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EPHA5 enhances stemness and decreases gefitinib sensitivity via Wnt signaling pathway in non-small lung cancer
IF 2 Q3 ONCOLOGY
Advances in cancer biology - metastasis
Pub Date : 2025-02-16 DOI: 10.1016/j.adcanc.2025.100135
Jie Li , Yehan Zhu

Objective

Non-small lung cancer (NSCLC) is the most prevalent form of lung cancer, and it is often associated with poor patient outcomes. Erythropoietin-producing hepatocellular receptor A5 (EPHA5), a member of the Eph tyrosine kinase receptor family, has been implicated in various stages of tumor progression. However, the specific role of EPHA5 in NSCLC remains poorly understood. This study aims to explore the influence of EPHA5 on the stemness of NSCLC cancer cells and their sensitivity to gefitinib, while also investigating the underlying mechanisms involved.

Methods

EPHA5 expression was suppressed using small interfering ribonucleic acids (siRNAs), while qPCR and Western blot were applied to analyze the knockdown efficiency. Subsequently, the expressions of stem cell-related markers, such as SOX2, Nanog, KLF4, Oct4, and β-catenin, were detected and quantified via qPCR and Western blot during the experiment, while CD133-positive cells were analyzed via flow cytometry. Gefitinib sensitivity was evaluated in EPHA5-knockdown cells. The Wnt activator, CHIR-99021, was employed to rescue β-catenin expression.

Results

EPHA5 expression was elevated in NSCLC cell lines (NCI-H460 and NCI-H1229) but considerably downregulated by siRNAs. EPHA5 knockdown alleviated stemness, enhanced gefitinib sensitivity, and suppressed Wnt activation, as evidenced by lower CD133-positive cells, and decreased expression of Sox2, Nanog, KLF4, Oct4, and β-catenin. The Wnt activator reversed the inhibitory effect of EPHA5 on cancer cell stemness by upregulating β-catenin.

Conclusion

Silencing the expression of EPHA5 can reduce NSCLC stemness and enhance gefitinib sensitivity by inhibiting the Wnt signaling pathway.

Strengths and limitations of this study

We find EPHA5 enhances stemness and decreases gefitinib sensitivity via Wnt signaling pathway of non-small cell lung cancer but prognostic follow-up of lung adenocarcinoma patients in this study is lacking.
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引用次数: 0
Silencing of long non-coding RNAs MIR22HG, LNCTAM34A, and TP53TG1 triggers cell survival/proliferation and inhibits apoptosis in women's breast cancer
IF 2 Q3 ONCOLOGY
Advances in cancer biology - metastasis
Pub Date : 2025-02-05 DOI: 10.1016/j.adcanc.2025.100133
Ahmed Al-Kateb , Roozbeh Heidarzadehpilehrood , Maryam Pirhoushiaran , Rasoul Abdollahzadeh , Mojtaba Saffari , Keivan Majidzadeh-A , Sepideh Mehrpoor Layeghi , Mohammad Hossein Modarressi

Background

This study investigated the functional and translational role of long non-coding RNAs (lncRNAs), specifically MIR22HG, LNCTAM34A, and TP53TG1, in breast cancer (BC).

Methods

The expression of the lncRNAs was measured using RT-qPCR. Knockdown experiments using siRNA were conducted in breast cancer cell lines (MDA-MB-231, MDA-MB-453, and MCF-7) to assess the functional impact of silencing these lncRNAs. Cell proliferation, colony formation, invasion, migration, and apoptosis assays were performed to evaluate phenotypic changes.

Results

The expression of MIR22HG, LNCTAM34A, and TP53TG1 was significantly decreased in tumor tissues compared to NATs (p < 0.05). Lower expression of these lncRNAs correlated with advanced TNM stage and grade groups (p < 0.05). MIR22HG was overexpressed in the BC cell lines MDA-MB-231 and MCF-7, while LNCTAM34A and TP53TG1 were upregulated in MDA-MB-453 and MCF-7 BC cell lines. Silencing these lncRNAs led to a significant increase in cell proliferation, colony formation, invasion, and migration (p < 0.001). Additionally, apoptosis was significantly decreased in cells with silenced lncRNAs (p < 0.05). Knockdown of MIR22HG, LNCTAM34A, and TP53TG1 in BC cells resulted in increased cell proliferation and colony formation. Silencing of these lncRNAs significantly increased cell migration and invasion. The silencing of MIR22HG, LNCTAM34A, and TP53TG1 decreased apoptosis in BC cells.

