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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2019

Open Access 01-12-2019 | Pancreatic Cancer | Research

Long non-coding RNA LINC00346 promotes pancreatic cancer growth and gemcitabine resistance by sponging miR-188-3p to derepress BRD4 expression

Authors: Weidong Shi, Chenyue Zhang, Zhouyu Ning, Yongqiang Hua, Ye Li, Lianyu Chen, Luming Liu, Zhen Chen, Zhiqiang Meng

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2019

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Abstract

Background

Long non-coding RNA LINC00346 has been recently suggested as a prognostic marker in pancreatic cancer. However, its biological function in pancreatic cancer has not yet been determined. In this study, we attempted to ascertain the role of LINC00346 in regulating the aggressiveness of pancreatic cancer.

Methods

The effects of overexpression and knockdown of LINC00346 on the proliferation, cell cycle progression, apoptosis, and gemcitabine resistance were investigated. Bioinformatic analysis, luciferase reporter assay, and RNA immunoprecipitation assay were performed to search for potential microRNAs (miRs) that can interact with LINC00346.

Results

Overexpression of LINC00346 significantly enhanced the proliferation, colony formation, and tumorigenesis of pancreatic cancer cells. Conversely, knockdown of LINC00346 suppressed pancreatic cancer cell proliferation and caused a cell-cycle arrest at the G2/M-phase. Depletion of LINC00346 also enhanced gemcitabine sensitivity in pancreatic cancer cells both in vitro and in vivo. Mechanistic investigation revealed that LINC00346 acted as a sponge for miR-188-3p and blocked the repression of BRD4 by miR-188-3p in pancreatic cancer cells. Clinical evidence indicated a negative correlation between LINC00346 and miR-188-3p in pancreatic cancer specimens. Rescue experiments showed that LINC00346 attenuated the growth-suppressing and chemosensitizing effects of miR-188-3p on pancreatic cancer cells. In addition, silencing of BRD4 significantly inhibited LINC00346-induced pancreatic cancer cell proliferation and colony formation.

Conclusions

LINC00346 shows the ability to promote pancreatic cancer growth and gemcitabine resistance, which is in part mediated by antagonization of miR-188-3p and induction of BRD4. Targeting LINC00346 may improve gemcitabine-based therapeutic efficacy.
Appendix
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Metadata
Title
Long non-coding RNA LINC00346 promotes pancreatic cancer growth and gemcitabine resistance by sponging miR-188-3p to derepress BRD4 expression
Authors
Weidong Shi
Chenyue Zhang
Zhouyu Ning
Yongqiang Hua
Ye Li
Lianyu Chen
Luming Liu
Zhen Chen
Zhiqiang Meng
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2019
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-019-1055-9

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