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Up-regulated LncRNA-ATB regulates the growth and metastasis of cholangiocarcinoma via miR-200c signals.

Research paper by Hai H Lin, Lili L Yang, Feng F Tian, Shuang S Nie, Hailang H Zhou, Jun J Liu, Weichang W Chen

Indexed on: 03 Oct '19Published on: 02 Oct '19Published in: OncoTargets and therapy



Abstract

Cholangiocarcinoma (CCA) is a highly aggressive neoplasm featured with regional invasiveness and distant metastasis, which often present a phenotype of epithelial-mesenchymal transition (EMT). Long non-coding RNAs (LncRNAs) are dysregulated during carcinogenesis, and up-regulated LncRNA-activated by TGF-β (Lnc-ATB) supports tumor growth and metastasis via tumor suppressor microRNA 200 (miR-200). However, the role of Lnc-ATB in CCA is unclear. CCA tissues and non-cancer tissues (n=30) were used to determine the Lnc-ATB and miR-200a/b/c levels. The functions and mechanisms of Lnc-ATB/miR-200 pathway were determined by knockdown of Lnc-ATB via siRNAs in vitro and in vivo. CCA tissues have increased Lnc-ATB and reduced miR-200a/b/c levels, but the down-regulated miR-200c was most prominent. Up-regulated Lnc-ATB significant negatively correlated with miR-200c and predicted advanced TNM stage and more lymph node metastasis of CCA patients. Knockdown of Lnc-ATB in two CCA cell lines HuCCT1 and RBE increased miR-200c levels. The luciferase reporter assay further confirmed the direct binding site of miR-200c in Lnc-ATB. Inhibition of Lnc-ATB significantly impaired cell vitality and induced apoptosis and G0/G1 arrest, which, however, was rescued by miR-200c inhibitor. The ability of migration of CCA cells was also up-regulated by Lnc-ATB but was suppressed by miR-200c. Mechanistically, the cell cycle-related CCND1/CDK2, apoptosis-related BCL-2/caspase-3 and EMT-related E-cadherin/ZEB1/2 were regulated by Lnc-ATB via miR-200c. Knockdown of Lnc-ATB in vivo up-regulated miR-200c signals to inhibit tumor growth with decreased PCNA expression in tumor tissues, which was restored by miR-200c inhibition. Overexpressed Lnc-ATB functioned as an oncogene for CCA growth and metastasis via miR-200 signals. © 2019 Lin et al.