Zhou Xi, Yue Yan, Wang Renxiao, Gong Baolan, Duan Zhao
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Department of Obstetrics and Gynecology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Int J Oncol. 2017 Mar;50(3):853-862. doi: 10.3892/ijo.2017.3857. Epub 2017 Jan 19.
MicroRNA (miR)-145 has been reported to induce cancer stem cell (CSC) differentiation through down-regulation of the stem cell transcription factors (TFs) that maintain CSC pluripotency. High expression of miR-145 indicates a good prognosis in cancer patients, but its role in cervical cancer stem cells (CCSCs) is not known. We show that expression of miR-145 and core stem cell transcription factors, Sox2, Nanog and Oct4, are associated with the pluripotency of CCSCs, with increased expression of miR-145 after cervical tumorsphere (CT) differentiation. miR-145 overexpression inhibited expression of core TFs, as well as decreasing tumor invasion and colony formation, whereas miR-145 knockdown led to the opposite effects. Injection of adenovirus-miR-145 significantly reduced tumor growth in nude mice. High miR-145 expression predicted a better prognosis compared with that in patients with low miR-145 expression after analyses of The Cancer Genome Atlas (TCGA) data. These results suggest that miR-145 is able to induce CT differentiation through enzymolyzing TFs and might be a therapeutic target for cervical carcinoma.
据报道，微小RNA（miR）-145通过下调维持癌症干细胞（CSC）多能性的干细胞转录因子（TF）来诱导癌症干细胞分化。miR-145的高表达表明癌症患者预后良好，但其在宫颈癌干细胞（CCSC）中的作用尚不清楚。我们发现，miR-145与核心干细胞转录因子Sox2、Nanog和Oct4的表达与CCSC的多能性相关，在宫颈肿瘤球（CT）分化后miR-145表达增加。miR-145过表达抑制了核心TF的表达，同时减少了肿瘤侵袭和集落形成，而miR-145敲低则产生相反的效果。注射腺病毒-miR-145可显著降低裸鼠肿瘤生长。分析癌症基因组图谱（TCGA）数据后发现，与miR-145低表达患者相比，miR-145高表达预示着更好的预后。这些结果表明，miR-145能够通过酶解TF诱导CT分化，可能是宫颈癌的一个治疗靶点。
