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中国癌症防治杂志

中国癌症防治杂志 ›› 2023, Vol. 15 ›› Issue (3): 263-271.doi: 10.3969/j.issn.1674-5671.2023.03.03

• 基础研究 • 上一篇    下一篇

piR⁃hsa⁃130912促进上皮性卵巢癌细胞增殖、侵袭与迁移及其作用机制

  

  1. 广西医科大学附属肿瘤医院妇科肿瘤科；区域性高发肿瘤早期防治研究教育部重点实验室（广西医科大学）；广西医科大学附属肿瘤医院心肺功能中心
  • 出版日期:2023-06-25 发布日期:2023-06-19
  • 通讯作者: 阳志军 E-mail：yzj7528@126.com
  • 基金资助:
    区域性高发肿瘤早期防治研究教育部重点实验室自主课题（GKE?ZZ202018；GKE?ZZ202121）；广西医学高层次骨干人才培养“139”项目（201414；201822）；广西“新世纪十百千人才工程”项目专项基金（2014210）；广西壮族自治区临床重点专科建设项目（2018?39）

The role and mechanism of piR-hsa-130912 in promoting proliferation,invasion and migration ofepithelial ovarian cancer cells

  • Online:2023-06-25 Published:2023-06-19

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摘要： 目的 探讨piR⁃hsa⁃130912对上皮性卵巢癌（epithelial ovarian cancer, EOC）细胞增殖、侵袭及迁移的调控作用及其分子机制。方法 通过对EOC组织进行BGISEQ UMI Small RNA测序以及RT⁃qPCR检测，鉴定出piR⁃hsa⁃130912。用LV⁃piR⁃hsa⁃130912⁃up、piR⁃hsa⁃130912⁃inhibitor及相应阴性对照慢病毒感染EOC细胞A2780和SKOV3以干扰piR⁃hsa⁃130912表达水平，采用CCK⁃8、平板克隆实验检测细胞的增殖能力，Transwell侵袭、迁移实验及划痕实验检测细胞的侵袭及迁移能力，Western blot检测肿瘤转移相关蛋白zeb⁃1、E⁃cadherin以及vimentin的表达水平。结合RNA测序、GSEA分析、KEGG及GO分析初步探索piR⁃hsa⁃130912调控EOC细胞增殖、侵袭及迁移的作用机制。结果 BGISEQ UMI Small RNA测序和RT⁃qPCR验证结果显示，piR⁃hsa⁃130912在EOC组织中高表达。与相应阴性对照组比较，过表达piR⁃hsa⁃130912可增强A2780和SKOV3细胞的增殖、侵袭及迁移能力（均P<0.05），促进A2780细胞中zeb⁃1及vimentin的蛋白表达（P=0.020, 0.017）并抑制E⁃cadherin的表达（P<0.001）；抑制piR⁃hsa⁃130912表达可导致A2780和SKOV3细胞的增殖、侵袭及迁移能力减弱（均P<0.05），促进SKOV3细胞中E⁃cadherin的表达（P=0.005）并抑制vimentin的表达（P=0.015）。piR⁃hsa⁃130912可能参与花生四烯酸代谢、亚油酸代谢、MAPK等癌症相关信号通路以及受体酪氨酸激酶信号传导途径的调节。结论 piR⁃hsa⁃130912可促进EOC细胞增殖、侵袭及迁移，其作用机制可能与脂质代谢、MAPK等癌症相关信号通路的调节相关。

关键词: 上皮性卵巢癌, piRNA, 增殖, 侵袭, 迁移

Abstract: Objective To investigate the role of piR⁃hsa⁃130912 on the proliferation, invasion and migration of epithelial ovarian cancer(EOC) cells  and its molecular mechanism. Methods BGISEQ UMI Small RNA sequencing and RT⁃qPCR were performed to identify piR⁃hsa⁃130912 in EOC tissues. LV⁃piR⁃hsa⁃130912⁃up, piR⁃hsa⁃130912⁃inhibitor and corresponding negative control virus were used to infect EOC cells A2780 and SKOV3 and interfere with the expression level of piR⁃hsa⁃130912. Cell proliferation was detected by CCK⁃8 and clone formation assays. Cells invasion and migration abilities were determined by Transwell assay and wound healing experiment. Western blot was used to examine the expression of tumor metastasis⁃related proteins zeb⁃1, E⁃cadherin and vimentin. The mechanism of piR⁃hsa⁃130912 regulating cell proliferation, invasion and migration was preliminarily explored by combining RNA sequencing, GSEA analysis, KEGG and GO analyses. Results BGISEQ UMI Small RNA sequencing and RT⁃qPCR results confirmed that piR⁃hsa⁃130912 was highly expressed in EOC tissues. Compared to the corresponding negative control group, overexpression of piR⁃hsa⁃130912 enhanced the proliferation, invasion and migration of A2780 and SKOV3 cells (all P<0.05), and promoted the protein expression of zeb⁃1 and vimentin in A2780 cells (P=0.020, 0.017), while inhibited the expression of E⁃cadherin (P<0.001). Additionally, inhibition of piR⁃hsa⁃130912 expression weakened the proliferation, invasion, and migration abilities of A2780 and SKOV3 cells (all P<0.05), and promoted the expression of E⁃cadherin in SKOV3 cells (P=0.005), while inhibited the expression of vimentin (P=0.015). Moreover, piR⁃hsa⁃130912 could be involved in the regulation of arachidonic acid metabolism, linoleic acid metabolism, MAPK signaling pathway and receptor tyrosine kinase. Conclusions piR⁃hsa⁃130912 could promote the proliferation, invasion and migration of EOC cells, and its mechanism may be related to the regulation of lipid metabolism, MAPK and other tumor⁃related signaling pathways.

Key words: Epithelial ovarian cancer, piRNA, Proliferation, Invasion, Migration

中图分类号: 

  • R737.31