Conclusion

Study demonstrates that MIR22HG, LNCTAM34A, and TP53TG1 function as tumor suppressors in breast cancer. Downregulation of these lncRNAs promotes tumor progression by enhancing cell proliferation, invasion, and migration, while inhibiting apoptosis.
{"title":"Silencing of long non-coding RNAs MIR22HG, LNCTAM34A, and TP53TG1 triggers cell survival/proliferation and inhibits apoptosis in women's breast cancer","authors":"Ahmed Al-Kateb ,&nbsp;Roozbeh Heidarzadehpilehrood ,&nbsp;Maryam Pirhoushiaran ,&nbsp;Rasoul Abdollahzadeh ,&nbsp;Mojtaba Saffari ,&nbsp;Keivan Majidzadeh-A ,&nbsp;Sepideh Mehrpoor Layeghi ,&nbsp;Mohammad Hossein Modarressi","doi":"10.1016/j.adcanc.2025.100133","DOIUrl":"10.1016/j.adcanc.2025.100133","url":null,"abstract":"<div><h3>Background</h3><div>This study investigated the functional and translational role of long non-coding RNAs (lncRNAs), specifically MIR22HG, LNCTAM34A, and TP53TG1, in breast cancer (BC).</div></div><div><h3>Methods</h3><div>The expression of the lncRNAs was measured using RT-qPCR. Knockdown experiments using siRNA were conducted in breast cancer cell lines (MDA-MB-231, MDA-MB-453, and MCF-7) to assess the functional impact of silencing these lncRNAs. Cell proliferation, colony formation, invasion, migration, and apoptosis assays were performed to evaluate phenotypic changes.</div></div><div><h3>Results</h3><div>The expression of MIR22HG, LNCTAM34A, and TP53TG1 was significantly decreased in tumor tissues compared to NATs (<em>p</em> &lt; 0.05). Lower expression of these lncRNAs correlated with advanced TNM stage and grade groups (<em>p</em> &lt; 0.05). MIR22HG was overexpressed in the BC cell lines MDA-MB-231 and MCF-7, while LNCTAM34A and TP53TG1 were upregulated in MDA-MB-453 and MCF-7 BC cell lines. Silencing these lncRNAs led to a significant increase in cell proliferation, colony formation, invasion, and migration (<em>p</em> &lt; 0.001). Additionally, apoptosis was significantly decreased in cells with silenced lncRNAs (<em>p</em> &lt; 0.05). Knockdown of MIR22HG, LNCTAM34A, and TP53TG1 in BC cells resulted in increased cell proliferation and colony formation. Silencing of these lncRNAs significantly increased cell migration and invasion. The silencing of MIR22HG, LNCTAM34A, and TP53TG1 decreased apoptosis in BC cells.</div></div><div><h3>Conclusion</h3><div>Study demonstrates that MIR22HG, LNCTAM34A, and TP53TG1 function as tumor suppressors in breast cancer. Downregulation of these lncRNAs promotes tumor progression by enhancing cell proliferation, invasion, and migration, while inhibiting apoptosis.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"13 ","pages":"Article 100133"},"PeriodicalIF":2.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dysregulated key long non-coding RNAs TP53TG1, RFPL1S, DLEU1, and HCG4 associated with epithelial-mesenchymal transition (EMT) in castration-resistant prostate cancer
IF 2 Q3 ONCOLOGY
Advances in cancer biology - metastasis
Pub Date : 2025-01-25 DOI: 10.1016/j.adcanc.2025.100132
Tahmineh Mehrabi , Roozbeh Heidarzadehpilehrood , Meysam Mobasheri , Tabassom Sobati , Masoumeh Heshmati , Maryam Pirhoushiaran

Background

Castration-resistant prostate cancer (CRPC) is the severe and metastatic form of prostate cancer and demands effective, reliable diagnostic and therapeutic approaches. It has been shown that long non-coding RNAs (lncRNAs) dysregulations promote metastasis in tumors. The current research aim is to identify dysregulated lncRNAs in metastatic CRPC.

Materials and methods

R programs along with multiple packages were applied to identify novel lncRNAs dysregulated in CRPC. Raw data of clinical samples were obtained from NCBI-GSE74685, which consisted of metastatic and non-metastatic CRPC samples, and was analyzed through a limma package of R with defined cutoff criteria as adjusted P-value < 0.05 and |Fold Change = FC| ≥ ±1. To further understand lncRNA co-expression gene modules, WGCNA analysis, hub-gene identification, and pathway enrichment were performed.

Results

Four dysregulated lncRNAs were identified with more than a two-fold change in expression levels, including TP53TG1, RFPL1S, DLEU1, and HCG4. WGCNA analysis results in royal blue, salmon, light cyan, and blue co-expression modules with dysregulated lncRNAs. According to a pathway enrichment study, these co-expressed modules showed enrichment in highly relevant pathways to the CRPC metastatic process, including mesenchymal-to-epithelial transition, purine metabolism, C-MYB transcription factor network, and immune system. In addition, SOD2, PRKCA, IL6, and ITGAM were identified as hub genes.

