Pub Date : 2024-01-01DOI: 10.2174/0113892037269589231017055642
Asmat Ullah, Anam Razzaq, Chuanzan Zhou, Najeeb Ullah, Somia Shehzadi, Tariq Aziz, Mohammad Y Alfaifi, Serag Eldin I Elbehairi, Haroon Iqbal
Eph receptors and their Eph receptor-interacting (ephrin) ligands comprise a vital cell communication system with several functions. In cancer cells, there was evidence of bilateral Eph receptor signaling with both tumor-suppressing and tumor-promoting actions. As a member of the Eph receptor family, EphB4 has been linked to tumor angiogenesis, growth, and metastasis, which makes it a viable and desirable target for drug development in therapeutic applications. Many investigations have been conducted over the last decade to elucidate the structure and function of EphB4 in association with its ligand ephrinB2 for its involvement in tumorigenesis. Although several EphB4-targeting drugs have been investigated, and some selective inhibitors have been evaluated in clinical trials. This article addresses the structure and function of the EphB4 receptor, analyses its possibility as an anticancer therapeutic target, and summarises knowledge of EphB4 kinase inhibitors. To summarise, EphB4 is a difficult but potential treatment option for cancers.
{"title":"Biological Significance of EphB4 Expression in Cancer.","authors":"Asmat Ullah, Anam Razzaq, Chuanzan Zhou, Najeeb Ullah, Somia Shehzadi, Tariq Aziz, Mohammad Y Alfaifi, Serag Eldin I Elbehairi, Haroon Iqbal","doi":"10.2174/0113892037269589231017055642","DOIUrl":"10.2174/0113892037269589231017055642","url":null,"abstract":"<p><p>Eph receptors and their Eph receptor-interacting (ephrin) ligands comprise a vital cell communication system with several functions. In cancer cells, there was evidence of bilateral Eph receptor signaling with both tumor-suppressing and tumor-promoting actions. As a member of the Eph receptor family, EphB4 has been linked to tumor angiogenesis, growth, and metastasis, which makes it a viable and desirable target for drug development in therapeutic applications. Many investigations have been conducted over the last decade to elucidate the structure and function of EphB4 in association with its ligand ephrinB2 for its involvement in tumorigenesis. Although several EphB4-targeting drugs have been investigated, and some selective inhibitors have been evaluated in clinical trials. This article addresses the structure and function of the EphB4 receptor, analyses its possibility as an anticancer therapeutic target, and summarises knowledge of EphB4 kinase inhibitors. To summarise, EphB4 is a difficult but potential treatment option for cancers.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Excessive insulin is the leading cause of metabolic syndromes besides hyperinsulinemia. Insulin-lowering therapeutic peptides have been poorly studied and warrant urgent attention.
Objectives: The main purpose of this study, was to introduce a novel peptide COX52-69 that was initially isolated from the porcine small intestine and possessed the ability to inhibit insulin secretion under high-glucose conditions by modulating large conductance Ca2+-activated K+ channels (BK channels) activity.
Methods and results: Enzyme-linked immunosorbent assay results indicate that COX52-69 supressed insulin release induced by high glucose levels in pancreatic islets and animal models. Furthermore, electrophysiological data demonstrated that COX52-69 can increase BK channel currents and hyperpolarize cell membranes. Thus, cell excitability decreased, corresponding to a reduction in insulin secretion.
Conclusion: Our study provides a novel approach to modulate high glucose-stimulated insulin secretion in patients with hyperinsulinemia.
