Wu Yang, Yuan Tan, Wang Wei-Wei, Ge Peng-Lei, Gao Zhi-Qiang, Zhang Gong, Tang Zhe, Dang Xiao-Wei, Zhao Yong-Fu, Zhang Jian-Ying, Jiang Guo-Zhong
Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou,
Department of Respiratory, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Cell Physiol Biochem. 2018;51(1):301-314. doi: 10.1159/000495231. Epub 2018 Nov 19.
BACKGROUND/AIMS: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway.
HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively.
The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group.
These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.
背景/目的:本研究旨在通过激活JAK2-STAT3信号通路,探讨长链非编码RNA HOST2(LncRNA HOST2)对肝癌(HCC)细胞上皮-间质转化(EMT)、增殖、侵袭和迁移的影响。
收集136例肝癌患者的肝癌组织和癌旁组织。采用免疫组织化学法检测JAK2和STAT3的表达。将肝癌SMMC7721细胞分为空白组、阴性对照组(NC)、HOST2模拟物组和HOST2抑制剂组。分别采用逆转录-定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法检测组织和细胞中HOST2、JAK2、STAT3、E-钙黏蛋白、波形蛋白、Snail、Slug、Twist和Zeb1的mRNA和蛋白表达水平。分别采用MTT法、划痕试验和Transwell试验检测细胞增殖、迁移和侵袭能力。
与癌旁组织相比,肝癌组织中JAK2、STAT3和波形蛋白水平较高,而E-钙黏蛋白表达较低。沉默HOST2可显著降低细胞增殖、迁移和侵袭能力,降低HOST2、JAK2、STAT3和波形蛋白水平,提高E-钙黏蛋白表达。沉默HOST2还可降低Snail、Slug和Twist水平,但增加Zeb1蛋白水平,而在HOST2模拟物组中观察到相反的结果。
这些结果揭示了肝癌中一种可能的机制,即LncRNA HOST2可能通过激活JAK2-STAT3信号通路增加EMT并增强肝癌细胞的增殖、侵袭和转移。