Conclusion

The current study suggests dysregulation of TP53TG1, RFPL1S, DLEU1, and HCG4 lncRNAs and corresponding hub genes may promote CRPC metastasis through the EMT pathways.
{"title":"Dysregulated key long non-coding RNAs TP53TG1, RFPL1S, DLEU1, and HCG4 associated with epithelial-mesenchymal transition (EMT) in castration-resistant prostate cancer","authors":"Tahmineh Mehrabi ,&nbsp;Roozbeh Heidarzadehpilehrood ,&nbsp;Meysam Mobasheri ,&nbsp;Tabassom Sobati ,&nbsp;Masoumeh Heshmati ,&nbsp;Maryam Pirhoushiaran","doi":"10.1016/j.adcanc.2025.100132","DOIUrl":"10.1016/j.adcanc.2025.100132","url":null,"abstract":"<div><h3>Background</h3><div>Castration-resistant prostate cancer (CRPC) is the severe and metastatic form of prostate cancer and demands effective, reliable diagnostic and therapeutic approaches. It has been shown that long non-coding RNAs (lncRNAs) dysregulations promote metastasis in tumors. The current research aim is to identify dysregulated lncRNAs in metastatic CRPC.</div></div><div><h3>Materials and methods</h3><div>R programs along with multiple packages were applied to identify novel lncRNAs dysregulated in CRPC. Raw data of clinical samples were obtained from NCBI-GSE74685, which consisted of metastatic and non-metastatic CRPC samples, and was analyzed through a limma package of R with defined cutoff criteria as adjusted <em>P-value</em> &lt; 0.05 and |Fold Change = FC| ≥ ±1. To further understand lncRNA co-expression gene modules, WGCNA analysis, hub-gene identification, and pathway enrichment were performed.</div></div><div><h3>Results</h3><div>Four dysregulated lncRNAs were identified with more than a two-fold change in expression levels, including TP53TG1, RFPL1S, DLEU1, and HCG4. WGCNA analysis results in royal blue, salmon, light cyan, and blue co-expression modules with dysregulated lncRNAs. According to a pathway enrichment study, these co-expressed modules showed enrichment in highly relevant pathways to the CRPC metastatic process, including mesenchymal-to-epithelial transition, purine metabolism, C-MYB transcription factor network, and immune system. In addition, SOD2, PRKCA, IL6, and ITGAM were identified as hub genes.</div></div><div><h3>Conclusion</h3><div>The current study suggests dysregulation of TP53TG1, RFPL1S, DLEU1, and HCG4 lncRNAs and corresponding hub genes may promote CRPC metastasis through the EMT pathways.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"13 ","pages":"Article 100132"},"PeriodicalIF":2.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143151537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Upregulation of mitochondrial function is associated with advanced prostate cancer 线粒体功能的上调与晚期前列腺癌有关
IF 2 Q3 ONCOLOGY
Advances in cancer biology - metastasis
Pub Date : 2024-11-26 DOI: 10.1016/j.adcanc.2024.100131
Valentin Baumgartner , Thomas Paul Scherer , Ashkan Mortezavi , Niels Rupp , Holger Moch , Peter Wild , Susanne Dettwiler , Miriam Wanner , Dominik Enderlin , Souzan Salemi , Daniel Eberli

Background

The mitochondrial metabolism in prostate cancer (PCa) is of great importance due the unique metabolic shift from glycolysis to oxidative phosphorylation. In this study, we aimed to analyze the expression level of mitochondrial markers TOM20, DRP1 and OPA1 in benign and malignant tissue, to assess if these markers are associated with different grade and stage of PCa.

Materials and methods

This study assessed TOM20, DRP1, and OPA1 expression in formalin-fixed, paraffin-embedded prostate tissue samples, including benign and malignant tissue specimen. Immunohistochemistry on tissue microarrays was conducted, with staining intensities scored semi-quantitatively. Statistical analyses evaluated associations with PCa grade and stage. A survival analysis for biochemical recurrence (RFS), overall survival (OS) and disease specific survival (DSS) was performed using multivariate Cox regression analysis to assess prognostic properties of the markers.

Results

In total, 527 patients were included in our analysis, which composed of 45 (8.5 %) benign prostate hyperplasia (BPH) and 482 (91.5 %) PCa samples (436 localized (90.5 %) and 46 (9.5 %) metastatic). Immunoreactivity for TOM20, DRP1 and OPA1 was strong in 2 of 43 (4.7 %), 1 of 43 (2.3 %) and 0 of 43 (0 %) of BPH control tissue. Strong marker expression was significantly increased in radical prostatectomy specimen (TOM20: 111/371 (29.9 %), DRP1: 89/373 (23.9 %), OPA1: 60/371 (16.2 %), p < 0.001) and in metastatic tissue (TOM20: 22/42 (52.4 %), DRP1: 14/42 (33.3 %), OPA1: 21/41 (51.2 %), p < 0.001). None of the markers demonstrated prognostic properties for RFS, OS, and DSS.