{"title":"A Novel Peptide COX<sub>52-69</sub> Inhibits High Glucose-induced Insulin Secretion by Modulating BK Channel Activity.","authors":"Qian Lin, Jingtao Liu, Hengling Chen, Wenwu Hu, Weiqiong Lei, Meijie Wang, Xianguang Lin, Yongning Zhang, Huiting Ai, Su Chen, Chenhong Li","doi":"10.2174/0113892037249620231010063637","DOIUrl":"10.2174/0113892037249620231010063637","url":null,"abstract":"<p><strong>Background: </strong>Excessive insulin is the leading cause of metabolic syndromes besides hyperinsulinemia. Insulin-lowering therapeutic peptides have been poorly studied and warrant urgent attention.</p><p><strong>Objectives: </strong>The main purpose of this study, was to introduce a novel peptide COX<sub>52-69</sub> that was initially isolated from the porcine small intestine and possessed the ability to inhibit insulin secretion under high-glucose conditions by modulating large conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channels (BK channels) activity.</p><p><strong>Methods and results: </strong>Enzyme-linked immunosorbent assay results indicate that COX<sub>52-69</sub> supressed insulin release induced by high glucose levels in pancreatic islets and animal models. Furthermore, electrophysiological data demonstrated that COX<sub>52-69</sub> can increase BK channel currents and hyperpolarize cell membranes. Thus, cell excitability decreased, corresponding to a reduction in insulin secretion.</p><p><strong>Conclusion: </strong>Our study provides a novel approach to modulate high glucose-stimulated insulin secretion in patients with hyperinsulinemia.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54228129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0113892037265109231114065204
Sujatha M Hanumegowda, Chandramma Srinivasa, Ashwini Shivaiah, Manjula M Venkatappa, Rohith L Shankar, Ramesh K Lakshmaiah, Sathisha J Gonchigar, Devaraja Sannaningaiah
Background: Thrombosis is the key event that obstructs the flow of blood throughout the circulatory system, leading to stroke, myocardial infarction and severe cardiovascular complications. Currently, available antithrombotic drugs trigger several life-threatening side effects.
Introduction: Antithrombotic agents from natural sources devoid of adverse effects are grabbing high attention. In our previous study, we reported the antioxidant, anticoagulant and antiplatelet properties of kenaf seed protein extract. Therefore, in the current study, purification and characterization of cysteine protease from kenaf seed protein extract responsible for potential antithrombotic activity was undertaken.
Methods: Purification of KSCP (Kenaf Seed Cysteine Protease) was carried out using gel permeation and ion exchange column chromatography. The purity of the enzyme was evaluated by SDS PAGE (Sodium Dodecyl-Sulfate Polyacrylamide Gel Electrophoresis). RP-HPLC (Reverse Phase High-Performance Liquid Chromatography), MALDI-TOF (Matrix-Assisted Laser Desorption Ionization Time-Of-Flight) and CD (Circular Dichroism techniques) were employed for its characterization. Proteolytic, fibrinolytic and kinetic study was done using spectroscopy. Plasma recalcification time, Prothrombin Time (PT), Thrombin clotting time (TCT), Activated Partial Thromboplastin Time (APTT), bleeding time and platelet aggregation studies were carried out for antithrombotic activity of KSCP.
Result: A single sharp band of KSCP was observed under both reduced and non-reduced conditions, having a molecular mass of 24.1667kDa. KSCP was found to contain 30.3% helix turns and 69.7% random coils without a beta-pleated sheet. KSCP digested casein and fibrin, and its activity was inhibited by iodoacetic acid (IAA). KSCP was optimally active at pH 6.0 at the temperature of 40°C. KSCP exhibited anticoagulant properties by interfering in the intrinsic pathway of the blood coagulation cascade. Furthermore, KSCP dissolved both whole blood and plasma clots and platelet aggregation.
Conclusion: KSCP purified from kenaf seed extract showed antithrombotic potential. Hence, it could be a better candidate for the management of thrombotic complications.
