antioxidant enzymes that protect cells from oxidative stress induced by several factors. They regulate several signaling pathways, such as metabolism, immune response, and intracellular reactive oxygen species (ROS) homeostasis. Epithelial-mesenchymal transition (EMT) is a transforming process that induces the loss of epithelial features of cancer cells and the gain of the mesenchymal phenotype. The EMT promotes metastasis and cancer cell progression mediated by several pathways, such as mitogen-activated protein kinases (MAPKs) and epigenetic regulators.</p><p><strong>Methods: </strong>We used Prx6 overexpressed and downregulated HCT116 cells to study the mechanism between Prx6 and colon cancer. The expression of Prx6, GAPDH, Snail, Twist1, E-cadherin, Vimentin, N-cadherin, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected by Western blotting. Additionally, an animal study for xenograft assay was conducted to explore the function of Prx6 on tumorigenesis. Cell proliferation and migration were determined by IncuCyte Cell Proliferation and colony formation assays.</p><p><strong>Results: </strong>We confirmed that the expression of Prx6 and EMT signaling highly occurs in HCT116 compared with that in other colon cancer cell lines. Prx6 regulates the EMT signaling pathway by modulating EMT-related transcriptional repressors and mesenchymal genes in HCT116 colon cancer cells. Under the Prx6-overexpressed condition, HCT116 cells proliferation increased significantly. Moreover, the HCT116 cells proliferation decreased in the siPrx6-treated cells. Eleven days after HCT116 cell injection, Prx6 was overexpressed in the HCT116-injected mice, and the tumor volume increased significantly compared with that of the control mice. Furthermore, Prx6 regulates EMT signaling through p38 phosphorylation in colon cancer cells.</p><p><strong>Conclusion: </strong>We suggested that Prx6 regulates EMT signaling pathway through p38 phosphorylation modulation in HCT116 colon cancer cells.</p>","PeriodicalId":50251,"journal":{"name":"Journal of Biological Research-Thessaloniki","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39652703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-13DOI: 10.1186/s40709-021-00147-4
Mingchen Li, Kai Li, Yuan Ren
Background: This study aimed to explore the effect of nesfatin-1 on cobalt chloride (CoCl2)-induced hypoxic injury in cardiomyocyte H9c2 cells.
Methods: H9c2 cardiomyocytes were induced by different concentrations of CoCl2 to mimic the hypoxia condition. Cell viability was detected by MTT assay. Cell apoptosis was detected by TUNEL staining and flow cytometry. ROS production was detected using the fluorescence probe DCFH-DA. The mitochondrial membrane potential (MMP) was detected using the TMRE method. The levels of released lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were detected using the commercial kits. The protein levels of MAPK signaling members (p-JNK1/2, p-ERK1/2, and p-p38) and Notch1 signaling members (Notch1, Hes 1, and Jagged 1) were detected by Western blot.
Results: CoCl2 significantly promoted cell apoptosis, increased LDH leakage, MDA concentration, and decreased cell viability, SOD activity, GSH production, and CAT activity. CoCl2-induced hypoxic injury in H9c2 cells was partially restored by nesfatin-1 treatment. Moreover, nesfatin-1 treatment attenuated CoCl2-induced increase in ROS production and mitochondrial dysfunction, decreased mitochondrial membrane potential, Bax/Bcl-2 imbalance, as well as c-caspase-9 and c-caspase-3 levels. Moreover, nesfatin-1 treatment inhibited the activation of MAPK and Notch1 signaling pathways.
Conclusions: Nesfatin-1 could effectively protect H9c2 cells against CoCl2-induced hypoxic injury by blocking MAPK and Notch1 signaling pathways, suggesting that nesfatin-1 might be a promising therapeutic agent for hypoxic cardiac injury.
