Zhu Dandan, Yuan Donglan, Guo Runfa, Zhang Lixin, Guo Ting, Zhao Yinling, Wang Jia, Chen Xinping, Qian Hua, Ge Hongshan
Department of Obstetrics and Gynecology, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China.
Central Laboratory, Taizhou People's Hospital, Fifth Affiliated Hospital to Nantong University, Taizhou, Jiangsu 225300, P.R. China.
Oncol Lett. 2019 Jul;18(1):402-410. doi: 10.3892/ol.2019.10321. Epub 2019 May 6.
Decreased expression of microRNA (miR)-148a is associated with poor prognosis in ovarian cancer. The aim of the present study was to investigate the impact of miR-148a on tumor cell viability and invasion via targeting forkhead box protein O3 (FOXO3). Expression of miR-148a was detected in paired tumor and adjacent normal tissues. OVCAR3 cells were transfected with miR-148a mimic and inhibitor. Cell viability, apoptosis and invasion were determined. A luciferase reporter assay was used to study the association between miR-148a and FOXO3. In addition, the influence of miR-148a on tumor cell growth was investigated by performing xenograft assays in nude mice. RT-qPCR showed that miR-148a was downregulated in ovarian cancer tissues. Overexpression of miR-148a in OVCAR3 cells inhibited cell viability, suppressed invasion and promoted cellular apoptosis. The dual-luciferase assay indicated that miR-148a directly regulated the expression of FOXO3, a transcription factor of caspase-3. Western blotting confirmed that the expression of caspase-3 was regulated by the modulation of miR-148a expression. assays revealed that miR-148a overexpression inhibited the growth of OVCAR3 ×enograft tumors in nude mice. miR-148a is a tumor suppressor in ovarian cancer OVCAR3 cells and in nude mice. The suppressive effect is due to inhibiting cell viability and invasion as well as promoting apoptosis. These results may provide theoretical basis for targeting miR-148a in the treatment of ovarian cancer.
微小RNA(miR)-148a表达降低与卵巢癌预后不良相关。本研究旨在探讨miR-148a通过靶向叉头框蛋白O3(FOXO3)对肿瘤细胞活力和侵袭的影响。在配对的肿瘤组织和相邻正常组织中检测miR-148a的表达。用miR-148a模拟物和抑制剂转染OVCAR3细胞。测定细胞活力、凋亡和侵袭情况。采用荧光素酶报告基因检测法研究miR-148a与FOXO3之间的关系。此外,通过在裸鼠中进行异种移植试验研究miR-148a对肿瘤细胞生长的影响。RT-qPCR显示miR-148a在卵巢癌组织中表达下调。OVCAR3细胞中miR-148a的过表达抑制细胞活力、抑制侵袭并促进细胞凋亡。双荧光素酶检测表明miR-148a直接调节caspase-3的转录因子FOXO3的表达。蛋白质印迹证实caspase-3的表达受miR-148a表达调节的影响。试验表明miR-148a过表达抑制裸鼠中OVCAR3异种移植肿瘤的生长。miR-148a是卵巢癌OVCAR3细胞和裸鼠中的肿瘤抑制因子。其抑制作用是由于抑制细胞活力和侵袭以及促进凋亡。这些结果可能为以miR-148a为靶点治疗卵巢癌提供理论依据。