Conclusion

A strong association between the expression of the mitochondrial markers TOM20, DRP1 and OPA1 and PCa aggressiveness was demonstrated. However, these markers were not found to be prognostic regarding RFS, OS and DSS. Future studies are needed focusing on the underlying mechanisms of the upregulation of mitochondrial metabolism in aggressive PCa and evaluate potential therapeutic implications.
前列腺癌（PCa）的线粒体代谢从糖酵解到氧化磷酸化的独特代谢转变具有重要意义。在本研究中，我们旨在分析线粒体标志物TOM20、DRP1和OPA1在良恶性组织中的表达水平，以评估这些标志物是否与不同级别和分期的PCa相关。材料和方法本研究检测了福尔马林固定、石蜡包埋前列腺组织标本（包括良性和恶性组织标本）中TOM20、DRP1和OPA1的表达。对组织微阵列进行免疫组化，对染色强度进行半定量评分。统计分析评估与前列腺癌分级和分期的关系。采用多变量Cox回归分析对生化复发（RFS）、总生存（OS）和疾病特异性生存（DSS）进行生存分析，以评估标志物的预后特性。结果共纳入527例患者，其中良性前列腺增生45例（8.5%），前列腺癌482例（91.5%），局限性前列腺增生436例（90.5%），转移性前列腺增生46例（9.5%）。43例BPH对照组织中2例（4.7%）、1例（2.3%）和0例（0%）的TOM20、DRP1和OPA1的免疫反应性较强。强标记物表达在根治性前列腺切除术标本中显著升高(TOM20: 111/371 (29.9%), DRP1: 89/373 (23.9%), OPA1: 60/371 (16.2%), p <；0.001)和转移组织(TOM20: 22/42 (52.4%), DRP1: 14/42 (33.3%), OPA1: 21/41 (51.2%), p <；0.001)。没有任何标志物显示RFS、OS和DSS的预后特性。结论线粒体标记TOM20、DRP1和OPA1的表达与前列腺癌侵袭性密切相关。然而，这些标志物对RFS、OS和DSS没有预测作用。未来的研究需要关注侵袭性前列腺癌中线粒体代谢上调的潜在机制，并评估潜在的治疗意义。
{"title":"Upregulation of mitochondrial function is associated with advanced prostate cancer","authors":"Valentin Baumgartner ,&nbsp;Thomas Paul Scherer ,&nbsp;Ashkan Mortezavi ,&nbsp;Niels Rupp ,&nbsp;Holger Moch ,&nbsp;Peter Wild ,&nbsp;Susanne Dettwiler ,&nbsp;Miriam Wanner ,&nbsp;Dominik Enderlin ,&nbsp;Souzan Salemi ,&nbsp;Daniel Eberli","doi":"10.1016/j.adcanc.2024.100131","DOIUrl":"10.1016/j.adcanc.2024.100131","url":null,"abstract":"<div><h3>Background</h3><div>The mitochondrial metabolism in prostate cancer (PCa) is of great importance due the unique metabolic shift from glycolysis to oxidative phosphorylation. In this study, we aimed to analyze the expression level of mitochondrial markers TOM20, DRP1 and OPA1 in benign and malignant tissue, to assess if these markers are associated with different grade and stage of PCa.</div></div><div><h3>Materials and methods</h3><div>This study assessed TOM20, DRP1, and OPA1 expression in formalin-fixed, paraffin-embedded prostate tissue samples, including benign and malignant tissue specimen. Immunohistochemistry on tissue microarrays was conducted, with staining intensities scored semi-quantitatively. Statistical analyses evaluated associations with PCa grade and stage. A survival analysis for biochemical recurrence (RFS), overall survival (OS) and disease specific survival (DSS) was performed using multivariate Cox regression analysis to assess prognostic properties of the markers.</div></div><div><h3>Results</h3><div>In total, 527 patients were included in our analysis, which composed of 45 (8.5 %) benign prostate hyperplasia (BPH) and 482 (91.5 %) PCa samples (436 localized (90.5 %) and 46 (9.5 %) metastatic). Immunoreactivity for TOM20, DRP1 and OPA1 was strong in 2 of 43 (4.7 %), 1 of 43 (2.3 %) and 0 of 43 (0 %) of BPH control tissue. Strong marker expression was significantly increased in radical prostatectomy specimen (TOM20: 111/371 (29.9 %), DRP1: 89/373 (23.9 %), OPA1: 60/371 (16.2 %), <em>p</em> &lt; 0.001) and in metastatic tissue (TOM20: 22/42 (52.4 %), DRP1: 14/42 (33.3 %), OPA1: 21/41 (51.2 %), <em>p</em> &lt; 0.001). None of the markers demonstrated prognostic properties for RFS, OS, and DSS.</div></div><div><h3>Conclusion</h3><div>A strong association between the expression of the mitochondrial markers TOM20, DRP1 and OPA1 and PCa aggressiveness was demonstrated. However, these markers were not found to be prognostic regarding RFS, OS and DSS. Future studies are needed focusing on the underlying mechanisms of the upregulation of mitochondrial metabolism in aggressive PCa and evaluate potential therapeutic implications.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"13 ","pages":"Article 100131"},"PeriodicalIF":2.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect of pDNA-Buforin II on the expression changes of lncRNAs PCA3, PCAT1, PRNCR1, GAS5 in prostate cancer pDNA-Buforin II 对前列腺癌中 lncRNA PCA3、PCAT1、PRNCR1、GAS5 表达变化的影响
IF 2 Q3 ONCOLOGY
Advances in cancer biology - metastasis
Pub Date : 2024-10-30 DOI: 10.1016/j.adcanc.2024.100130
Fatemeh Dehkhodaei , Abbas Doosti

Background

This work aims to analyze the alterations in the levels of PCA3, PCAT1, PRNCR1, and GAS5 long non-coding RNAs (lncRNAs) after the activation of pDNA-buforin II in PC3 cancer cells.

Materials and methods

The synthetic nucleic acid sequence of buforin II was included in the pcDNA3.1(+) Mammalian Expression Plasmid. The accuracy of cloning was assessed by using PCR and enzyme digestion techniques. The vectors were transfected into cells utilizing LipofectamineTM2000. The PC3 cancer cells were evaluated using flow cytometry and wound healing analysis. The expression levels of lncRNAs and apoptotic genes were assessed utilizing real-time PCR, with a significance threshold of P < 0.05.

