Pa Meili, Naizaer Gulimire, Seyiti Ayinuer, Kuerbang Gulina
Department of Gynaecology, The Affiliate Tumor Hospital of Xinjiang Medical University, Urumqi City, 830011, People's Republic of China.
Oncol Res. 2017 Sep 11. doi: 10.3727/096504017X15049198963076.
Previous researches have revealed that alteration of non-coding RNAs expression level in malignancies can significantlymodify the course of diseases. Current study was aimed to investigate the biological functions of lncRNA MALAT1 and miR-200c, as well as the interaction between them. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that lncRNA MALAT1 was overexpressed in ovarian cancer tissues and cell lines in compare to adjacent normal tissue and normal human ovarian surface epithelial cells (HOSEPiCs). Contrarily, miR-200c expression was significantly decreased in ovarian cancer, which is negatively correlated with MALAT1 expression. In addition, overexpression of lncRNA MALAT1 appeared to be related to worse prognosis and higher metastasis. In consistent with clinical outcomes, down-regulation of lncRNA MALAT1 suppressed the cell viability, migration and invasion abilities of ovarian cancer cell lines. Moreover, bioinformatics analysis suggested that3'-UTR of lncRNA MALAT1 and miR-200c have a complementarity region. Rescue experiments confirmed that miR-200c could reverse the tumor-suppressive effect of knock-down of lncRNA MALAT1 on ovarian cancer cells. Nevertheless, luciferase assays verified the existence of direct binding between miR-200c and lncRNA MALAT1. In general, results of this study indicated that lncRNA MALAT1 is a oncogene in ovarian cancer, involved in the regulation of cell viability, migration and invasion abilities of ovarian cancer cells, which achieved its biological function by regulating miR-200c expression. Therefore, lncRNA MALAT1 could be a promising prognostic biomarker and therapeutic target for ovarian cancer and its relation with miR-200c might be a starting point for future researches.
以往的研究表明，恶性肿瘤中非编码RNA表达水平的改变可显著改变疾病进程。当前研究旨在探讨长链非编码RNA MALAT1和miR-200c的生物学功能及其相互作用。定量实时聚合酶链反应（qRT-PCR）显示，与相邻正常组织和正常人卵巢表面上皮细胞（HOSEPiC）相比，lncRNA MALAT1在卵巢癌组织和细胞系中过表达。相反，miR-200c在卵巢癌中的表达显著降低，且与MALAT1表达呈负相关。此外，lncRNA MALAT1的过表达似乎与较差的预后和较高的转移相关。与临床结果一致，lncRNA MALAT1的下调抑制了卵巢癌细胞系的细胞活力、迁移和侵袭能力。此外，生物信息学分析表明lncRNA MALAT1的3'-UTR与miR-200c有一个互补区域。挽救实验证实，miR-200c可逆转lncRNA MALAT1敲低对卵巢癌细胞的肿瘤抑制作用。然而，荧光素酶报告基因检测验证了miR-200c与lncRNA MALAT1之间存在直接结合。总体而言，本研究结果表明lncRNA MALAT1是卵巢癌中的一个癌基因，参与调控卵巢癌细胞的细胞活力、迁移和侵袭能力，其通过调控miR-200c的表达实现其生物学功能。因此，lncRNA MALAT1可能是一种有前景的卵巢癌预后生物标志物和治疗靶点，其与miR-200c的关系可能是未来研究的一个起点。
