实用医学杂志 ›› 2021, Vol. 37 ›› Issue (17): 2176-2181.doi: 10.3969/j.issn.1006⁃5725.2021.17.002

• 基础研究 • 上一篇    下一篇

IRE1a与miR⁃346相互调节维持内质网应激强度促进宫颈癌细胞顺铂耐药

郭军飞,赖卫明马从利穆小萍   

  1. 广东省妇幼保健院检验科(广州 510000)

  • 出版日期:2021-09-10 发布日期:2021-09-10
  • 通讯作者: 穆小萍 E⁃mail:muxiaoping710@126.com
  • 基金资助:

    广东省自然基金资助项目(编号:2018A030310056


Mutual regulation of IRE1a and miR⁃346 promotes cisplatin resistances of cervical cancer cell via maintain⁃ ing edoplasmic reticulum stress strength

GUO Junfei,LAI Weiming,MA Congli,MU Xiaoping.   

  1. Department of Laboratory Medicine,Guangdong Woman and Children Hospital,Guangzhou 510000,China

  • Online:2021-09-10 Published:2021-09-10
  • Contact: MU Xiaoping E⁃mail:muxiaoping710@126.com

摘要:

目的 研究 IRE1a miR⁃346 相互调节维持内质网应激(edoplasmic reticulum stress,ERS 强度,在宫颈癌细胞顺铂耐药中的作用。方法 通过逐渐增加药物浓度的方法筛选顺铂耐药的宫颈癌细胞,通过基因芯片技术、实时荧光定量 PCR 技术、流式细胞术和双荧光素酶报告基因等方法检测顺 铂耐药宫颈癌细胞 miR⁃346、IRE1a 的表达情况,并验证 IRE1a⁃miR⁃346 相互调控及其在宫颈癌细胞顺 铂耐药中的作用。结果 相对亲本细胞,在顺铂耐药的宫颈癌细胞中存在基础水平的 ERS,ERS 通过 IRE1a 依赖的途径促进 miR⁃346 的表达,miR⁃346 参与宫颈癌细胞顺铂耐药;miR⁃346 通过靶定并下调 IRE1a 的表达维持顺铂耐药细胞 ERS 强度,抑制 IRE1a miR⁃125b 初始转录本的剪切,促进顺铂耐药细胞的存活。结论 IRE1a miR⁃346 相互调节,维持顺铂耐药细胞中 ERS 强度,促进宫颈癌细胞顺铂耐药。

关键词:

宫颈癌, 内质网应激, IRE1a, miR?346, 顺铂耐药

Abstract:

Objective To elucidate the role of mutual regulation of IRE1a and miR ⁃346 in maintaining ERS strength,and it′s role in cisplatin resistance of cervical cancer cells. Methods We screened cisplatin⁃resistant cervical cancer cells via gradually increasing the concentration of cisplatin,and detected the expression of IRE1a and miR⁃346 via gene array assay,quality PCR assay,flow cytometry assay and dual⁃luciferase reporter assay. We further validated the mutual regulation between IRE1a and miR⁃346,and its role in cispaltin resistance of cervical cancer cells. Results In contrast with the parental cervical cancer cells,there was a basic ERS in cisplatin resistant cells,and ERS enhanced the expression of miR⁃346 in IRE1a dependent manner which took part in the cisplatin resistant of cervical cancer cells. MiR⁃346 down⁃regulated the expression of IRE1a,which inhibited the degrada⁃ tion of pri⁃miR⁃125b,maintained the ERS strength in cisplatin⁃resistant cell and promoted cellular survival under cispaltin treatment. Conclusion Mutual regulation of IRE1a and miR⁃346 promotes cispaltin resistance of cervical cancer cells through maintaining ERS strength of cisplatin⁃resistant cells.

Key words:

cervical cancer, edoplasmic reticulum stress, IRE1a, miR?346, cisplatin resistance