miR‑182‑5p contributes to radioresistance in nasopharyngeal carcinoma by regulating BNIP3 expression

Abstract

Radioresistance is the primary roadblock limiting the success of treatment of nasopharyngeal carcinoma (NPC). microRNA (miRNA/miR)-182-5p has been reported to affect the sensitivity of cancer cells to irradiation; however, the role of miR-182-5p in NPC has not been assessed. The aim of the present study was to investigate the contribution of miR-182-5p to the radioresistance of NPC cells. The key mRNA and miRNA involved in NPC radioresistance were identified using bioinformatics analysis. The two cell lines used in the present study were 5–8F cells (radio-sensitive) and 5–8F-R cells (radioresistant). A dual-luciferase reporter assay system was used to validate the binding between BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) mRNA and miR-182-5p. Reverse transcription-quantitative PCR and western blotting were used to determine the RNA and protein expression levels. To obtain a deeper insight into the effects of the BNIP3/miR-182-5p axis on NPC radioresistance, Cell Counting Kit-8, wound healing, Transwell invasion and colony formation assays, as well as flow cytometry analysis were performed. The results showed that miR-182-5p and BNIP3 were up and downregulated, respectively, in 5–8F-R cells. BNIP3 was also confirmed to be the target of miR-182-5p, and miR-182-5p reversed the inhibitory effect of BNIP3 in 5–8F-R cells. The cellular experiments showed that upregulation of BNIP3 not only inhibited cell proliferation, viability, invasion and migration, but also promoted the apoptosis of 5–8F-R cells. However, the effects of BNIP3 were attenuated by the simultaneous upregulation of miR-182-5p. Thus, through downregulation of BNIP3, miR-182-5p contributed to radiation resistance of NPC cells.

Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum

“…The neuroprotective effect of miR-182 in mice following SCI was a consequence of the suppression of apoptosis in neurons [48]. It was also shown that the inhibition of miR-182-5p increased the sensitivity to irradiation in nasopharyngeal carcinoma cells, suggesting that miR-182-5p contributes to cellular radioresistance [49]. Accordingly, miR-182 was upregulated in lung cancer, and its inhibition sensitized cancer cells to ionizing radiation by suppressing cell proliferation and increasing cell apoptosis after irradiation, suggesting that miR-182 might account for radioresistance in lung cancer [50].…”

Bioinformatics analysis of differentially expressed genes in diabetic foot ulcer and preliminary experimental verification

“…Also, silent mating-type information regulator 2 homolog 1 ( SIRT1 ) is significantly down-regulated in DF patients, and the C allele of rs12778366 polymorphism of the SIRT1 gene may be a protective factor for DF ( 9 ). Moreover, the overexpression of taurine-upregulated genes 1 ( TUG1 ) can restore endothelial progenitor cells (EPC) function after HG treatment by regulating the miR-29c-3p /PDGF-BB/Wnt signaling pathway ( 10 ). The upregulation of active-matrix metalloproteinase (MMP-9) results in diabetic wound healing difficulties in mice, and the inhibitor of MMP-9 is expected to be an effective treatment ( 11 ).…”

“…In previous studies, it was observed that some genes were differentially expressed in DFU and control groups, which played different roles in the occurrence and development of diseases through different mechanisms of action (8)(9)(10)(11)(12)(13). For example, rs1024611 polymorphism of the monocyte chemoattractant protein-1 (MCP-1) gene is significantly correlated with MCP-1 expression and individual susceptibility to DFU (8).…”

Cross‑link between ferroptosis and nasopharyngeal carcinoma: New approach to radiotherapy sensitization (Review)

“…To date, several studies have demonstrated that miRNAs regulating ferroptosis are associated with the proliferation, invasion, migration and apoptosis of NPC cells, particularly in terms of radiosensitivity regulation ( Table I ). For instance, miR-214 and miR-182-5p were indicated to contribute to radioresistance in NPC by regulating LTF and BNIP3 expression ( 103 , 104 ). However, miR-124 and miR-9 may promote radiosensitivity of NPC via targeting programmed cell death protein 6 (PDCD6) and suppressing the expression of junctional adhesion molecule A (JAMA) ( 105 – 107 ).…”