Cholangiocarcinomas (CCA) is a refractory cancer with increasing incidence worldwide. Long non-coding RNAs (lncRNAs) have been shown to associate with the occurrence and development of CCA. A previous study identified upregulation of LMCD1-AS1 in CCA tissues relative to their normal counterparts by Agilent human lncRNA + mRNA arrayV4.0. However, the biological roles and molecular mechanisms of LMCD1-AS1-regulated tumorigenesis and progression of CCA remain to be elucidated. In our study, we confirmed that LMCD1-AS1 expression was significantly higher in CCA tissues and cell lines than in normal tissues and HIBEC, respectively. E2F1 could bind directly to the promoter region of LMCD1-AS1 and activate its transcription. Function study showed depletion of LMCD1-AS1 suppressed cell proliferation, clone formation and invasion, and induced apoptosis of CCA cells. Whereas, ectopic expressed LMCD1-AS1 facilitated CCA cell progression. In addition, LMCD1-AS1 could sponge miR-345-5p in CCA cells. Moreover, collagenVI-alpha3 chain (COL6A3) was found as a downstream target of miR-345-5p by bioinformatic prediction and dual luciferase reporter assay. Furthermore, we demonstrated that the oncogenic role of LMCD1-AS1 is partly dependent on COL6A3 expression. Taken together, we reported a newly identified regulatory mechanism of E2F1/LMCD1-AS1/miR-345-5p/COL6A3 axis, which might lead to a better understanding of CCA tumorigenesis and progression and provide potential therapeutic targets for CCA.
Keywords: COL6A3; Cholangiocarcinoma; E2F1; LMCD1-AS1; lncRNA; miR-345–5p.
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