CsA Promotes XIST Expression to Regulate Human Trophoblast Cells Proliferation and Invasion Through miR‐144/Titin Axis

• Published in: Journal of cellular biochemistry Vol. 118; no. 8; pp. 2208 - 2218
• Main Authors: Yu, Nanhui, Liang, Ying, Zhu, Hong, Mo, Hongying, Pei, Haiping
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2017
• Subjects: Biological activity; Blotting, Western; Cell Line, Tumor; Cell Movement - drug effects; Cell Movement - genetics; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - genetics; Connectin; Connectin - genetics; Connectin - metabolism; Correlation analysis; CsA; Cyclosporin A; Cyclosporine - pharmacology; HUMAN TROPHOBLAST CELL; Humans; MAP kinase; Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miR‐144; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Reporter gene; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; TITIN; Transcription; Trophoblasts - cytology; Trophoblasts - drug effects; Trophoblasts - metabolism; XIST; CsA; HUMAN TROPHOBLAST CELL; XIST; TITIN; miR-144
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25867

ABSTRACT In our previous study, we revealed that Cyclosporin A (CsA) could inhibit miR‐144 expression to regulate proliferation and invasion of human trophoblast (HT) cells through miR‐144 targeting titin. This partially demonstrated the mechanism by which CsA promotes titin expression to increase the vitality of HT cells. However, the mechanism by which CsA inhibits miR‐144 expression remains to be investigated. Recently, the interaction between lncRNA and miRNA has been frequently reported to play major role in several biological processes. In the present study, online tools were used to figure out that X‐inactive specific transcript (XIST) could interact with miR‐144. XIST and miR‐144 reciprocally inhibited each other in HT cells; as exhibited by luciferase reporter gene assays, miR‐144 bind to XIST by direct targeting. XIST suppressed miR‐144 expression to promote titin expression. As exhibited by the Spearman's correlation analysis, in CsA treated HT cells, miR‐144 was inversely correlated with titin and XIST, respectively; XIST was positively correlated with titin. Moreover, CsA could promote the proliferation and invasion of HT cells through XIST and the downstream MAPK and MMPs pathway. Taken together, these findings will shed light to the role and mechanism of CsA/XIST/miR‐144/titin in regulating HT cells proliferation and invasion. XIST may serve as a potential therapeutic target in HT in the future. J. Cell. Biochem. 118: 2208–2218, 2017. © 2017 Wiley Periodicals, Inc. We revealed XIST/miR‐144/titin/MAPK/MMPs link and provided a potential mechanism for CsA deregulation and contribution to HT cells proliferation and invasion. As a result, inhibition of XIST could have an important implication for the clinical management of HT cells and enhance the CsA treatment.