{"title":"Kenaf Seed Cysteine Protease (KSCP) Inhibits the Intrinsic Pathway of the Blood Coagulation Cascade and Platelet Aggregation.","authors":"Sujatha M Hanumegowda, Chandramma Srinivasa, Ashwini Shivaiah, Manjula M Venkatappa, Rohith L Shankar, Ramesh K Lakshmaiah, Sathisha J Gonchigar, Devaraja Sannaningaiah","doi":"10.2174/0113892037265109231114065204","DOIUrl":"10.2174/0113892037265109231114065204","url":null,"abstract":"<p><strong>Background: </strong>Thrombosis is the key event that obstructs the flow of blood throughout the circulatory system, leading to stroke, myocardial infarction and severe cardiovascular complications. Currently, available antithrombotic drugs trigger several life-threatening side effects.</p><p><strong>Introduction: </strong>Antithrombotic agents from natural sources devoid of adverse effects are grabbing high attention. In our previous study, we reported the antioxidant, anticoagulant and antiplatelet properties of kenaf seed protein extract. Therefore, in the current study, purification and characterization of cysteine protease from kenaf seed protein extract responsible for potential antithrombotic activity was undertaken.</p><p><strong>Methods: </strong>Purification of KSCP (Kenaf Seed Cysteine Protease) was carried out using gel permeation and ion exchange column chromatography. The purity of the enzyme was evaluated by SDS PAGE (Sodium Dodecyl-Sulfate Polyacrylamide Gel Electrophoresis). RP-HPLC (Reverse Phase High-Performance Liquid Chromatography), MALDI-TOF (Matrix-Assisted Laser Desorption Ionization Time-Of-Flight) and CD (Circular Dichroism techniques) were employed for its characterization. Proteolytic, fibrinolytic and kinetic study was done using spectroscopy. Plasma recalcification time, Prothrombin Time (PT), Thrombin clotting time (TCT), Activated Partial Thromboplastin Time (APTT), bleeding time and platelet aggregation studies were carried out for antithrombotic activity of KSCP.</p><p><strong>Result: </strong>A single sharp band of KSCP was observed under both reduced and non-reduced conditions, having a molecular mass of 24.1667kDa. KSCP was found to contain 30.3% helix turns and 69.7% random coils without a beta-pleated sheet. KSCP digested casein and fibrin, and its activity was inhibited by iodoacetic acid (IAA). KSCP was optimally active at pH 6.0 at the temperature of 40°C. KSCP exhibited anticoagulant properties by interfering in the intrinsic pathway of the blood coagulation cascade. Furthermore, KSCP dissolved both whole blood and plasma clots and platelet aggregation.</p><p><strong>Conclusion: </strong>KSCP purified from kenaf seed extract showed antithrombotic potential. Hence, it could be a better candidate for the management of thrombotic complications.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/0113892037284176240302052521
Xin Wang, Qi Zhang, Yi Ren, Chao Liu, Huijie Gao
Preeclampsia (PE) is a serious pregnancy complication, and its primary clinical manifestations are gestational hypertension and proteinuria. Trophoblasts are responsible for the basic functions of the placenta during placental development; recent studies have revealed that placental "shallow implantation" caused by the decreased invasiveness of placental trophoblasts plays a crucial role in PE pathogenesis. The interaction between the cells and the extracellular matrix (ECM) plays a crucial role in trophoblast proliferation, differentiation, and invasion. Abnormal ECM function can result in insufficient migration and invasion of placental trophoblasts, thus participating in PE. This article summarizes the recent studies on the involvement of ECM components, including small leucine-rich proteoglycans, syndecans, glypicans, laminins, fibronectin, collagen, and hyaluronic acid, in the development of PE. ECM plays various roles in PE development, most notably by controlling the activities of trophoblasts. The ECM is structurally stable and can serve as a biological diagnostic marker and therapeutic target for PE.