{"title":"Nesfatin-1 protects H9c2 cardiomyocytes against cobalt chloride-induced hypoxic injury by modulating the MAPK and Notch1 signaling pathways.","authors":"Mingchen Li, Kai Li, Yuan Ren","doi":"10.1186/s40709-021-00147-4","DOIUrl":"https://doi.org/10.1186/s40709-021-00147-4","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to explore the effect of nesfatin-1 on cobalt chloride (CoCl<sub>2</sub>)-induced hypoxic injury in cardiomyocyte H9c2 cells.</p><p><strong>Methods: </strong>H9c2 cardiomyocytes were induced by different concentrations of CoCl<sub>2</sub> to mimic the hypoxia condition. Cell viability was detected by MTT assay. Cell apoptosis was detected by TUNEL staining and flow cytometry. ROS production was detected using the fluorescence probe DCFH-DA. The mitochondrial membrane potential (MMP) was detected using the TMRE method. The levels of released lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were detected using the commercial kits. The protein levels of MAPK signaling members (p-JNK1/2, p-ERK1/2, and p-p38) and Notch1 signaling members (Notch1, Hes 1, and Jagged 1) were detected by Western blot.</p><p><strong>Results: </strong>CoCl<sub>2</sub> significantly promoted cell apoptosis, increased LDH leakage, MDA concentration, and decreased cell viability, SOD activity, GSH production, and CAT activity. CoCl<sub>2</sub>-induced hypoxic injury in H9c2 cells was partially restored by nesfatin-1 treatment. Moreover, nesfatin-1 treatment attenuated CoCl<sub>2</sub>-induced increase in ROS production and mitochondrial dysfunction, decreased mitochondrial membrane potential, Bax/Bcl-2 imbalance, as well as c-caspase-9 and c-caspase-3 levels. Moreover, nesfatin-1 treatment inhibited the activation of MAPK and Notch1 signaling pathways.</p><p><strong>Conclusions: </strong>Nesfatin-1 could effectively protect H9c2 cells against CoCl<sub>2</sub>-induced hypoxic injury by blocking MAPK and Notch1 signaling pathways, suggesting that nesfatin-1 might be a promising therapeutic agent for hypoxic cardiac injury.</p>","PeriodicalId":50251,"journal":{"name":"Journal of Biological Research-Thessaloniki","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39413056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Cervical cancer (CC) is one of the most common and malignant tumors in women. In this study, we aim to explore the role and mechanism of F-box and leucine rich repeat protein 19 antisense RNA 1 (FBXL19-AS1), a novel long-chain non coding RNA (lncRNA) with marked roles in a variety of tumors, in regulating the proliferation and metastasis of CC.
Methods: The expression of FBXL19-AS1, miR-193a-5p and COL1A1 were detected by RT-PCR and western blot. Gain- and loss-of functional assays of FBXL19-AS1 and miR-193a-5p were performed in CC cell lines in vitro or in vivo. The proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT) of CC cells were determined.
Results: FBXL19-AS1 and COL1A1 were significantly up-regulated in CC tissues, while miR-193a-5p was significantly down-regulated. Overexpression of FBXL19-AS1 significantly promoted the proliferation, migration, invasion, EMT and growth of CC cells and inhibited apoptosis, while knockdown of FBXL19-AS1 had the opposite effects. On the other hand, miR-193a-5p inhibited the proliferation and metastasis of CC cells. Mechanistically, FBXL19-AS1 functioned as a competitive endogenous RNA (ceRNA) and inhibited the expression of miR-193a-5p, which targeted at the 3'-UTR site of COL1A1 and negatively regulated COL1A1 expression.
Conclusions: FBXL19-AS1 promotes the proliferation and metastasis of CC cells by sponging miR-193a-5p and up-regulating COL1A1.
