The lncRNA XIST interacts with miR-140/miR-124/iASPP axis to promote pancreatic carcinoma growth
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Shuai Liang1, Xuejun Gong1, Gewen Zhang1, Gengwen Huang1, Yebin Lu1 and Yixiong Li1
1Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, China
Yixiong Li, email: firstname.lastname@example.org
Keywords: XIST; pancreatic carcinoma (PC); cell cycle; miR-140/miR-124; iASPP
Received: May 04, 2017 Accepted: June 20, 2017 Published: November 20, 2017
Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the development and progression of many tumors. In this study, XIST was specifically upregulated in pancreatic carcinoma tissues and cell lines; a higher XIST expression was correlated to poorer clinicopathologic features. After XIST knockdown, the proliferation of PC cell lines was suppressed and cell cycle stagnated in G1 phase; XIST knockdown also reduced the protein levels of inhibitor of apoptosis-stimulating protein of p53 (iASPP) and Cyclin-dependent kinase 1 (CDK1), increased the protein level of P21, a potent CDK inhibitor. In PC cell lines, XIST and miR-140/miR-124, two tumor-associated miRNAs, could inversely regulate each other, respectively; miR-140/miR-124 could bind to XIST and the 3’UTR of PPP1R13L, respectively. XIST and miR-140/miR-124 exerted opposite effects on iASPP, CDK1, P21 and P27 proteins; whereas the effects of LV-sh-XIST on the indicated protein levels could be partially reversed by miR-140 and/or miR-124 inhibitor. In PC tissues, miR-140 and miR-124 expression was down-regulated, iASPP and CDK1 mRNA expression was up-regulated. XIST positively correlated with iASPP and CDK1, inversely correlated with miR-140 and miR-124, respectively. Taken together, our data indicated that XIST might be an oncogenic lncRNA that promoted proliferation of PC cell line through inhibiting miR-140/miR-124 expression and promoting cell cycle-related factor expression, and could be regarded as a therapeutic target in human pancreatic carcinoma.
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