Results

The recombinant plasmid containing the pDNA-buforin II vector was successfully generated, and the gene sequence demonstrated complete uniformity (100 % similarity) with the buforin II gene. The transfection efficiency of PC3 cells was 79 %. The results are quantified utilizing the growth inhibition 50 % (GI50) parameter, representing the concentration of pDNA-buforin II required to halt 50 % of cell growth. The percentages of early apoptosis, late apoptosis, necrosis, and viable PC3 cells in the pDNA-buforin II group were 23.30 %, 12.70 %, 3.9 %, and 60.10 %, respectively. The RT-PCR study demonstrated that the presence of pDNA-buforin II in PC3 cells decreased the transcription of PCA3, PCAT1, and PRNCR1 lncRNAs compared to the control group treated with PBS. Furthermore, it enhanced the transcription of GAS5 lncRNA. The findings demonstrated a significant upregulation of transcription factors in programmed cell death after treatment with pDNA-buforin II (∗∗P < 0.01).

Conclusions

According to the results of this study, it can be inferred that pDNA-buforin II can modify the transcription of genes in PC3 cancer cells, specifically about lncRNAs involved in cell apoptotic pathways. The pDNA-buforin II molecule has promising anticancer capabilities and can trigger apoptosis in cells.
背景本研究旨在分析 pDNA-buforin II 激活 PC3 癌细胞后 PCA3、PCAT1、PRNCR1 和 GAS5 长非编码 RNA（lncRNA）水平的变化。利用 PCR 和酶切技术评估了克隆的准确性。利用 LipofectamineTM2000 将载体转染到细胞中。使用流式细胞仪和伤口愈合分析对 PC3 癌细胞进行评估。结果pDNA-buforin II载体重组质粒成功产生，其基因序列与buforin II基因完全一致（100%相似）。PC3 细胞的转染效率为 79%。转染结果用生长抑制 50%（GI50）参数进行量化，该参数代表阻止 50% 细胞生长所需的 pDNA-buforin II 浓度。pDNA-buforin II 组早期凋亡、晚期凋亡、坏死和存活 PC3 细胞的百分比分别为 23.30%、12.70%、3.9% 和 60.10%。RT-PCR 研究表明，与用 PBS 处理的对照组相比，pDNA-buforin II 在 PC3 细胞中的存在降低了 PCA3、PCAT1 和 PRNCR1 lncRNA 的转录。此外，它还增强了 GAS5 lncRNA 的转录。结论根据本研究的结果，可以推断 pDNA-buforin II 可以改变 PC3 癌细胞中基因的转录，特别是参与细胞凋亡通路的 lncRNA。pDNA-buforin II 分子具有很好的抗癌能力，能引发细胞凋亡。
{"title":"The effect of pDNA-Buforin II on the expression changes of lncRNAs PCA3, PCAT1, PRNCR1, GAS5 in prostate cancer","authors":"Fatemeh Dehkhodaei ,&nbsp;Abbas Doosti","doi":"10.1016/j.adcanc.2024.100130","DOIUrl":"10.1016/j.adcanc.2024.100130","url":null,"abstract":"<div><h3>Background</h3><div>This work aims to analyze the alterations in the levels of <em>PCA3</em>, <em>PCAT1</em>, <em>PRNCR1</em>, and <em>GAS5</em> long non-coding RNAs (lncRNAs) after the activation of pDNA-buforin II in PC3 cancer cells.</div></div><div><h3>Materials and methods</h3><div>The synthetic nucleic acid sequence of buforin II was included in the pcDNA3.1(+) Mammalian Expression Plasmid. The accuracy of cloning was assessed by using PCR and enzyme digestion techniques. The vectors were transfected into cells utilizing LipofectamineTM2000. The PC3 cancer cells were evaluated using flow cytometry and wound healing analysis. The expression levels of lncRNAs and apoptotic genes were assessed utilizing real-time PCR, with a significance threshold of P &lt; 0.05.</div></div><div><h3>Results</h3><div>The recombinant plasmid containing the pDNA-buforin II vector was successfully generated, and the gene sequence demonstrated complete uniformity (100 % similarity) with the buforin II gene. The transfection efficiency of PC3 cells was 79 %. The results are quantified utilizing the growth inhibition 50 % (GI50) parameter, representing the concentration of pDNA-buforin II required to halt 50 % of cell growth. The percentages of early apoptosis, late apoptosis, necrosis, and viable PC3 cells in the pDNA-buforin II group were 23.30 %, 12.70 %, 3.9 %, and 60.10 %, respectively. The RT-PCR study demonstrated that the presence of pDNA-buforin II in PC3 cells decreased the transcription of <em>PCA3</em>, <em>PCAT1</em>, and <em>PRNCR1</em> lncRNAs compared to the control group treated with PBS. Furthermore, it enhanced the transcription of <em>GAS5</em> lncRNA. The findings demonstrated a significant upregulation of transcription factors in programmed cell death after treatment with pDNA-buforin II (∗∗P &lt; 0.01).</div></div><div><h3>Conclusions</h3><div>According to the results of this study, it can be inferred that pDNA-buforin II can modify the transcription of genes in PC3 cancer cells, specifically about lncRNAs involved in cell apoptotic pathways. The pDNA-buforin II molecule has promising anticancer capabilities and can trigger apoptosis in cells.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"12 ","pages":"Article 100130"},"PeriodicalIF":2.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ZNF775 inhibits MCF-7 breast cancer cell migration by downregulating Wnt5a ZNF775 通过下调 Wnt5a 抑制 MCF-7 乳腺癌细胞迁移
IF 2 Q3 ONCOLOGY
Advances in cancer biology - metastasis
Pub Date : 2024-10-25 DOI: 10.1016/j.adcanc.2024.100129
Wei Gong , Xin Zhu , Wenwu Zhang , Xiaoyu Song , Junjie Hu , Weihua Xu , Zhichao Ma , Bin Xiao , Linhai Li , Xinping Chen
C2H2 zinc finger protein is widely involved in the occurrence and development of cancer. However, the function and mechanism of most C2H2 zinc finger proteins in breast caner (BC) remains unclear. Here, we reported the expression prognosis of C2H2 type zinc finger protein ZNF775 in BC patients and its possible biological mechanism. First, multiple public databases showed that ZNF775 was significantly overexpressed in BC tissues. Interestingly, high expression of ZNF775 was significantly associated with a better prognosis. Immunohistochemistry were used for verification, and the expression of ZNF775 was consistent with the databases. Considering the large heterogeneity of different breast cancer cells, we temporarily selected MCF-7 cell line for verification. In vitro overexpression experiments showed that overexpression of ZNF775 significantly inhibited the proliferation and migration of MCF-7 BC cell. We further combined RNA-sequencing (RNA-seq) and CUT & Tag, and found that overexpression of ZNF775 can down-regulate the expression of most genes in the Wnt signaling pathway. The cBioportal database showed that ZNF775 was negatively correlated with the expression of Wnt5a, suggesting that its downstream target was likely Wnt5a. Finally, we discovered that Wnt5a could partially reverse the inhibitory effect of ZNF775 on MCF-7 BC cell migration through transwell migration experiments. In conclusion, our findings will provide new ideas for the diagnosis, treatment and prognosis assessment of BC in the future.
C2H2 锌指蛋白广泛参与癌症的发生和发展。然而，大多数 C2H2 型锌指蛋白在乳腺癌（BC）中的功能和机制仍不清楚。在此，我们报告了C2H2型锌指蛋白ZNF775在乳腺癌患者中的表达预后及其可能的生物学机制。首先，多个公共数据库显示ZNF775在BC组织中显著过表达。有趣的是，ZNF775的高表达与较好的预后明显相关。免疫组化法进行了验证，ZNF775的表达与数据库一致。考虑到不同乳腺癌细胞的异质性较大，我们暂时选择 MCF-7 细胞系进行验证。体外过表达实验表明，过表达 ZNF775 能显著抑制 MCF-7 BC 细胞的增殖和迁移。我们进一步结合 RNA 序列分析（RNA-seq）和 CUT & Tag，发现过表达 ZNF775 可下调 Wnt 信号通路中大部分基因的表达。cBioportal数据库显示，ZNF775与Wnt5a的表达呈负相关，表明其下游靶标可能是Wnt5a。最后，我们通过经孔迁移实验发现，Wnt5a 可以部分逆转 ZNF775 对 MCF-7 BC 细胞迁移的抑制作用。总之，我们的研究结果将为今后 BC 的诊断、治疗和预后评估提供新的思路。
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引用次数: 0
Niosomes containing enciprazine hydrochloride have been shown to efficiently inhibit the proliferation and induce apoptosis in colorectal cancer cells 含有盐酸安非拉嗪的 Niosomes 已被证明能有效抑制结直肠癌细胞的增殖并诱导其凋亡
IF 2 Q3 ONCOLOGY
Advances in cancer biology - metastasis
Pub Date : 2024-09-17 DOI: 10.1016/j.adcanc.2024.100128
Hosain Nasirian , Saeedeh TarvijEslami , Hedieh Ghourchian , Marjaneh Ebrahimi , Tohid Piri-Gharaghie , Ghazal Ghajari

