Zhou Huading, Guo Weijie, Zhao Yingjun, Wang Yifei, Zha Ruopeng, Ding Jie, Liang Linhui, Yang Guanghua, Chen Zongyou, Ma Baojin, Yin Baobing
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Cancer Sci. 2014 Aug;105(8):956-65. doi: 10.1111/cas.12463.
The precise functions and mechanisms of microRNAs (miR) in gallbladder cancer (GBC) remain elusive. In this study, we found that miR-135a-5p expression is often dampened and correlated with neoplasm histologic grade in GBC. MicroRNA-135a-5p introduction clearly inhibited GBC cell proliferation in vitro and in vivo. Moreover, very low density lipoprotein receptor (VLDLR), which is often upregulated in GBC tissues, was identified as a direct functional target of miR-135a-5p. Furthermore, the p38 MAPK pathway was proven to be involved in miR-135a-VLDLR downstream signaling. Together, these results suggested that the miR-135a-VLDLR-p38 axis may contribute to GBC cell proliferation.
微小RNA（miR）在胆囊癌（GBC）中的精确功能和机制仍不清楚。在本研究中，我们发现miR-135a-5p的表达常常受到抑制，且与GBC的肿瘤组织学分级相关。引入MicroRNA-135a-5p明显抑制了GBC细胞在体外和体内的增殖。此外，在GBC组织中经常上调的极低密度脂蛋白受体（VLDLR）被确定为miR-135a-5p的直接功能靶点。此外，p38丝裂原活化蛋白激酶（MAPK）通路被证明参与了miR-135a-VLDLR的下游信号传导。总之，这些结果表明miR-135a-VLDLR-p38轴可能促进GBC细胞增殖。
