Nie Feng-Qi, Zhu Quan, Xu Tong-Peng, Zou Yan-Fen, Xie Min, Sun Ming, Xia Rui, Lu Kai-Hua
Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Tumour Biol. 2014 Aug;35(8):7587-94. doi: 10.1007/s13277-014-2009-7. Epub 2014 May 4.
Long non-coding RNAs (lncRNAs) have emerged as major players in governing fundamental biological processes, and many of which are misregulated in multiple cancers and likely to play a functional role in tumorigenesis. Therefore, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. lncRNA associated with microvascular invasion in HCC (lncRNA MVIH) was found to be generally upregulated in HCC. Moreover, MVIH overexpression could serve as an independent risk factor to predict poor RFS and promote tumor growth and metastasis via activating angiogenesis. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression is unknown. In this study, we found that lncRNA MVIH levels were increased in NSCLC tissues compared with adjacent normal tissues. Its expression level was significantly correlated with TNM stages, tumor size, and lymph node metastasis. Moreover, patients with high levels of MVIH expression had a relatively poor prognosis. Furthermore, knockdown of MVIH expression by siRNA could inhibit cell proliferation and invasion, while ectopic expression of MVIH promoted cell proliferation and invasion in NSCLC cells partly via regulating MMP2 and MMP9 protein expression. Our findings present that increased lncRNA MVIH could be identified as a poor prognostic biomarker in NSCLC and regulate cell proliferation and invasion.
长链非编码RNA(lncRNAs)已成为调控基本生物学过程的主要参与者,其中许多在多种癌症中表达失调,并可能在肿瘤发生中发挥功能作用。因此,鉴定与癌症相关的lncRNAs并研究其生物学功能和分子机制对于理解癌症的发生和发展至关重要。在肝癌中与微血管侵犯相关的lncRNA(lncRNA MVIH)被发现通常在肝癌中上调。此外,MVIH的过表达可作为预测无复发生存期差的独立危险因素,并通过激活血管生成促进肿瘤生长和转移。然而,其在非小细胞肺癌(NSCLC)发生和发展中的生物学作用和临床意义尚不清楚。在本研究中,我们发现与相邻正常组织相比,NSCLC组织中lncRNA MVIH水平升高。其表达水平与TNM分期、肿瘤大小和淋巴结转移显著相关。此外,MVIH表达水平高的患者预后相对较差。此外,通过siRNA敲低MVIH表达可抑制细胞增殖和侵袭,而MVIH的异位表达部分通过调节MMP2和MMP9蛋白表达促进NSCLC细胞的增殖和侵袭。我们的研究结果表明,lncRNA MVIH的增加可被鉴定为NSCLC中不良预后的生物标志物,并调节细胞增殖和侵袭。