Downregulation of MiR-874-3p Promotes Chemotherapeutic Resistance in Colorectal Cancer Via Inactivation of the Hippo Signaling Pathway

Overview

Journal Oncol Rep

Specialty Oncology

Date 2017 Oct 18

PMID 29039607

Citations 20

Authors

Kaiqian Que

Yuanhe Tong

Ganbo Que

Li Li

Hongcheng Lin

Shuai Huang

Ruoyu Wang

Langlang Tang

Affiliations

Soon will be listed here.

Abstract

Overcoming resistance to chemotherapy is an arduous challenge in the treatment of colorectal cancer (CRC), particularly since the underlying molecular mechanisms remain obscure. In the present study, we reported that miR‑874-3p was markedly downregulated in CRC tissues compared with that in adjacent normal colorectal epithelial tissues. Upregulation of miR-874-3p attenuated the chemoresistance of CRC cells to 5-fluorouracil (5-FU) in vitro and in vivo. Conversely, inhibition of miR-874-3p yielded an opposite effect. Furthermore, our results demonstrated that miR-874-3p directly inhibited the expression of transcriptional co-activators YAP and TAZ of the Hippo signaling pathway, resulting in the inactivation of the TEAD transcription. Thus, our findings clarify a novel mechanism by which miR-874-3p restores chemotherapeutic sensitivity of CRC to 5-FU, indicating that offering miR-874-3p mimics in combination with 5-FU may serve as a new therapeutic strategy to circumvent the chemoresistance in CRC.

Citing Articles

Hippo Signaling Pathway in Colorectal Cancer: Modulation by Various Signals and Therapeutic Potential.

Mohammadpour S, Torshizi Esfahani A, Sarpash S, Vakili F, Zafarjafarzadeh N, Mashaollahi A Anal Cell Pathol (Amst). 2024; 2024:5767535.

PMID: 39431199 PMC: 11489006. DOI: 10.1155/2024/5767535.

Targeting Hippo signaling in cancer: novel perspectives and therapeutic potential.

Lv L, Zhou X MedComm (2020). 2023; 4(5):e375.

PMID: 37799806 PMC: 10547939. DOI: 10.1002/mco2.375.

Shikonin impedes type 2 ovarian cancer progression via FasL/caspase-8 and mir-874-3p/XIAP axis and prohibits the properties of stemness.

Chang Y, Lin Y, Huang C, Harnod T, Ding D Am J Cancer Res. 2022; 12(10):4584-4601.

PMID: 36381333 PMC: 9641410.

Knockdown of circ_0004585 enhances the chemosensitivity of colorectal cancer cells to 5-fluorouracil via the miR-874-3p/CCND1 axis.

Wang S, Cao J, Pei L Histol Histopathol. 2022; 38(1):99-112.

PMID: 35900059 DOI: 10.14670/HH-18-502.

Generation of TRIM28 Knockout K562 Cells by CRISPR/Cas9 Genome Editing and Characterization of TRIM28-Regulated Gene Expression in Cell Proliferation and Hemoglobin Beta Subunits.

Chang Y, Kang Z, Bei J, Chou S, Lu M, Su Y Int J Mol Sci. 2022; 23(12).

PMID: 35743282 PMC: 9224613. DOI: 10.3390/ijms23126839.

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