Downregulation of miR-423-5p Contributes to the Radioresistance in Colorectal Cancer Cells

Abstract

Resistance to radiotherapy is the main reason causing treatment failure in locally advanced rectal cancer. MicroRNAs (miRNAs) have been well demonstrated to regulate cancer development and progression. However, how miRNAs regulate radiotherapy resistance in colorectal cancer remains unknown. Herein, we established two human colorectal cancer cell lines resistant to radiotherapy, named HCT116-R and RKO-R, using the strategy of fractionated irradiation. The radioresistant phenotypical changes of the two cell lines were validated by cell viability assay, colony formation assay and apoptosis assay. The miRNA expression profilings of HCT116-R and RKO-R were determined using RNA-seq analyses, and further confirmed by quantitative real-time PCR. Multiple miRNAs, including miR-423-5p, miR-7-5p, miR-522-3p, miR-3184-3p, and miR-3529-3p, were identified with altered expression in both of the radiotherapy-resistant cells, compared to the parental cells. The downregulation of miR-423-5p was further validated in the rectal cancer tissues from radiotherapy-resistant patients. Silencing of miR-423-5p in parental HCT116 and RKO cells decreased the sensitivity to radiation treatment, and inhibited the radiation-induced apoptosis. In consistence, overexpression of miR-423-5p in HCT116-R and RKO-R cells partially rescued their sensitivity to radiotherapy, and promoted the radiation-induced apoptosis. Bcl-xL (Bcl-2-like protein 1) was predicted to be a potential target gene for miR-423-5p, and miR-423-5p/Bcl-xL axis could be a critical mediator of radiosensitivity in colorectal cancer cells. The current finding not only revealed a novel role of miR-423-5p in regulating the radiosensitivity in colorectal cancer, but also suggested miR-423-5p as a molecular candidate for combination therapy with radiation to treat colorectal cancer.

LIMK2 Is a Novel Prognostic Biomarker and Correlates With Tumor Immune Cell Infiltration in Lung Squamous Cell Carcinoma

“…In this study, we tried to determine the upstream miRNAs of LIMK2 based on the ceRNA hypothesis; with the help of the miMAP, miRDB, StarBASE, and TargetScan databases, we found that miR-423-5p is likely to be the upstream regulatory miRNA of the LIMK2 gene in LUSC. Studies have demonstrated that miR-423-5p is associated with tumor development and poor prognosis of patients (43)(44)(45)(46)(47). Then, upstream regulatory lncRNAs of miR-423-5p/LIMK2 were predicted by the StarBASE and lncBASE databases.…”

Integrated microRNA–mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Autism

“…Several miRNAs involved in cancer show dysregulated expression in ASD LCLs, including miR-6732-3p , hsa-miR-221-5p [ 64 , 65 ], hsa-miR-21-5p [ 66 , 67 ], hsa-miR-152-3p [ 68 , 69 ], hsa-miR-3529-3p [ 70 , 71 ], and has-miR-148b-3p [ 72 , 73 ]. Additionally, miR-3529-3p was 2-fold upregulated in ASD LCLs and it targets GABRA4 ( Table S7 ) and this miRNA promotes angiogenesis [ 71 ].…”

“…Additionally, miR-3529-3p was 2-fold upregulated in ASD LCLs and it targets GABRA4 ( Table S7 ) and this miRNA promotes angiogenesis [ 71 ]. Studies have shown miR-3529-3p to be upregulated in radiotherapy-resistant colorectal cancer cells [ 70 ] and downregulated in liver cancer [ 74 ].…”

MicroRNAs Targeting HIF-2α, VEGFR1 and/or VEGFR2 as Potential Predictive Biomarkers for VEGFR Tyrosine Kinase and HIF-2α Inhibitors in Metastatic Clear-Cell Renal Cell Carcinoma

“…miR-3529-3p overexpression also negatively impacts OS. miR-3529-3p is upregulated in radiotherapy-resistant colorectal cancer cells [ 76 ]. To our best knowledge, this is the first study to demonstrate an association between miR-3529-3p and angiogenesis.…”