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LncRNA NEAT1 Regulates 5-Fu Sensitivity, Apoptosis and Invasion in Colorectal Cancer Through the MiR-150-5p/CPSF4 Axis

Authors Wang X, Jiang G, Ren W, Wang B, Yang C, Li M

Received 20 November 2019

Accepted for publication 4 June 2020

Published 1 July 2020 Volume 2020:13 Pages 6373—6383


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Takuya Aoki

Xuesong Wang, Guosheng Jiang, Weidan Ren, Bo Wang, Chuanwei Yang, Meishuang Li

Department of Colorectal & Anal Surgery, Central Hospital of Cangzhou, Cangzhou 061000, Hebei, People’s Republic of China

Correspondence: Xuesong Wang Tel +86-18031792097

Background: Colorectal cancer (CRC) is one of the most prevalent malignancies in the world. Long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) is involved in the development of many cancers. However, its role and mechanism in CRC progression still need further exploration.
Methods: The expression levels of lnc-NEAT1, microRNA-150-5p (miR-150-5p) and cleavage and polyadenylation specific factor 4 (CPSF4) were determined by quantitative real-time PCR (qRT-PCR). The sensitivity of cells to 5-fluorouracil (5-Fu) was measured by 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis and invasion were evaluated by flow cytometry and transwell assays, respectively. Western blot (WB) analysis was used to assess the levels of resistance-related proteins and CPSF4 protein. Besides, dual-luciferase reporter assay was used to verify the interactions among lnc-NEAT1, miR-150-5p and CPSF4. Also, mice xenograft models were used to determine the effect of lnc-NEAT1 on CRC tumor growth in vivo.
Results: In CRC, the expression of lnc-NEAT1 was upregulated and miR-150-5p was downregulated, and the expression of both was negatively correlated. Silencing of lnc-NEAT1 promoted the 5-Fu sensitivity, enhanced the apoptosis and suppressed the invasion of CRC cells. MiR-150-5p could be sponged by lnc-NEAT1, and its inhibitors could partially reverse the effect of lnc-NEAT1 silencing on CRC progression. Besides, CPSF4 could be targeted by miR-150-5p, and its overexpression also could invert the effect of lnc-NEAT1 knockdown on CRC progression. Further, CPSF4 expression was regulated by lnc-NEAT1 and miR-150-5p. In addition, interference of lnc-NEAT1 reduced tumor volume and improved the sensitivity of CRC to 5-Fu in vivo.
Conclusion: Lnc-NEAT1 acted as an oncogene in CRC through regulating CPSF4 expression by sponging miR-150-5p. The discovery of lnc-NEAT1/miR-150-5p/CPSF4 axis provided a novel approach for CRC genomic therapy strategy.

Keywords: CRC, lnc-NEAT1, CPSF4, miR-150-5p

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