Colorectal cancer (CRC), currently the second most widespread cancer globally, exhibits a higher incidence in young individuals. Advancements have been made in developing anti-colorectal cancer drugs, including cytotoxic chemicals, in the past few decades. There is a need for new and innovative medications to overcome the current challenges in cancer treatment. Recent research examined the efficacy of innovative formulations in the prevention of colorectal cancer. In this study, we evaluated the efficacy of a niosome formulation loaded with Enciprazine hydrochloride (Nio-USAN). We assessed the anti-colorectal cancer characteristics of Nio-USAN by employing several techniques including CCK-8, invasion test, MTT test, flow cytometry, and cell cycle assessment. Quantitative real-time PCR was utilized to assess the transcription of genes linked to apoptosis. The F1-Nio-USAN and F2-Nio-USAN have average sizes of 200 and 500 nm, respectively. The entrapment effectiveness (EE%) of the F1-Nio-USAN and F2-Nio-USAN was measured to be 85.32 ± 0.27 % and 87.12 ± 0.35 %, respectively. The F1-Nio-USAN group exhibited the following percentages of HT-29 cell states: 43 % early apoptosis, 21 % late apoptosis, 7 % necrotic, and 29 % viable. The levels of transcription for cas8, Bid, BAX, cas9, and cas3 were significantly elevated in the treatment groups as compared to the PBS control group (P < 0.001). In addition, the treatment group exhibited significantly reduced levels of BCL2 gene transcription compared to the PBS control group (P < 0.01). These results suggest that it may be possible to improve the efficacy of USAN formulations in combating cancer by utilizing noisome encapsulation.