子痫前期(PE)是一种严重的妊娠并发症,其主要临床表现为妊娠高血压和蛋白尿。滋养细胞在胎盘发育过程中担负着胎盘的基本功能;最近的研究发现,胎盘滋养细胞侵袭力下降导致的胎盘 "浅植入 "在子痫前期发病机制中起着至关重要的作用。细胞与细胞外基质(ECM)之间的相互作用在滋养细胞的增殖、分化和侵袭过程中起着至关重要的作用。ECM 功能异常可导致胎盘滋养细胞迁移和侵袭不足,从而参与 PE 的发生。本文总结了有关 ECM 成分(包括富含亮氨酸的小蛋白聚糖、辛迪加、糖蛋白、层粘连蛋白、纤连蛋白、胶原蛋白和透明质酸)参与 PE 发病的最新研究。ECM 在 PE 发育过程中发挥着各种作用,其中最主要的是控制滋养细胞的活动。ECM 结构稳定,可作为 PE 的生物诊断标记和治疗靶点。
{"title":"Research Progress on Extracellular Matrix Involved in the Development of Preeclampsia.","authors":"Xin Wang, Qi Zhang, Yi Ren, Chao Liu, Huijie Gao","doi":"10.2174/0113892037284176240302052521","DOIUrl":"10.2174/0113892037284176240302052521","url":null,"abstract":"<p><p>Preeclampsia (PE) is a serious pregnancy complication, and its primary clinical manifestations are gestational hypertension and proteinuria. Trophoblasts are responsible for the basic functions of the placenta during placental development; recent studies have revealed that placental \"shallow implantation\" caused by the decreased invasiveness of placental trophoblasts plays a crucial role in PE pathogenesis. The interaction between the cells and the extracellular matrix (ECM) plays a crucial role in trophoblast proliferation, differentiation, and invasion. Abnormal ECM function can result in insufficient migration and invasion of placental trophoblasts, thus participating in PE. This article summarizes the recent studies on the involvement of ECM components, including small leucine-rich proteoglycans, syndecans, glypicans, laminins, fibronectin, collagen, and hyaluronic acid, in the development of PE. ECM plays various roles in PE development, most notably by controlling the activities of trophoblasts. The ECM is structurally stable and can serve as a biological diagnostic marker and therapeutic target for PE.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.2174/1389203724666221221115630
Ting Li, Ruyue Wang, Kaike Li, Peiya Wang, Jiang Zhao, Qi Guo, Jun Zhang, Yang Li, Hongyu Li, Hui Yang
Background: Metastasis is the major cause of treatment failure in cancer patients and cancer- associated death, and an antimetastatic drug would be a beneficial therapy for cancer patients. HM-3-HSA is a fusion protein which improved the pharmacokinetics of HM-3 and exerted antitumor and anti-angiogenesis activity in multiple tumor models. However, the efficacy of HM-3-HSA in cancer cell migration and metastasis has not been elucidated.
Materials and methods: Herein, high-cell density fermentation of Pichiapink strain expressing HM- 3-HSA was performed for the first time. Then, the desired protein was purified by Butyl Sepharose High performance, Capto Blue, Phenyl Sepharose 6FF HS and DEAE Sepharose FF. Furthermore, the effect of HM-3-HSA on the migration and invasion of cancer cells was also evaluated, and B16F10 metastasis model was established to detected the anti- metastasis effect of HM-3-HSA in vivo.
Results: The results indicated that the yield of HM-3-HSA was 320 mg/L in a 10 L fermenter, which was a 46% increase over that expressed in flask cultivation. The desired protein was purified by fourstep, which yielded a 40% recovery of a product that had over 99% purity. Purified HM-3-HSA significantly suppressed the migration and invasion of HCT-116, SMMC-7721 and B16F10 cell lines.
Conclusion: On the other hand, in the B16F10 metastasis model, HM-3-HSA significantly inhibited pulmonary metastases of B16F10 cells, suggesting that HM-3-HSA exerted the anti-metastasis effect in vivo.
