Department of Respiratory Medicine, Xiangya Hospital, Central South University; Key Institute of National Clinical Research Center for Respiratory Disease of China, Changsha, Hunan 410008, P.R. China.
Oncol Rep. 2017 Aug;38(2):941-948. doi: 10.3892/or.2017.5751. Epub 2017 Jun 26.
X-inactive specific transcript (XIST), one of the first found cancer-associated long non-coding RNAs (lncRNAs), is involved in the development and progression of many types of tumors. Aberrant expression of XIST has been observed in hepatocellular carcinoma, cervical, breast, ovarian and colorectal cancer. However, the exact effects and molecular mechanisms of XIST in lung cancer progression are still unknown to date. In the present study, we investigated the role of XIST in human lung cancer cell lines and clinical tumor samples in order to determine the function of this molecule. In our research, lncRNA-XIST was specifically upregulated in lung cancer cell lines and promoted lung cancer cell growth through targeting miR-140. Knockdown of XIST inhibited the proliferation and promoted cell apoptosis of human lung cancer cells and suppressed metastasis in vitro and in vivo. In addition, miR-140-dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) regulation was required in XIST-induced lung cancer cell growth. These findings indicated that XIST may regulate the tumor growth and metastasis via miR-140-dependent iASPP regulation. Taken together, our data indicated that XIST may be an oncogenic lncRNA that promotes the proliferation and metastasis of lung cancer through the regulation of miR-140 and could be regarded as a therapeutic target in human lung cancer.
X 失活特异性转录物（XIST）是最早发现的与癌症相关的长非编码 RNA（lncRNA）之一，参与多种类型肿瘤的发生和发展。XIST 的异常表达已在肝癌、宫颈癌、乳腺癌、卵巢癌和结直肠癌中观察到。然而，XIST 在肺癌进展中的确切作用和分子机制迄今尚不清楚。在本研究中，我们研究了 XIST 在人肺癌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-XIST 在肺癌细胞系中特异性地上调，并通过靶向 miR-140 促进肺癌细胞生长。XIST 的敲低抑制了人肺癌细胞的增殖并促进了细胞凋亡，并抑制了体外和体内的转移。此外，XIST 诱导的肺癌细胞生长需要依赖 miR-140 的凋亡刺激蛋白 p53 抑制剂凋亡刺激蛋白（iASPP）的调节。这些发现表明，XIST 可能通过 miR-140 依赖性 iASPP 调节来调节肿瘤的生长和转移。总之，我们的数据表明，XIST 可能是一种致癌 lncRNA，通过调节 miR-140 促进肺癌的增殖和转移，并可作为人类肺癌的治疗靶点。