{"title":"LncRNA FBXL19-AS1 promotes proliferation and metastasis of cervical cancer through upregulating COL1A1 as a sponge of miR-193a-5p.","authors":"Xiaoyong Huang, Haiyan Shi, Xinghai Shi, Xuemei Jiang","doi":"10.1186/s40709-021-00151-8","DOIUrl":"https://doi.org/10.1186/s40709-021-00151-8","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) is one of the most common and malignant tumors in women. In this study, we aim to explore the role and mechanism of F-box and leucine rich repeat protein 19 antisense RNA 1 (FBXL19-AS1), a novel long-chain non coding RNA (lncRNA) with marked roles in a variety of tumors, in regulating the proliferation and metastasis of CC.</p><p><strong>Methods: </strong>The expression of FBXL19-AS1, miR-193a-5p and COL1A1 were detected by RT-PCR and western blot. Gain- and loss-of functional assays of FBXL19-AS1 and miR-193a-5p were performed in CC cell lines in vitro or in vivo. The proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT) of CC cells were determined.</p><p><strong>Results: </strong>FBXL19-AS1 and COL1A1 were significantly up-regulated in CC tissues, while miR-193a-5p was significantly down-regulated. Overexpression of FBXL19-AS1 significantly promoted the proliferation, migration, invasion, EMT and growth of CC cells and inhibited apoptosis, while knockdown of FBXL19-AS1 had the opposite effects. On the other hand, miR-193a-5p inhibited the proliferation and metastasis of CC cells. Mechanistically, FBXL19-AS1 functioned as a competitive endogenous RNA (ceRNA) and inhibited the expression of miR-193a-5p, which targeted at the 3'-UTR site of COL1A1 and negatively regulated COL1A1 expression.</p><p><strong>Conclusions: </strong>FBXL19-AS1 promotes the proliferation and metastasis of CC cells by sponging miR-193a-5p and up-regulating COL1A1.</p>","PeriodicalId":50251,"journal":{"name":"Journal of Biological Research-Thessaloniki","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39317071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Circular RNAs (circRNAs) have been reported to play an important role in tumor progression in various cancer types, including gastric cancer. The aim of this study was to investigate the role of circCNIH4 (hsa_circ_0000190) in gastric cancer and the underlying mechanism.
Methods: The expression levels of circCNIH4 and Wnt antagonist genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of β-catenin, Ki67, Dickkopf 2 (DKK2) and Frizzled related protein (FRZB) were measured by western blot. Ectopic overexpression or knockdown of circCNIH4, proliferation, apoptosis, migration and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assay in vitro, and in vivo experiment, were employed to assess the role of circCNIH4 in gastric cancer.
Results: CircCNIH4 was downregulated in gastric cancer tissues and cells. Overexpression of circCNIH4 inhibited gastric cancer cell proliferation, migration and invasion and promoted apoptosis by inactivating Wnt/β-catenin pathway in vitro. CircCNIH4 induced the expression of DKK2 and FRZB in gastric cancer cells. Moreover, silencing of DKK2 or FRZB reversed circCNIH4 overexpression-mediated effects on gastric cancer cells. Additionally, circCNIH4 suppressed tumor growth via regulating DKK2 and FRZB expression in gastric cancer in vivo.
Conclusion: Our study demonstrated that circCNIH4 played a tumor-inhibiting role through upregulating DKK2 and FRZB expression and suppressing Wnt/β-catenin pathway in gastric cancer, which might provide a potential biomarker for the diagnosis and treatment of gastric cancer.
