MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing

Abstract

Betel nut chewing is associated with oral cavity cancer. Radiotherapy is one of the therapeutic approaches. Here, we used miR-17-5p antisense oligonucleotides (AS-ODNs) and human apoptosis protein array to clarify which apoptosis-related proteins are increased or decreased by miR-17-5p in betel nut chewing- oral squamous cell carcinoma OC3 cells. Furthermore, miR-17-5p AS-ODN was used to evaluate the radio-sensitization effects both in vitro and in vivo. An OC3 xenograft tumor model in severe combined immunodeficiency mice was used to determine the effect of miR-17-5p AS ODN on tumor irradiation. We simultaneously detected the relative expressions of 35 apoptosis-related proteins in irradiated OC3 cells that were treated with miR-17-5p AS-ODN or a control ODN. Several proteins, including p21, p53, TNF RI, FADD, cIAP-1, HIF-1α, and TRAIL R1, were found to be up- or downregulated by miR-17-5p in OC3 cells; their expression patterns were also confirmed by Western blotting. We further clarified the role of p53 in irradiated OC3 cells, using a p53 overexpression strategy. The results revealed that the enhancement of p53 expression significantly enhanced radiation-induced G2/M arrest of the OC3 cells. In the in vivo study, treatment of miR-17-5p AS-ODN before irradiation significantly enhanced p53 expression and reduced tumor growth. These results suggest that miR-17-5p increases or decreases apoptosis-related proteins in irradiated OC3 cells; its effect on p53 protein expression contributes to the modulation of the radiosensitivity of the OC3 cells.

Exosomal miRNA-17-5p derived from human umbilical cord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7

“…30 miR-17-5P has also been reported to promote proliferation and suppress apoptosis. [31][32][33] Other miRNAs, including miR-125b-5p, miR-21, and miR-146a, have been found to be enriched in MSC-Exos, regulating inflammation, promoting proliferation and showing curative effects. 34,35 F I G U R E 6 Exosomal miRNA-17-5P repressed ROS accumulation by regulating SIRT7 in a CTX-induced POI mouse model.…”

Biomarker MicroRNAs for Diagnosis of Oral Squamous Cell Carcinoma Identified Based on Gene Expression Data and MicroRNA-mRNA Network Analysis

“…MicroRNA-27a-3p can regulate transition from epithelial to mesenchymal in OSCC by targeting YAP1 [ 13 ]. The apoptosis-related protein expression and radiosensitivity in BQ-associated OSCC are regulated by microRNA-17-5p [ 14 ]. Metabolic shift in OSCC is mediated by microRNA-340 targeting glucose transporter-1 [ 15 ].…”

Prognostic value of miR-17-5 p in gastrointestinal cancers: a systematic review and meta-analysis

“… 41 By performing a similar study in radiotherapy, Wu et al identified that miRNA-17-5 p regulated radiosensitivity in oral squamous cell carcinoma. 42 The downregulated mir-17-5 p in esophageal adenocarcinoma cancer stem-like cells may promote the radioresistant phenotype. 43 …”