大肠癌（CRC）是目前全球第二大最常见的癌症，在年轻人中发病率较高。过去几十年来，抗结直肠癌药物（包括细胞毒性化学品）的研发取得了进展。目前需要新的创新药物来应对癌症治疗中的挑战。最近的研究考察了创新制剂在预防结直肠癌方面的疗效。在本研究中，我们评估了含盐酸恩西普嗪的niosome制剂（Nio-USAN）的疗效。我们采用多种技术评估了 Nio-USAN 的抗结直肠癌特性，包括 CCK-8、侵袭试验、MTT 试验、流式细胞术和细胞周期评估。实时定量 PCR 被用来评估与细胞凋亡相关的基因转录。F1-Nio-USAN 和 F2-Nio-USAN 的平均尺寸分别为 200 纳米和 500 纳米。据测定，F1-Nio-USAN 和 F2-Nio-USAN 的夹带效率（EE%）分别为 85.32 ± 0.27 % 和 87.12 ± 0.35 %。F1-Nio-USAN 组的 HT-29 细胞状态百分比如下：早期凋亡占 43%，晚期凋亡占 21%，坏死占 7%，存活占 29%。与 PBS 对照组相比，治疗组 cas8、Bid、BAX、cas9 和 cas3 的转录水平明显升高（P < 0.001）。此外，与 PBS 对照组相比，治疗组的 BCL2 基因转录水平明显降低（P <0.01）。这些结果表明，利用噪音体封装技术可以提高 USAN 制剂的抗癌功效。
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引用次数: 0
Navigating the interplay between BCL-2 family proteins, apoptosis, and autophagy in colorectal cancer 探索结直肠癌中 BCL-2 家族蛋白、细胞凋亡和自噬之间的相互作用
IF 2 Q3 ONCOLOGY
Advances in cancer biology - metastasis
Pub Date : 2024-07-26 DOI: 10.1016/j.adcanc.2024.100126
Amanda Shen-Yee Kong , Sathiya Maran , Hwei-San Loh

Colorectal cancer (CRC) remains a significant global health challenge, with an alarming upward trend in Asia. Early detection is crucial for improving outcomes, but there is no consensus on the optimal screening approach. Despite advances in diagnosis and therapy, CRC mortality rates remain substantial. Apoptosis and autophagy, key processes in cancer cell death, exhibit complex molecular crosstalk, particularly involving BH-3-only proteins, which present potential therapeutic targets. Recent studies suggest that manipulating these pathways could enhance cancer treatment by exploiting their regulatory networks. The B-cell lymphoma 2 (BCL-2) family proteins, central to apoptosis regulation, are implicated in CRC initiation, progression, and therapy resistance. BH3-only proteins like BIM and PUMA are linked to caspase-independent cell death, suggesting alternative pathways for CRC treatment and highlighting the potential for targeted therapies. This review provides an overview of CRC management, including the current landscape and challenges of screening programs and delves into the interplay between apoptosis and autophagy in CRC cell death. It emphasizes the critical role of BCL-2 family proteins in CRC pathogenesis and calls for future research to focus on developing non-invasive, cost-effective diagnostic biomarkers, establishing prognostic biomarker panels, and defining predictive biomarkers for existing treatments. These advancements are essential for improving screening strategies, therapeutic interventions, and ultimately, patient outcomes and quality of life.

结直肠癌（CRC）仍然是全球健康面临的重大挑战，在亚洲有惊人的上升趋势。早期发现对于改善预后至关重要，但对于最佳筛查方法尚未达成共识。尽管在诊断和治疗方面取得了进步，但 CRC 的死亡率仍然很高。癌细胞死亡的关键过程--细胞凋亡和自噬表现出复杂的分子串扰，特别是涉及纯 BH-3 蛋白质，而这些蛋白是潜在的治疗靶点。最近的研究表明，操纵这些通路可以利用它们的调控网络来提高癌症治疗效果。B 细胞淋巴瘤 2（BCL-2）家族蛋白是细胞凋亡调控的核心，与 CRC 的发生、发展和耐药性有关。BIM 和 PUMA 等纯 BH3 蛋白与不依赖于 Caspase 的细胞死亡有关，为 CRC 治疗提供了替代途径，并凸显了靶向疗法的潜力。本综述概述了 CRC 的治疗，包括筛查项目的现状和挑战，并深入探讨了 CRC 细胞死亡中细胞凋亡和自噬之间的相互作用。它强调了 BCL-2 家族蛋白在 CRC 发病机制中的关键作用，并呼吁未来的研究重点应放在开发无创、具有成本效益的诊断生物标记物、建立预后生物标记物面板以及确定现有治疗方法的预测性生物标记物上。这些进展对于改进筛查策略、治疗干预以及最终改善患者预后和生活质量至关重要。
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引用次数: 0
PD-L1 and PD-1 in immune regulation and their implications in blood cancers 免疫调节中的 PD-L1 和 PD-1 及其对血癌的影响
IF 2 Q3 ONCOLOGY
Advances in cancer biology - metastasis
Pub Date : 2024-07-25 DOI: 10.1016/j.adcanc.2024.100125
Parisa Shiri Aghbash , Faezeh Mehdizadeh , Ghazal Pourbeiragh , Yalda Yazdani , Hossein Bannazadeh Baghi , Abolfazl Jafari Sales , Mehrdad Pashazadeh , Parisa Kangari