背景:环状rna (circRNAs)已被报道在包括胃癌在内的各种癌症类型的肿瘤进展中发挥重要作用。本研究的目的是探讨circCNIH4 (hsa_circ_0000190)在胃癌中的作用及其潜在机制。方法:采用实时荧光定量聚合酶链式反应(qRT-PCR)检测circCNIH4和Wnt拮抗剂基因的表达水平。western blot检测β-catenin、Ki67、dickkopf2 (DKK2)和frzledrelated protein (FRZB)蛋白水平。采用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2- h -溴化四氮唑(MTT)、体外流式细胞术、transwell实验和体内实验,探讨了circCNIH4异位过表达或下调、增殖、凋亡、迁移和侵袭作用。结果:CircCNIH4在胃癌组织和细胞中表达下调。体外实验表明,过表达circCNIH4通过灭活Wnt/β-catenin通路,抑制胃癌细胞增殖、迁移和侵袭,促进凋亡。CircCNIH4诱导胃癌细胞中DKK2和FRZB的表达。此外,DKK2或FRZB的沉默逆转了circCNIH4过表达介导的胃癌细胞效应。此外,circCNIH4在体内通过调节DKK2和FRZB在胃癌中的表达抑制肿瘤生长。结论:我们的研究表明,circCNIH4通过上调DKK2和FRZB的表达,抑制Wnt/β-catenin通路在胃癌中发挥肿瘤抑制作用,可能为胃癌的诊断和治疗提供潜在的生物标志物。
{"title":"CircCNIH4 inhibits gastric cancer progression via regulating DKK2 and FRZB expression and Wnt/β-catenin pathway.","authors":"Qi Shi, Chuanwen Zhou, Rui Xie, Miaomiao Li, Peng Shen, Yining Lu, Shijie Ma","doi":"10.1186/s40709-021-00140-x","DOIUrl":"https://doi.org/10.1186/s40709-021-00140-x","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) have been reported to play an important role in tumor progression in various cancer types, including gastric cancer. The aim of this study was to investigate the role of circCNIH4 (hsa_circ_0000190) in gastric cancer and the underlying mechanism.</p><p><strong>Methods: </strong>The expression levels of circCNIH4 and Wnt antagonist genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of β-catenin, Ki67, Dickkopf 2 (DKK2) and Frizzled related protein (FRZB) were measured by western blot. Ectopic overexpression or knockdown of circCNIH4, proliferation, apoptosis, migration and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assay in vitro, and in vivo experiment, were employed to assess the role of circCNIH4 in gastric cancer.</p><p><strong>Results: </strong>CircCNIH4 was downregulated in gastric cancer tissues and cells. Overexpression of circCNIH4 inhibited gastric cancer cell proliferation, migration and invasion and promoted apoptosis by inactivating Wnt/β-catenin pathway in vitro. CircCNIH4 induced the expression of DKK2 and FRZB in gastric cancer cells. Moreover, silencing of DKK2 or FRZB reversed circCNIH4 overexpression-mediated effects on gastric cancer cells. Additionally, circCNIH4 suppressed tumor growth via regulating DKK2 and FRZB expression in gastric cancer in vivo.</p><p><strong>Conclusion: </strong>Our study demonstrated that circCNIH4 played a tumor-inhibiting role through upregulating DKK2 and FRZB expression and suppressing Wnt/β-catenin pathway in gastric cancer, which might provide a potential biomarker for the diagnosis and treatment of gastric cancer.</p>","PeriodicalId":50251,"journal":{"name":"Journal of Biological Research-Thessaloniki","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39288891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-08-04DOI: 10.1186/s40709-021-00149-2
Umesh C Halder
Background: Novel Coronavirus disease 2019 or COVID-19 has become a threat to human society due to fast spreading and increasing mortality. It uses vertebrate hosts and presently deploys humans. Life cycle and pathogenicity of SARS-CoV-2 have already been deciphered and possible drug target trials are on the way.
Results: The present study was aimed to analyze Non-Structural Proteins that include conserved enzymes of SARS-CoV-2 like papain-like protease, main protease, Replicase, RNA-dependent RNA polymerase, methyltransferase, helicase, exoribonuclease and endoribonucleaseas targets to all known drugs. A bioinformatic based web server Drug ReposeER predicted several drug binding motifs in these analyzed proteins. Results revealed that anti-viral drugs Darunavir,Amprenavir, Rimantadine and Saquinavir were the most potent to have 3D-drug binding motifs that were closely associated with the active sites of the SARS-CoV-2 enzymes .
Conclusions: Repurposing of the antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir to treat COVID-19 patients could be useful that can potentially prevent human mortality.
