1. Downregulation of miR-874-3p promotes chemotherapeutic resistance in colorectal cancer via inactivation of the Hippo signaling pathway
- Author
-
Langlang Tang, Hongcheng Lin, Kaiqian Que, Ganbo Que, Shuai Huang, Li Li, Yuanhe Tong, and Ruoyu Wang
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Colorectal cancer ,Cell ,colorectal cancer ,Apoptosis ,Protein Serine-Threonine Kinases ,Biology ,miR-874-3p ,03 medical and health sciences ,Downregulation and upregulation ,medicine ,chemotherapeutic resistance ,Humans ,Hippo Signaling Pathway ,Aged ,Cell Proliferation ,Regulation of gene expression ,Hippo signaling pathway ,Oncogene ,Nuclear Proteins ,TEA Domain Transcription Factors ,Articles ,General Medicine ,Middle Aged ,Cell cycle ,medicine.disease ,Xenograft Model Antitumor Assays ,Molecular medicine ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Drug Resistance, Neoplasm ,Cancer research ,Female ,Fluorouracil ,Colorectal Neoplasms ,Signal Transduction ,Transcription Factors - 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.
- Published
- 2017
- Full Text
- View/download PDF