miR-17-5p通过下调BRMS1L表达调控鼻咽癌CNE2细胞增殖、侵袭、迁移和凋亡

miR-17-5p regulates proliferation, invasion, migration and apoptosis of nasopharyngeal carcinoma CNE2 cells by down-regulating BRMS1L expression

目的:探讨miR-17-5p通过调控乳腺癌转移抑制基因1相似基因(breast cancer metastasis suppressor 1 like,BRMS1-like或BRMS1L)表达调控鼻咽癌细胞增殖和侵袭的分子机制。方法:收集2014年1月至2017年12月间平煤神马医疗集团总医院收治的40例鼻咽癌患者切除的鼻咽癌组织及其相应的癌旁组织标本,以及鼻咽癌细胞系CNE 2、HONE 1、C666-1和鼻咽部永生化上皮细胞株NP69,采用qPCR检测miR-17-5p在癌组织和癌细胞系中的表达水平。通过StarBase数据库预测BRMS1L与miR-17-5p的靶向关系,采用双荧光素酶报告基因实验进行验证。WB检测转染miR-17-5p模拟物和抑制物对CNE2细胞中BRMS1L表达的影响;CCK-8、Transwell和流式细胞术检测miR-17-5p/BRMS1L分子轴对CNE2细胞增殖、侵袭、迁移和凋亡的影响。结果:miR-17-5p在鼻咽癌组织和鼻咽癌细胞系中呈高表达(P<0.05或P<0.01),下调miR-17-5p显著抑制CNE2细胞增殖、侵袭、迁移但促进细胞凋亡(P<0.05或P<0.01)。miR-17-5p靶向作用于BRMS1L并下调其表达水平。过表达BRMS1L可显著抑制CNE2细胞增殖、侵袭、迁移而促进细胞凋亡(均P<0.01);而同时过表达miR-17-5p和BRMS1L可逆转上述作用(均P<0.01)。结论:miR-17-5p通过靶向下调BRMS1L的表达,进而促进CNE2细胞增殖、侵袭和迁移而抑制细胞凋亡。

Objective: To explore the molecular mechanism of miR-17-5 p regulating the proliferation and invasion of nasopharyngeal carcinoma cells by regulating the expression of breast cancer metastasis suppressor 1 like(BRMS1-like or BRMS1 L) gene. Methods: A total of 40 cases of nasopharyngeal carcinoma tissues and corresponding paracancerous tissues resected from nasopharyngeal carcinoma patients, who were admitted to the General Hospital of Pingdingshan Shenma Medical Group during January 2014 to December 2017, were included in this study;in addition, nasopharyngeal carcinoma cell lines CNE 2, HONE 1, C666-1 and nasopharyngeal immortalized epithelial cell line NP69 were also collected for this study. The expression of mi R-17-5 p in nasopharyngeal carcinoma tissues and cell lines was detected by qPCR. The targeted relationship between BRMS1 L and miR-17-5 p was predicted by the StarBase and verified by the Dual luciferase reporter gene assay. Effects of transfection of mi R-17-5 p mimics and inhibitors on the expression of BRMS1 L in CNE2 cells were detected by WB assay. CCK-8, Transwell and Flow cytometry were used to detect the effects of miR-17-5 p/BRMS1 L axis on the proliferation,migration, invasion and apoptosis of CNE 2 cells. Results: mi R-17-5 p was highly expressed in nasopharyngeal carcinoma tissues and cell lines(P<0.05 or P<0.01). Knockdown of mi R-17-5 p significantly inhibited proliferation, invasion and migration of CNE2 cells but promoted apoptosis(P<0.05 or P<0.01);mi R-17-5 p targeted BRMS1 Land down-regulated its expression. Over-expression of BRMS1 L significantly inhibited the proliferation, invasion and migration of CNE2 cells but promoted apoptosis(all P<0.01);while simultaneous over-expression of mi R-17-5 p and BRMS1 L reversed the above effects(all P<0.01). Conclusion: mi R-17-5 p promoted proliferation, invasion, migration and inhibited apoptosis of CNE 2 cells by down-regulating the expression of BRMS1 L.