{"title":"Predicted antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir can potentially bind to neutralize SARS-CoV-2 conserved proteins.","authors":"Umesh C Halder","doi":"10.1186/s40709-021-00149-2","DOIUrl":"https://doi.org/10.1186/s40709-021-00149-2","url":null,"abstract":"<p><strong>Background: </strong>Novel Coronavirus disease 2019 or COVID-19 has become a threat to human society due to fast spreading and increasing mortality. It uses vertebrate hosts and presently deploys humans. Life cycle and pathogenicity of SARS-CoV-2 have already been deciphered and possible drug target trials are on the way.</p><p><strong>Results: </strong>The present study was aimed to analyze Non-Structural Proteins that include conserved enzymes of SARS-CoV-2 like papain-like protease, main protease, Replicase, RNA-dependent RNA polymerase, methyltransferase, helicase, exoribonuclease and endoribonucleaseas targets to all known drugs. A bioinformatic based web server Drug ReposeER predicted several drug binding motifs in these analyzed proteins. Results revealed that anti-viral drugs Darunavir,Amprenavir, Rimantadine and Saquinavir were the most potent to have 3D-drug binding motifs that were closely associated with the active sites of the SARS-CoV-2 enzymes .</p><p><strong>Conclusions: </strong> Repurposing of the antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir to treat COVID-19 patients could be useful that can potentially prevent human mortality.</p>","PeriodicalId":50251,"journal":{"name":"Journal of Biological Research-Thessaloniki","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39274050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Although the cellulose microfibril organization in guard cell (GC) walls play a crucial role in the mechanism of the stomatal function, recent work showed that matrix cell wall materials are also involved. Especially in the kidney-shaped stomata of the fern Asplenium nidus, callose actively participates in the mechanism of opening and closure of the stomatal pore.
Scope: The present review briefly presents and discusses recent findings concerning the distribution and role of callose in the kidney-shaped stomata of the dicotyledon Vigna sinensis as well as in the dumbbell-shaped stomata of the monocotyledon Zea mays.
Conclusion: The discussed data support that, in both categories of angiosperm stomata, callose is implicated in the mechanism of stomatal pore formation and stomata function by locally affecting the mechanical properties of the GC cell walls.
{"title":"Callose: a multifunctional (1, 3)-β-D-glucan involved in morphogenesis and function of angiosperm stomata.","authors":"Panagiotis Apostolakos, Eleni Giannoutsou, Basil Galatis","doi":"10.1186/s40709-021-00150-9","DOIUrl":"https://doi.org/10.1186/s40709-021-00150-9","url":null,"abstract":"<p><strong>Background: </strong>Although the cellulose microfibril organization in guard cell (GC) walls play a crucial role in the mechanism of the stomatal function, recent work showed that matrix cell wall materials are also involved. Especially in the kidney-shaped stomata of the fern Asplenium nidus, callose actively participates in the mechanism of opening and closure of the stomatal pore.</p><p><strong>Scope: </strong>The present review briefly presents and discusses recent findings concerning the distribution and role of callose in the kidney-shaped stomata of the dicotyledon Vigna sinensis as well as in the dumbbell-shaped stomata of the monocotyledon Zea mays.</p><p><strong>Conclusion: </strong>The discussed data support that, in both categories of angiosperm stomata, callose is implicated in the mechanism of stomatal pore formation and stomata function by locally affecting the mechanical properties of the GC cell walls.</p>","PeriodicalId":50251,"journal":{"name":"Journal of Biological Research-Thessaloniki","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39274056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-20DOI: 10.1186/s40709-021-00148-3
Androulla N Miliotou, Dionysia Papagiannopoulou, Efthymia Vlachaki, Martina Samiotaki, Dimitra Laspa, Stamatia Theodoridou, Asterios S Tsiftsoglou, Lefkothea C Papadopoulou
Background: α-Thalassemia, a congenital hemoglobinopathy, is characterized by deficiency and/or reduced levels of α-globin chains in serious forms of α-thalassemia (HbH disease/Hb Bart's). This research work deals with a Protein Replacement Therapy approach in order to manage α-thalassemia manifestations, caused by the excess of β-globin chain into HbH RBCs. The main goal was to produce the recombinant human α-globin chain in fusion with TAT, a Protein Transduction Domain, to ex vivo deliver it into HbH patients RBCs, to replace the endogenous missing α-globin chain.
