Zhuang L K, Yang Y T, Ma X, Han B, Wang Z S, Zhao Q Y, Wu L Q, Qu Z Q
Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Center for Medical Research, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Cell Death Dis. 2016 Apr 21;7(4):e2203. doi: 10.1038/cddis.2016.100.
MicroRNA (miRNA) and long non-coding RNA (lncRNA) have been demonstrated to participate in the progression of many cancers. Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors worldwide, while the molecular mechanisms underlying HCC tumorigenesis are not completely clear. In this study, we showed that miR-92b was significantly upregulated in tumor tissue and plasma of HCC patients, and its expression level was highly correlated with gender and microvascular invasion. Functionally, miR-92b could promote cell proliferation and metastasis of HCC in vitro and in vivo. Mechanistic investigations suggested that Smad7, which exhibited an inverse relationship with miR-92b expression in HCC, was a direct target of miR-92b and could reverse its effects on HCC tumorigenesis. Furthermore, long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and miR-92b could directly interact with and repress each other, and XIST could inhibit HCC cell proliferation and metastasis by targeting miR-92b. Taken together, our study not only revealed for the first time the importance of XIST/miR-92b/Smad7 signaling axis in HCC progression but also suggested the potential value of miR-92b as a biomarker in the clinical diagnosis and treatment of HCC.
微小RNA(miRNA)和长链非编码RNA(lncRNA)已被证明参与多种癌症的进展。肝细胞癌(HCC)是全球最常见且侵袭性最强的恶性肿瘤之一,然而HCC发生的分子机制尚不完全清楚。在本研究中,我们发现miR-92b在HCC患者的肿瘤组织和血浆中显著上调,其表达水平与性别和微血管侵犯高度相关。在功能上,miR-92b在体外和体内均可促进HCC的细胞增殖和转移。机制研究表明,在HCC中与miR-92b表达呈负相关的Smad7是miR-92b的直接靶标,并且可以逆转其对HCC发生的影响。此外,长链非编码RNA(lncRNA)X染色体失活特异性转录本(XIST)与miR-92b可直接相互作用并相互抑制,并且XIST可通过靶向miR-92b抑制HCC细胞增殖和转移。综上所述,我们的研究不仅首次揭示了XIST/miR-92b/Smad7信号轴在HCC进展中的重要性,还提示了miR-92b作为HCC临床诊断和治疗生物标志物的潜在价值。