miR-9靶向调控PTEN在HPV16+及HPV18+宫颈癌细胞凋亡中的作用

Role of miR-9-Targeted Regulation of PTEN in the Apoptosis of HPV16+ HPV18+ Cervical Cancer Cells

研究微小RNA-9(microRNA-9,miR-9)靶向调控人第10号染色体缺失的磷酸酶及张力蛋白同源蛋白(Recombinant phosphatase and tensin homolog,PTEN)在人乳头瘤病毒(Humanpa pilloma virus,HPV)16+及HPV18+宫颈癌细胞凋亡中的作用。收集宫颈癌组织及正常宫颈组织,培养HPV16+SiHa细胞、HPV18+HeLa细胞、HPV阴性C33A细胞及正常宫颈上皮H8细胞,检测miR-9、PTEN的表达水平。SiHa细胞和HeLa细胞进行分组转染后检测增殖抑制率、凋亡率、PTEN及miR-9表达水平。结果显示高危型HPV阳性及阴性的宫颈癌组织中miR-9的表达水平高于正常宫颈组织、PTEN的表达水平低于正常宫颈组织(P<0.05)且高危型HPV阳性宫颈癌组织中miR-9、PTEN表达的变化更显著;SiHa细胞、HeLa细胞中miR-9的表达水平高于C33A细胞和H8细胞、PTEN的表达水平低于C33A细胞和H8细胞(P<0.05);敲低miR-9表达后,SiHa细胞、HeLa细胞的PTEN表达水平、增殖抑制率、凋亡率均升高(P<0.05);敲低PTEN的表达削弱敲低miR-9表达的作用(P<0.05)。敲低miR-9通过增加PTEN表达的方式促进HPV16+及HPV18+宫颈癌细胞凋亡,miR-9靶向PTEN可能参与高危型HPV感染导致宫颈癌的发生。本研究通过临床样本检测及细胞实验初步揭示了miR-9靶向调控PTEN在高危型HPV感染导致宫颈癌发病的分子机制,在HPV感染的宫颈癌细胞中miR-9靶向抑制PTEN的表达并促进细胞增殖、抑制细胞凋亡,进而促进了肿瘤的发生发展。

We wished to study the role of microRNA(miR)-9-targeted regulation of phosphatase and tensin homolog(PTEN) in the apoptosis of human papillomavirus(HPV) 16 + and HPV18 + cervical cancer cells.Cervical cancer tissues and normal cervical tissues were collected. HPV16 + SiHa cells, HPV18 + HeLa cells, HPV-negative C33A cells and normal cervical epithelial H8 cells were cultured. Expression of miR-9 and PTEN was measured. SiHa cells and HeLa cells were divided into groups for transfection, and the inhibition of proliferation, apoptosis rate, PTEN expression, and miR-9 expression were measured. miR-9 expression in high-risk HPV-positive and-negative cervical cancer tissues was higher than that in normal cervical tissues, and PTEN expression was lower than that in normal cervical tissues(P<0.05). Expression of miR-9 and PTEN in high-risk HPV-positive cervical cancer was more significant. miR-9 expression in SiHa cells and HeLa cells was higher than that in C33A cells and H8 cells, and PTEN expression was lower than that in C33A cells and H8cells(P<0.05). After knockdown of miR-9 expression, we found that PTEN expression, inhibition of proliferation, and apoptosis rate of SiHa cells and HeLa cells increased(P<0.05). Knockdown of PTEN expression weakened the effect of knockdown of miR-9 expression. Our findings suggest that knockdown of miR-9 expression promotes the apoptosis of HPV16 + HPV18 + cervical cancer cells by increasing PTEN expression. miR-9-targeted regulation of PTEN may be involved in cervical cancer caused by high-risk HPV infection. We revealed(in a preliminary manner), using clinical samples and cell experiments, the molecular mechanism of miR-9-targeted regulation of PTEN in the pathogenesis of cervical cancer caused by high-risk HPV infection. In HPV-infected cervical cancer cells, miR-9-targeted inhibition of PTEN expression promoted cell proliferation and inhibited apoptosis to promote the occurrence and development of cervical cancer.