Results: Cloning of the α-globin coding sequence, fused to the nucleotide sequence of TAT peptide was conducted and the human recombinant fusion proteins, 10xHis-XaSITE-α-globin-HA and 10xHis-XaSITE-TAT-α-globin-HA were produced. The ability of human recombinant 10xHis-XaSITE-α-globin-HA to interact in vitro with the previously produced 10xHis-XaSITE-TAT-β-globin-HA and form α-/β-globin heterodimers, was assessed and confirmed by size exclusion chromatography. The recombinant 10xHis-XaSITE-TAT-α-globin-HA was successfully delivered into human proerythroid K-562 cells, during the preliminary transduction evaluation experiments. Finally, the recombinant, TAT-fused α-globin was successfully transduced into RBCs, derived from HbH patients and reduced the formation of HbH-Inclusion Bodies, known to contain harmful β4-globin chain tetramers.
Conclusions: Our data confirm the successful ex vivo transduction of recombinant α-globin chains in HbH RBCs to replace the missing a-globin chain and reduce the HbH-inclusion bodies, seen in α-thalassemias. These findings broaden the possibility of applying a Protein Replacement Therapy approach to module sever forms of α-thalassemia, using recombinant α-globin chains, through PTD technology.
背景:α-地中海贫血是一种先天性血红蛋白病,在严重的α-地中海贫血(HbH病/Hb Bart's)中以α-珠蛋白链缺乏和/或水平降低为特征。这项研究工作涉及蛋白质替代疗法的方法,以管理α-地中海贫血的表现,过量的β-珠蛋白链进入HbH红细胞。主要目的是制备与TAT(一种蛋白质转导结构域)融合的重组人α-珠蛋白链,并将其体外输送到HbH患者的红细胞中,以取代内源性缺失的α-珠蛋白链。结果:克隆α-珠蛋白编码序列,与TAT肽核苷酸序列融合,获得重组融合蛋白10xHis-XaSITE-α-globin-HA和10xHis-XaSITE-TAT-α-globin-HA。人重组10xHis-XaSITE-α-球蛋白- ha与先前制备的10xHis-XaSITE- tat -β-球蛋白- ha在体外相互作用并形成α-/β-球蛋白异源二聚体的能力,通过尺寸排斥层析进行评估和确认。在初步转导评估实验中,重组蛋白10xHis-XaSITE-TAT-α-球蛋白- ha成功转染人原红细胞K-562细胞。最后,重组的、融合了tat的α-珠蛋白被成功地转导到来自HbH患者的红细胞中,并减少了已知含有有害的β4-珠蛋白链四聚体的HbH包涵体的形成。结论:我们的数据证实了重组α-珠蛋白链在HbH红细胞中的成功体外转导,以取代缺失的a-珠蛋白链并减少HbH包涵体,这在α-地中海贫血中可见。这些发现拓宽了通过PTD技术,利用重组α-珠蛋白链,将蛋白质替代疗法应用于不同形式α-地中海贫血的可能性。
{"title":"PTD-mediated delivery of α-globin chain into Κ-562 erythroleukemia cells and α-thalassemic (HBH) patients' RBCs ex vivo in the frame of Protein Replacement Therapy.","authors":"Androulla N Miliotou, Dionysia Papagiannopoulou, Efthymia Vlachaki, Martina Samiotaki, Dimitra Laspa, Stamatia Theodoridou, Asterios S Tsiftsoglou, Lefkothea C Papadopoulou","doi":"10.1186/s40709-021-00148-3","DOIUrl":"https://doi.org/10.1186/s40709-021-00148-3","url":null,"abstract":"<p><strong>Background: </strong>α-Thalassemia, a congenital hemoglobinopathy, is characterized by deficiency and/or reduced levels of α-globin chains in serious forms of α-thalassemia (HbH disease/Hb Bart's). This research work deals with a Protein Replacement Therapy approach in order to manage α-thalassemia manifestations, caused by the excess of β-globin chain into HbH RBCs. The main goal was to produce the recombinant human α-globin chain in fusion with TAT, a Protein Transduction Domain, to ex vivo deliver it into HbH patients RBCs, to replace the endogenous missing α-globin chain.