Because of emerging opportunities for cancer immunotherapy, the capacity to suppress the immune system in order to cure and eradicate cancer is currently a topic of intense study. When the bone marrow microenvironment is exposed to immune suppression, leukemia cells result in the immune system's inability to eliminate malignant cells. To get a better understanding of the immunological possibilities associated with leukemia, clinical trials have explored immunotherapy techniques such as T cell activators, checkpoint inhibitors, antibody medicinal molecules, and cell treatments. One of the most important immune pathways is the programmed cell death 1 (PD1) protein. PD1 is expressed on the surface of T-cells and controls immune reactions. CD274, B7–H1, or PD-L1 are expressed by cells of the myeloid lineage, including macrophages, dendritic cells, effector CD8+ T cells, tumor cells, and tumor-associated suppressor cells. Expression of PD-L1 molecule in cancer has been associated to worse prognosis and resistance to anti-cancer therapies in several malignancies. In this review, we update on the expression of PD-1 molecule in malignant hematological tumor cells and describe these molecules which inhibit the immune response to cancer cells. We provide an overview of the current scientific advancements, the significance of immunotherapy strategies and highlighting the potential for further development in targeting this specific molecule. Additionally, ascertaining if PD-1/PD-L1 can be a reliable prognostic for blood cancer diagnosis.

由于癌症免疫疗法的机会不断涌现，抑制免疫系统以治愈和根除癌症的能力目前是一个热门研究课题。当骨髓微环境受到免疫抑制时，白血病细胞会导致免疫系统无法消除恶性细胞。为了更好地了解与白血病相关的免疫学可能性，临床试验探索了免疫疗法技术，如 T 细胞激活剂、检查点抑制剂、抗体药物分子和细胞疗法。程序性细胞死亡 1（PD1）蛋白是最重要的免疫途径之一。PD1 表达于 T 细胞表面，控制着免疫反应。CD274、B7-H1 或 PD-L1 由髓系细胞表达，包括巨噬细胞、树突状细胞、效应 CD8+ T 细胞、肿瘤细胞和肿瘤相关抑制细胞。在多种恶性肿瘤中，PD-L1 分子在癌症中的表达与预后恶化和抗癌疗法的耐药性有关。在这篇综述中，我们将介绍 PD-1 分子在恶性血液肿瘤细胞中的最新表达情况，并描述这些抑制癌细胞免疫反应的分子。我们概述了当前的科学进展、免疫疗法策略的意义，并强调了针对这一特定分子进一步开发的潜力。此外，我们还将确定 PD-1/PD-L1 是否可作为血癌诊断的可靠预后指标。
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引用次数: 0
Therapeutic potential of mesenchymal stem cells and its exosomes in colorectal cancer: Paving way from preclinical towards clinical road 间充质干细胞及其外泌体在结直肠癌中的治疗潜力：从临床前走向临床之路
IF 2 Q3 ONCOLOGY
Advances in cancer biology - metastasis
Pub Date : 2024-07-08 DOI: 10.1016/j.adcanc.2024.100123
Zunaira Ali Baig , Farzana Shafqat , Iffat Mushtaq , Ummara Aslam , Asma Faryal , Ayesha Maryam

Colorectal cancer is one of the most prevalent cancers worldwide. An increasing number of cases around the globe are raising concerns for life quality and survival. Various factors including genetic drivers have been extensively studied regarding the disease risk, progression, and metastasis. However, the signaling mechanisms haven't been studied extensively yet. Various therapeutic methods have been established in combating the disease, and mesenchymal stem cells have come up as a crucial cell-based therapeutic strategy. Mesenchymal stem cells have been regarded as potential targets in various cancer types due to their immune-modulatory functions. They can be isolated from many body tissues including bone marrow, peripheral blood, umbilical cord, and adipose tissue. Exosomes derived from mesenchymal stem cells have been reported to affect the expression of certain proteins associated with colorectal cancer. The current review highlights the potential of mesenchymal stem cells and their derived exosomes in treating cancer by causing cytotoxicity and apoptosis. Further, T-cell mediated modulation of exosomes helps reduce the cellular proliferation in cancer cells.

大肠癌是全球发病率最高的癌症之一。全球越来越多的病例引发了人们对生活质量和存活率的担忧。关于疾病风险、进展和转移，包括遗传因素在内的各种因素已被广泛研究。然而，信号传导机制尚未得到广泛研究。目前已建立了多种治疗方法来对抗这种疾病，而间充质干细胞已成为一种重要的细胞治疗策略。间充质干细胞因其免疫调节功能而被视为各种癌症的潜在靶点。它们可以从骨髓、外周血、脐带和脂肪组织等多种人体组织中分离出来。据报道，从间充质干细胞中提取的外泌体可影响与结直肠癌相关的某些蛋白质的表达。本综述强调了间充质干细胞及其衍生的外泌体通过引起细胞毒性和细胞凋亡治疗癌症的潜力。此外，T细胞介导的外泌体调节有助于减少癌细胞的细胞增殖。
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