{"title":"Effectiveness of HM-3-HSA on Inhibiting Cancer Cell Migration and Metastasis.","authors":"Ting Li, Ruyue Wang, Kaike Li, Peiya Wang, Jiang Zhao, Qi Guo, Jun Zhang, Yang Li, Hongyu Li, Hui Yang","doi":"10.2174/1389203724666221221115630","DOIUrl":"https://doi.org/10.2174/1389203724666221221115630","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is the major cause of treatment failure in cancer patients and cancer- associated death, and an antimetastatic drug would be a beneficial therapy for cancer patients. HM-3-HSA is a fusion protein which improved the pharmacokinetics of HM-3 and exerted antitumor and anti-angiogenesis activity in multiple tumor models. However, the efficacy of HM-3-HSA in cancer cell migration and metastasis has not been elucidated.</p><p><strong>Materials and methods: </strong>Herein, high-cell density fermentation of Pichiapink strain expressing HM- 3-HSA was performed for the first time. Then, the desired protein was purified by Butyl Sepharose High performance, Capto Blue, Phenyl Sepharose 6FF HS and DEAE Sepharose FF. Furthermore, the effect of HM-3-HSA on the migration and invasion of cancer cells was also evaluated, and B16F10 metastasis model was established to detected the anti- metastasis effect of HM-3-HSA in vivo.</p><p><strong>Results: </strong>The results indicated that the yield of HM-3-HSA was 320 mg/L in a 10 L fermenter, which was a 46% increase over that expressed in flask cultivation. The desired protein was purified by fourstep, which yielded a 40% recovery of a product that had over 99% purity. Purified HM-3-HSA significantly suppressed the migration and invasion of HCT-116, SMMC-7721 and B16F10 cell lines.</p><p><strong>Conclusion: </strong>On the other hand, in the B16F10 metastasis model, HM-3-HSA significantly inhibited pulmonary metastases of B16F10 cells, suggesting that HM-3-HSA exerted the anti-metastasis effect in vivo.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.2174/1389203724666230307104135
Andrea Bernini, Ottavia Spiga, Annalisa Santucci
Alkaptonuria (AKU), a rare genetic disorder, is characterized by the accumulation of homogentisic acid (HGA) in organs, which occurs because the homogentisate 1,2-dioxygenase (HGD) enzyme is not functional due to gene variants. Over time, HGA oxidation and accumulation cause the formation of the ochronotic pigment, a deposit that provokes tissue degeneration and organ malfunction. Here, we report a comprehensive review of the variants so far reported, the structural studies on the molecular consequences of protein stability and interaction, and molecular simulations for pharmacological chaperones as protein rescuers. Moreover, evidence accumulated so far in alkaptonuria research will be re-proposed as the bases for a precision medicine approach in a rare disease.
{"title":"Structure-Function Relationship of Homogentisate 1,2-dioxygenase: Understanding the Genotype-Phenotype Correlations in the Rare Genetic Disease Alkaptonuria.","authors":"Andrea Bernini, Ottavia Spiga, Annalisa Santucci","doi":"10.2174/1389203724666230307104135","DOIUrl":"https://doi.org/10.2174/1389203724666230307104135","url":null,"abstract":"<p><p>Alkaptonuria (AKU), a rare genetic disorder, is characterized by the accumulation of homogentisic acid (HGA) in organs, which occurs because the homogentisate 1,2-dioxygenase (HGD) enzyme is not functional due to gene variants. Over time, HGA oxidation and accumulation cause the formation of the ochronotic pigment, a deposit that provokes tissue degeneration and organ malfunction. Here, we report a comprehensive review of the variants so far reported, the structural studies on the molecular consequences of protein stability and interaction, and molecular simulations for pharmacological chaperones as protein rescuers. Moreover, evidence accumulated so far in alkaptonuria research will be re-proposed as the bases for a precision medicine approach in a rare disease.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10219208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aims: The role of SNHG4 in the initiation and development of gastric cancer.
Background: Gastric cancer is one of the leading causes of cancer death worldwide. Studies have shown that lncRNAs have a regulatory function in human diseases, particularly cancers. Small nuclear RNA host gene 4 (SNHG4) has been known as an oncogenic long noncoding RNA (lncRNA) in various cancers, and its dysregulation can lead to tumorigenesis and cancer progression.
Objective: Alteration of SNHG4 expression in gastric cancer and its correlation with clinical features of patients with stomach cancer; also, the accomplishment of bioinformatic analysis to find the potential pathways which could be impressed by changes in SNHG4 RNA expression.
Methods: The present study aims to determine the molecular mechanism of SNHG4 and the effects of its expression on the development of GC. Based on the bioinformatics investigations, we studied gene expression analysis, Kaplan-Meier survival, Gene ontology (GO), KEGG pathway enrichment, microRNA targets, transcription factor targets, and proteins interacting with SNHG4. During the experimental phase, SNHG4 expression was examined by quantitative real-time PCR (qRTPCR) in 40 paired gastric adenocarcinoma tissues and normal neighboring tissues. Also, we investigated the correlation between SNHG4 expression and patients' clinicopathological characteristics.