</p><p><strong>Results: </strong>Cloning of the α-globin coding sequence, fused to the nucleotide sequence of TAT peptide was conducted and the human recombinant fusion proteins, 10xHis-Xa<sub>SITE</sub>-α-globin-HA and 10xHis-Xa<sub>SITE</sub>-TAT-α-globin-HA were produced. The ability of human recombinant 10xHis-Xa<sub>SITE</sub>-α-globin-HA to interact in vitro with the previously produced 10xHis-Xa<sub>SITE</sub>-TAT-β-globin-HA and form α-/β-globin heterodimers, was assessed and confirmed by size exclusion chromatography. The recombinant 10xHis-Xa<sub>SITE</sub>-TAT-α-globin-HA was successfully delivered into human proerythroid K-562 cells, during the preliminary transduction evaluation experiments. Finally, the recombinant, TAT-fused α-globin was successfully transduced into RBCs, derived from HbH patients and reduced the formation of HbH-Inclusion Bodies, known to contain harmful β<sub>4</sub>-globin chain tetramers.</p><p><strong>Conclusions: </strong>Our data confirm the successful ex vivo transduction of recombinant α-globin chains in HbH RBCs to replace the missing a-globin chain and reduce the HbH-inclusion bodies, seen in α-thalassemias. These findings broaden the possibility of applying a Protein Replacement Therapy approach to module sever forms of α-thalassemia, using recombinant α-globin chains, through PTD technology.</p>","PeriodicalId":50251,"journal":{"name":"Journal of Biological Research-Thessaloniki","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40709-021-00148-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39202459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-16DOI: 10.1186/s40709-021-00146-5
Jia-Jie Liang, Hu Peng, Jiao-Jiao Wang, Xiao-Hui Liu, Lan Ma, Yi-Ran Ni, Huai-Jie Yang, Yan-Qiong Zhang, Wen-Bing Ai, Jiang-Feng Wu
E proteins are transcriptional regulators that regulate many developmental processes in animals and lymphocytosis and leukemia in Homo sapiens. In particular, E2A, a member of the E protein family, plays a major role in the transcriptional regulatory network that promotes the differentiation and development of B and T lymphocytes. E2A-mediated transcriptional regulation usually requires the formation of E2A dimers, which then bind to coregulators. In this review, we summarize the mechanisms by which E2A participates in transcriptional regulation from a structural perspective. More specifically, the C-terminal helix-loop-helix (HLH) region of the basic HLH (bHLH) domain first dimerizes, and then the activation domains of E2A bind to different coactivators or corepressors in different cell contexts, resulting in histone acetylation or deacetylation, respectively. Then, the N-terminal basic region (b) of the bHLH domain binds to or dissociates from a specific DNA motif (E-box sequence). Last, trans-activation or trans-repression occurs. We also summarize the properties of these E2A domains and their interactions with the domains of other proteins. The feasibility of developing drugs based on these domains is discussed.
