Zhao Haiting, Peng Renjun, Liu Qing, Liu Dingyang, Du Peng, Yuan Jian, Peng Gang, Liao Yiwei
Department of Neurology, Xiangya Hospital, The Central South University (CSU), Changsha, 410008, PR China.
Department of Neurosurgery, Xiangya Hospital, The Central South University (CSU), Changsha, 410008, PR China.
Arch Biochem Biophys. 2016 Nov 15;610:1-7. doi: 10.1016/j.abb.2016.09.014. Epub 2016 Sep 28.
H19, one of the first found cancer-associated long non-coding RNAs (lncRNAs), is involved in the development and progression of many types of tumors. An aberrant expression of H19 was observed in hepatocellular carcinoma, cervical cancer, breast cancer, ovarian cancer, and colorectal cancer. However, the exact effects and molecular mechanisms of H19 in glioma progression are still unknown up to now. In this study, we investigated the role of H19 in human glioma cell lines and clinical tumor samples in order to determine the function of this molecule. In our research, lncRNA-H19 was specifically upregulated in glioma cell lines and promoted glioma cell growth through targeting miR-140. Knockdown of H19 inhibited the proliferation and invasion of human glioma cell and suppressed its metastasis in vitro and in vivo. In addition, miR-140 dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) regulation was required in H19 induced glioma cell growth. These findings indicated that H19 might regulate the tumor growth and metastasis via miR-140 dependent iASPP regulation. Taken together, our data indicated that H19 might be an oncogenic lncRNA that promoted proliferation and metastasis of glioma and could be regarded as a therapeutic target in human glioma.
H19是最早发现的与癌症相关的长链非编码RNA(lncRNA)之一,参与多种肿瘤的发生和发展。在肝细胞癌、宫颈癌、乳腺癌、卵巢癌和结直肠癌中均观察到H19的异常表达。然而,截至目前,H19在胶质瘤进展中的确切作用和分子机制仍不清楚。在本研究中,我们研究了H19在人胶质瘤细胞系和临床肿瘤样本中的作用,以确定该分子的功能。在我们的研究中,lncRNA-H19在胶质瘤细胞系中特异性上调,并通过靶向miR-140促进胶质瘤细胞生长。敲低H19可抑制人胶质瘤细胞的增殖和侵袭,并在体外和体内抑制其转移。此外,H19诱导的胶质瘤细胞生长需要miR-140依赖的p53凋亡刺激蛋白抑制因子(iASPP)调节。这些发现表明,H19可能通过miR-140依赖的iASPP调节来调控肿瘤生长和转移。综上所述,我们的数据表明,H19可能是一种致癌lncRNA,可促进胶质瘤的增殖和转移,并可被视为人类胶质瘤的治疗靶点。