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Long noncoding RNA CRNDE functions as a competing endogenous RNA to promote metastasis and oxaliplatin resistance by sponging miR-136 in colorectal cancer

Authors Gao H, Song X, Kang T, Yan B, Feng L, Gao L, Ai L, Liu X, Yu J, Li H

Received 1 July 2016

Accepted for publication 20 September 2016

Published 5 January 2017 Volume 2017:10 Pages 205—216

DOI https://doi.org/10.2147/OTT.S116178

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Professor Min Li

Hongyan Gao,1 Xiaodi Song,2 Ting Kang,3 Baohong Yan,4 Li Feng,5 Li Gao,6 Liang Ai,6 Xiaoni Liu,7,* Jie Yu,8,* Huiqi Li9,*

1Department of Gastroenterology, The First Affiliated Hospital of Xi’an Medical University, 2Department of Pharmacy, Xi’an Central Hospital, Xi’an, 3Department of Oncology, Yan’an University Affiliated Hospital, Yan’an, 4Department of Pharmacy, Hong-Hui Hospital, Xi’an Jiaotong University Medical College, Xi’an, 5Department of Anorectal Surgery, Ankang City Central Hospital, Ankang, 6Department of Pharmacy, Yan’an University Affiliated Hospital, 7Department of Endocrinology, Yan’an People’s Hospital, Yan’an, 8Department of General Surgery, Nuclear Industry 215 Hospital of Shaanxi Province, Xianyang, 9Department of General Surgery, The People’s Hospital of Baoji City, Baoji, People’s Republic of China

*These authors contributed equally to this work

Abstract: Colorectal neoplasia differentially expressed (CRNDE) is a novel gene recognized as a long noncoding RNA (lncRNA) that is highly elevated in colorectal cancer and many other solid tumors but its functions on metastasis and oxaliplatin (OXA) resistance are unknown. In our study, we confirmed the upregulation of CRNDE in both primary specimens from colorectal cancer patients and colorectal cancer cell lines. Knockdown of CRNDE expression inhibited the migration and invasion potency of colorectal cancer cells with no effect on cell apoptosis. Overexpression of CRNDE promoted the migration and invasion potency of colorectal cancer cells. Furthermore, we found that CRNDE conferred chemoresistance in colorectal cancer cells. Knockdown of CRNDE with OXA treatment decreased cell viability and promoted DNA damage and cell apoptosis, while the overexpression of CRNDE with OXA treatment reduced DNA damage and cell apoptosis. Further in-depth mechanistic studies revealed that CRNDE functioned as a competing endogenous RNA for miR-136, led to the de-repression of its endogenous target, E2F transcription factor 1 (E2F1). Overall, our findings demonstrate that CRNDE functions as a competing endogenous RNA to promote metastasis and OXA resistance by sponging miR-136 in colorectal cancer.

Keywords: CRNDE, colorectal cancer, metastasis, oxaliplatin resistance, miR-136, E2F1

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