{"title":"Relationship between the structure and function of the transcriptional regulator E2A.","authors":"Jia-Jie Liang, Hu Peng, Jiao-Jiao Wang, Xiao-Hui Liu, Lan Ma, Yi-Ran Ni, Huai-Jie Yang, Yan-Qiong Zhang, Wen-Bing Ai, Jiang-Feng Wu","doi":"10.1186/s40709-021-00146-5","DOIUrl":"https://doi.org/10.1186/s40709-021-00146-5","url":null,"abstract":"<p><p>E proteins are transcriptional regulators that regulate many developmental processes in animals and lymphocytosis and leukemia in Homo sapiens. In particular, E2A, a member of the E protein family, plays a major role in the transcriptional regulatory network that promotes the differentiation and development of B and T lymphocytes. E2A-mediated transcriptional regulation usually requires the formation of E2A dimers, which then bind to coregulators. In this review, we summarize the mechanisms by which E2A participates in transcriptional regulation from a structural perspective. More specifically, the C-terminal helix-loop-helix (HLH) region of the basic HLH (bHLH) domain first dimerizes, and then the activation domains of E2A bind to different coactivators or corepressors in different cell contexts, resulting in histone acetylation or deacetylation, respectively. Then, the N-terminal basic region (b) of the bHLH domain binds to or dissociates from a specific DNA motif (E-box sequence). Last, trans-activation or trans-repression occurs. We also summarize the properties of these E2A domains and their interactions with the domains of other proteins. The feasibility of developing drugs based on these domains is discussed.</p>","PeriodicalId":50251,"journal":{"name":"Journal of Biological Research-Thessaloniki","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40709-021-00146-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39192431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-28DOI: 10.1186/s40709-021-00145-6
Jingpeng Wang, Shuyuan Li, Gaofeng Zhang, Huihua Han
Background: Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression.
Methods: The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay.
Results: Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo.
Conclusion: Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.
背景:七氟醚(Sev)是一种常用的挥发性麻醉剂,据报道可抑制结直肠癌(CRC)的发生。环状rna (circRNAs)被发现参与CRC的发病机制。本研究旨在揭示hsa_circ_0000231在sev介导的CRC进展中的机制。方法:采用实时荧光定量聚合酶链式反应(qRT-PCR)检测hsa_circ_0000231和microRNA-622 (miR-622)的表达。western blot检测蛋白水平。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)、细胞集落形成和DNA含量测定法观察细胞增殖情况。采用Annexin v -异硫氰酸荧光素和碘化丙啶双染色法和caspase 3活性测定法检测细胞凋亡。细胞迁移和侵袭分别通过创面愈合和跨井侵袭试验进行研究。hsa_circ_0000231和miR-622之间的推定关系通过环状RNA Interactome在线数据库预测,并通过双荧光素酶报告基因和RNA免疫沉淀试验进行鉴定。通过体内实验研究hsa_circ_0000231对sev介导的肿瘤形成的影响。结果:与对照组相比,Hsa_circ_0000231在结直肠癌组织和细胞中表达上调,miR-622表达下调。Sev处理降低了hsa_circ_0000231的表达,但增加了CRC细胞中miR-622的表达。Sev处理抑制细胞增殖、迁移和侵袭,诱导细胞凋亡。Hsa_circ_0000231过表达恢复了sev介导的CRC体外进展。此外,hsa_circ_0000231作为miR-622的海绵,miR-622抑制剂逆转了hsa_circ_0000231沉默对CRC过程的影响。此外,Sev治疗通过调节体内hsa_circ_0000231抑制肿瘤生长。结论:Hsa_circ_0000231通过海绵化miR-622减弱了sev引起的抑制对结直肠癌发展的影响。这一发现可能为接受手术的结直肠癌患者提供合适的麻醉方案。
{"title":"Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622.","authors":"Jingpeng Wang, Shuyuan Li, Gaofeng Zhang, Huihua Han","doi":"10.1186/s40709-021-00145-6","DOIUrl":"https://doi.org/10.1186/s40709-021-00145-6","url":null,"abstract":"<p><strong>Background: </strong>Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression.</p><p><strong>Methods: </strong>The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay.</p><p><strong>Results: </strong>Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo.</p><p><strong>Conclusion: </strong>Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.</p>","PeriodicalId":50251,"journal":{"name":"Journal of Biological Research-Thessaloniki","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2021-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40709-021-00145-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39115013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}