E2F1-induced upregulation of long non-coding RNA LMCD1-AS1 facilitates cholangiocarcinoma cell progression by regulating miR-345–5p/COL6A3 pathway

• Published in: Biochemical and biophysical research communications 2019-04, Vol.512 (2), p.150-155
• Main Authors: Yu, Jing, Zhang, Bingquan, Zhang, Han, Qi, Yi, Wang, Yanying, Wang, Wenbin, Wang, Yang, Wang, Yan
• Format: Article
• Language: English
• Subjects: Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - metabolism; Bile Duct Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation; Cholangiocarcinoma; Cholangiocarcinoma - genetics; Cholangiocarcinoma - metabolism; Cholangiocarcinoma - pathology; COL6A3; Collagen Type VI - genetics; Disease Progression; E2F1; E2F1 Transcription Factor - metabolism; Gene Expression Regulation, Neoplastic; Humans; LMCD1-AS1; lncRNA; MicroRNAs - genetics; miR-345–5p; RNA, Long Noncoding - genetics; Up-Regulation
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.03.054

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. •LncRNA LMCD1-AS1 is upregulated in CCA tissues and cell lines.•E2F1 could bind directly to the promoter region of LMCD1-AS1 and activate its transcription.•LMCD1-AS1 functions as an oncogene in CCA cells.•LMCD1-AS1 sponges miR-345–5p to regulate COL6A3 expression at post-transcriptional level.•E2F1/LMCD1-AS1/miR-345–5p/COL6A3 axis was essential for tumorigenesis and progression of CCA.