Microrna-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing
Journal
Oncotarget
Journal Volume
7
Journal Issue
32
Pages
51482-51493
Date Issued
2016
Author(s)
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 (ASODNs) 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 radiosensitization 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-1a, 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.
Subjects
Apoptosis; miR-17-5p; OC3 cells; P53; Radiation
SDGs
Other Subjects
antisense oligonucleotide; cellular inhibitor of apoptosis 1; death receptor 4; Fas associated death domain protein; hypoxia inducible factor 1alpha; inhibitor of apoptosis protein; microRNA; microRNA 17 5p; protein p21; protein p53; tumor necrosis factor receptor 1; unclassified drug; apoptosis regulatory protein; microRNA; MIRN17 microRNA, human; aged; animal cell; animal experiment; animal model; animal tissue; Article; betel nut; cancer inhibition; cancer radiotherapy; controlled study; down regulation; G2 phase cell cycle checkpoint; gene overexpression; human; human apoptosis protein array; human cell; in vitro study; in vivo study; male; mouse; mouth squamous cell carcinoma; nonhuman; OC3 cell line; protein expression; protein microarray; radiosensitivity; SCID mouse; squamous cell carcinoma cell line; tumor model; tumor xenograft; upregulation; Western blotting; animal; apoptosis; Areca; chemically induced; gene expression regulation; genetics; mastication; mouth tumor; pathology; physiology; radiation tolerance; squamous cell carcinoma; toxicity; tumor cell line; Animals; Apoptosis; Apoptosis Regulatory Proteins; Areca; Carcinoma, Squamous Cell; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Male; Mastication; Mice; Mice, SCID; MicroRNAs; Mouth Neoplasms; Radiation Tolerance
Publisher
Impact Journals LLC
Type
journal article