Results: Increased SNHG4 expression was detected in GC tissues, which is significantly associated with the TNM stage, grade group, tumor size, and metastatic status. Evaluation survival analysis demonstrated that overexpression of SNHG4 in GC tissues is remarkably related to poor overall survival (OS). SNHG4 is closely related to miR-490 and E2F family transcription factors. GO analysis suggested the possible role of SNHG4 in cell-cell adhesion, and KEGG enrichment analysis revealed that SNHG4 could be associated with the gastric cancer signaling pathway. ELAVL1 and IGF2BP2 have the highest number of SNHG4 target sites, and these proteins are involved in the PI3K-Akt-mTOR and ERK-MAPK signaling pathways.
Conclusion: Based on our results, we conclude that SNHG4 may have a function in GC development by regulating tumor-related signaling pathways.
{"title":"Expression and Regulatory Roles of Small Nucleolar RNA Host Gene 4 in Gastric Cancer.","authors":"Navid Pourghasem, Shadi Ghorbanzadeh, Abdol Azim Nejatizadeh","doi":"10.2174/1389203724666230810094548","DOIUrl":"10.2174/1389203724666230810094548","url":null,"abstract":"<p><strong>Aims: </strong>The role of SNHG4 in the initiation and development of gastric cancer.</p><p><strong>Background: </strong>Gastric cancer is one of the leading causes of cancer death worldwide. Studies have shown that lncRNAs have a regulatory function in human diseases, particularly cancers. Small nuclear RNA host gene 4 (SNHG4) has been known as an oncogenic long noncoding RNA (lncRNA) in various cancers, and its dysregulation can lead to tumorigenesis and cancer progression.</p><p><strong>Objective: </strong>Alteration of SNHG4 expression in gastric cancer and its correlation with clinical features of patients with stomach cancer; also, the accomplishment of bioinformatic analysis to find the potential pathways which could be impressed by changes in SNHG4 RNA expression.</p><p><strong>Methods: </strong>The present study aims to determine the molecular mechanism of SNHG4 and the effects of its expression on the development of GC. Based on the bioinformatics investigations, we studied gene expression analysis, Kaplan-Meier survival, Gene ontology (GO), KEGG pathway enrichment, microRNA targets, transcription factor targets, and proteins interacting with SNHG4. During the experimental phase, SNHG4 expression was examined by quantitative real-time PCR (qRTPCR) in 40 paired gastric adenocarcinoma tissues and normal neighboring tissues. Also, we investigated the correlation between SNHG4 expression and patients' clinicopathological characteristics.</p><p><strong>Results: </strong>Increased SNHG4 expression was detected in GC tissues, which is significantly associated with the TNM stage, grade group, tumor size, and metastatic status. Evaluation survival analysis demonstrated that overexpression of SNHG4 in GC tissues is remarkably related to poor overall survival (OS). SNHG4 is closely related to miR-490 and E2F family transcription factors. GO analysis suggested the possible role of SNHG4 in cell-cell adhesion, and KEGG enrichment analysis revealed that SNHG4 could be associated with the gastric cancer signaling pathway. ELAVL1 and IGF2BP2 have the highest number of SNHG4 target sites, and these proteins are involved in the PI3K-Akt-mTOR and ERK-MAPK signaling pathways.</p><p><strong>Conclusion: </strong>Based on our results, we conclude that SNHG4 may have a function in GC development by regulating tumor-related signaling pathways.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.2174/138920372410231115093314
Stefania Galdiero, Massimiliano Galdiero, Carlo Pedone
The authors declare after the publication of the article entitled ‘β-Barrel Membrane Bacterial Proteins: Structure, Function, Assembly and Interaction with Lipids’’, published in Current Protein and Peptide Science, 2007, 8, 63-82 [1], that a reference by Koebnik was inadvertently omitted. The missing reference has now been included as: Original: