LncRNA‐MEG3 inhibits cell proliferation and invasion by modulating Bmi1/RNF2 in cholangiocarcinoma. Issue 12 (22nd May 2019)

• Record Type: Journal Article
• Authors: Li, Jinglin; Jiang, Xingming; Li, Chunlong; Liu, Yueping; Kang, Pengcheng; Zhong, Xiangyu; Cui, Yunfu
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 12(2019:Dec.)
• Page Start: 22947
• Page End: 22959
• Publication Date: 2019-05-22
• Subjects: cholangiocarcinoma -- lncRNA -- MEG3 -- tumor suppressor; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28856
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Cholangiocarcinoma (CCA) is a mortal cancer with gradually increasing incidences all over the world, whereas effective diagnosis and treatment for this disease are still lacking. As a classical long noncoding RNA (lncRNA), maternally expressed gene 3 (MEG3) has been reported to exhibit pivotal regulatory roles in the occurrence and development of various digestive system tumors. Nevertheless, the clinical relevance and biological function of MEG3 in CCA remain largely unclear. In this study, MEG3 expression was significantly downregulated in both CCA tissues and cells in comparison with that in nontumor controls, respectively, and this downexpression was prominently associated with advanced TNM stage, lymph node invasion, and poor survival. Moreover, decreased MEG3 was an independent forecaster of poor prognosis for CCA patients. Functionally, MEG3 overexpression inhibited CCA growth in vitro and in vivo. Enhanced MEG3 also suppressed migration and invasion of CCLP‐1 and QBC939 cells by reversing epithelial‐mesenchymal transition (EMT) process. On the contrary, the proliferation, metastasis, and EMT were facilitated via knocking down MEG3. In addition, the expression of B lymphoma Mo‐MLV insertion region 1 (Bmi1) and RING finger protein 2 was impacted by gain or loss of MEG3, furthermore, the malignant processes induced by MEG3 knockdown were rescued by means of silencing Bmi1. These data suggested that MEG3 caused tumor suppressive effects partly through mediating polycomb repressive complex 1. Our findings elucidate that MEG3 exerts critical functions in CCA development and likely acts as a promising tumor indicator or intervention target for CCA. Abstract : Long noncoding RNA‐MEG3 can inhibit proliferation, migration, and invasion as well as epithelial‐mesenchymal transition process of cholangiocarcinoma (CCA) cells by regulating Bmi1/RNF2 complex, and downregulated maternally expressed gene 3 represents a poor prognosis of CCA patients. This RNA is expected to be a potential biomarker or therapeutic target for suppressing CCA progression clinically.