Zheng Yingjie, Zhang Jingyu, Ye Bin
Department of Gastroenterology, Lianshui County People's Hospital, Huai'an, China.
Department of Gastroenterology, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
Clin Exp Pharmacol Physiol. 2020 Mar;47(3):459-465. doi: 10.1111/1440-1681.13205. Epub 2019 Nov 25.
Cholangiocarcinoma is an aggressive malignancy with rapid invasion, metastasis and poor prognosis, however, the mechanism mediating its cholangiocarcinoma development needs further investigation. Here, we demonstrate that decreased miR-138 in tumor tissues is related to the poor prognosis in patients, and that miR-138 mediates sorafenib-induced cell survival in cholangiocarcinoma cells. Moreover, miR-138 negatively regulates SOX4 expression by specifically targeting its 3' untranslated region (3' UTR). As per our results, overexpression of SOX4 reversed sorafenib-induced changes in cell viability and apoptosis. Furthermore, the elevated levels of SOX4 in the tumor tissues that correlated with poor prognosis. Overall, the present study reveals that miR-138/SOX4 is involved in sorafinib-mediated cell survival in cholangiocarcinoma cells, and is associated with poor prognosis.
胆管癌是一种侵袭性恶性肿瘤，具有快速侵袭、转移且预后较差的特点，然而，介导其胆管癌发展的机制仍需进一步研究。在此，我们证明肿瘤组织中miR-138表达降低与患者预后不良相关，且miR-138介导索拉非尼诱导胆管癌细胞的存活。此外，miR-138通过特异性靶向SOX4的3'非翻译区（3'UTR）负向调节SOX4的表达。根据我们的结果，SOX4的过表达逆转了索拉非尼诱导的细胞活力和凋亡变化。此外，肿瘤组织中SOX4水平升高与预后不良相关。总体而言，本研究揭示miR-138/SOX4参与索拉非尼介导的胆管癌细胞存活，且与预后不良相关。
