| 冀 强,檀碧波,刘文博,等.miR-579-3p/ MYLK通路在胃癌细胞凋亡中的作用及机制[J].肿瘤学杂志,2026,32(2):127-133. |
| miR-579-3p/ MYLK通路在胃癌细胞凋亡中的作用及机制 |
| The Role and Mechanism of MiR-579-3p/ MYLK Pathway in the Apoptosis of Gastric Cancer Cells |
| 投稿时间：2025-03-25 |
| DOI：10.11735/j.issn.1671-170X.2026.02.B006 |
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| 中文关键词: 胃肿瘤 miR-579-3p 肌球蛋白轻链激酶 凋亡 凋亡基因 生物信息学 |
| 英文关键词:gastric neoplasms miR-579-3p myosin light chain kinase apoptosis apoptosis gene bioinformatics |
| 基金项目:河北省重点研发计划项目（22377701D）；河北省医学科学研究课题计划（20210886） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨微小RNA-579-3p（microRNA-579-3p，miR-579-3p）及其靶基因肌球蛋白轻链激酶（myosin light chain kinase，MYLK）在胃癌细胞凋亡调控中的作用及相关分子机制。［方法］ 利用癌症基因组图谱（The Cancer Genome Atlas，TCGA） 数据库，采用生物信息学方法分析miR-579-3p的表达及其功能。收集2022年1月至2022年6月河北医科大学第四医院40例初诊胃癌患者胃癌组织及相应癌旁组织。实时荧光定量PCR检测miR-579-3p及相关基因表达水平。应用miR-579-3p抑制物转染人胃癌细胞株HGC-27；CCK-8法检测细胞活性；流式细胞术检测细胞凋亡率；Western blot检测凋亡相关基因蛋白的表达。双荧光素酶报告基因分析验证miR-579-3p直接调控的基因。［结果］ 生物信息学及临床病例分析结果均显示，胃癌组织中miR-579-3p表达水平明显高于癌旁组织（P<0.05）。各胃癌细胞株（MKN45、AGS、NCIN87、HGC-27）中miR-579-3p表达水平均高于正常胃上皮细胞株GES-1（P均<0.05）），其中HGC-27中的miR-579-3p表达水平最高。功能富集分析发现miR-579-3p与血管生成、参与调解Hippo信号通路、细胞形态变化等多种生物学过程及通路有关。MYLK在肿瘤组织中表达低于癌旁组织（P<0.001），MYLK与miR-579-3p表达呈负相关。除MKN45外，其他各胃癌细胞株中MYLK水平均低于GES-1（P均<0.01）。在HGC-27细胞中，抑制miR-579-3p表达后MYLK表达增高（P<0.05）。双荧光素酶报告基因分析结果发现MYLK为miR-579-3p直接调控的基因。CCK-8和流式细胞术验证结果显示，抑制miR-579-3p表达可抑制细胞增殖（P<0.001）和促进肿瘤细胞凋亡（P<0.05）。转染miR-579-3p抑制物后HGC-27细胞中Bcl-2、Survivin的mRNA和蛋白表达均明显降低，而Bax 的mRNA和蛋白表达明显增高（P均<0.05）。［结论］ miR-579-3p能通过抑制MYLK表达，进而调节Bcl-2、Survivin、Bax等凋亡基因而参与胃癌细胞的凋亡过程。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate the role and molecular mechanisms of microRNA-579-3p (miR-579-3p) and its target gene myosin light chain kinase (MYLK) in the regulation of apoptosis in gastric cancer cells. ［Methods］ The expression and function of miR-579-3p was conducted by bioinformatics analysis. The expression levels of miR-579-3p and related genes was measured by quantitative real-time PCR. The human gastric cancer cell line HGC-27 was transfected with a miR-579-3p inhibitor. Cell viability was assessed by the CCK-8 assay， and apoptosis rates were determined by flow cytometry. The expression of apoptosis-related genes and proteins was detected by Western blot. Dual-luciferase reporter gene analysis was performed to validate the genes directly regulated by miR-579-3p. ［Results］ The results of bioinformatics and clinical case analysis showed that the expression level of miR-579-3p in gastric cancer tissues was significantly higher than that in paracancerous tissues (all P<0.05). The expression level of miR-579-3p in various gastric cancer cell lines (MKN45， AGS， NCIN87， HGC-27) was higher than that in normal gastric epithelial cell line GES-1 (all P<0.05)， with the highest expression observed in HGC-27 cells. Functional enrichment analysis revealed that miR-579-3p was associated with various biological processes and pathways such as blood vessel development， Hippo signaling， and cell morphogenesis. The expression level of MYLK in cancer tissues was lower than that in paracancerous tissues (P<0.001)， and MYLK was negatively correlated with miR-579-3p expression. Except for MKN45， the MYLK expression levels in all other gastric cancer cell lines were lower than in GES-1 (all P<0.01 ). Inhibition of miR-579-3p expression in HGC-27 cells led to increased MYLK expression (P<0.05). Dual-luciferase reporter gene analysis confirmed MYLK as a direct target of miR-579-3p. CCK-8 and flow cytometry assays demonstrated that inhibiting miR-579-3p expression suppressed cell proliferation (P<0.001) and promoted cancer cell apoptosis (P<0.05). Transfection with the miR-579-3p inhibitor significantly reduced the mRNA and protein expression of Bcl-2 and Survivin while increasing Bax (all P<0.05) in HGC-27 cells. ［Conclusion］ miR-579-3p participates in the apoptosis process of gastric cancer cells by inhibiting MYLK expression and subsequently regulating apoptosis-related genes such as Bcl-2， Survivin， and Bax. |
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