BackgroundGlioma is the most prevalent malignant tumor in human central nervous systems. Recently, the development of resistance to radiotherapy in glioma patients markedly vitiates the therapy outcome. MiR-153-3p has been reported to be closely correlated with tumor progression, but its effect and molecular mechanism underlying radioresistance remains unclear in glioma.MethodsThe expression of miR-153-3p was determined in radioresistant glioma clinical specimens as well as glioma cell lines exposed to irradiation (IR) using quantitative real-time PCR. Cell viability, proliferation and apoptosis were then evaluated by MTT assay, colony formation assay, Flow cytometry analysis and caspase-3 activity assay in glioma cells (U87 and U251). Tumor forming was evaluated by nude mice model in vivo. TUNEL staining was used to detect cell apoptosis in nude mice model. The target genes of miR-153-3p were predicted and validated using integrated bioinformatics analysis and a luciferase reporter assay.ResultsHere, we found that miR-153-3p was down-regulated in radioresistant glioma clinical specimens as well as glioma cell lines (U87 and U251) exposed to IR. Enhanced expression of miR-153-3p promoted the radiosensitivity, promoted apoptosis and elevated caspase-3 activity in glioma cells in vitro, as well as the radiosensitivity in U251 cell mouse xenografs in vivo. Mechanically, B cell lymphoma-2 gene (BCL2) was identified as the direct and functional target of miR-153-3p. Moreover, restoration of BCL2 expression reversed miR-153-3p-induced increase of radiosensitivity, apoptosis and caspase-3 activity in U251 cells in vitro. In addition, clinical data indicated that the expression of miR-153-3p was significantly negatively associated with BCL2 in radioresistance of glioma samples.ConclusionsOur findings suggest that miR-153-3p is a potential target to enhance the effect of radiosensitivity on glioma cells, thus representing a new potential therapeutic target for glioma.

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Background As the most common and detrimental brain tumor with high invasiveness and poor prognosis, glioblastoma (GBM) has severely threatened people's health globally. Therefore, it is of great importance and necessary to identify the molecular mechanisms involved in tumorigenesis and development, thus contributing to potential therapeutic targets and strategies. Methods The level of circ_0001588 was detected in 68 pairs of GBM tissues and adjacent normal tissues and human glioma cell lines via a real‐time quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR). Then, the effect of circ_0001588 on the proliferation, migration and invasion of glioma cells was evaluated. In addition, potential downstream targets of circ_0001588 were forecasted by circBANK and Starbase. Their interaction was confirmed by introducing luciferase reporter assays. Moreover, sh‐circ_0001588 transfected U251 cells were used to form tumors in vivo. Finally, the functional mechanism of circ_0001588 was identified by qRT‐PCR, western blotting, xenograft and immunohistochemistry (IHC) assays. Results The expression of circ_0001588 is markedly up‐regulated in GBM tissues and human gliomas cells. Additionally, increased expression of circ_0001588 is positively relevant with poor survival in GBM patients. The down‐regulation of circ_0001588 distinctly inhibits the proliferation, migration and invasion of GBM in vitro, as well as tumor growth in vivo. Moreover, knockdown of circ_0001588 reduces the tumor volume and weight, enhances the relative IHC staining index of E‐cadherin and decreases the relative IHC staining index of Ki‐67, Yin Yang 1 (YY1) and vinmentin in vivo. Mechanistically, circ_0001588 locates in the cytoplasm, which is directly bound with miR‐211‐5p. Furthermore, circ_0001588 can positively regulate YY1 via sponging miR‐211‐5p. Moreover, circ_0001588 accelerates the proliferation, migration and invasion of GBM by modulating miR‐211‐5p/YY1 signaling. Conclusions These results illustrate a new circ_0001588/miR‐211‐5p/YY1 regulatory signaling axis in GBM.

Colorectal cancer (CRC), as a malignant tumor of lower digestive tract, has been found to have an increasing morbidity and mortality in China. It was particularly important to find some earlier biomarkers to predict the risk and prognosis. In this study, several polymorphisms on 3′UTR of three DNA repair genes including MLH3 rs10862, ERCC1 rs3212986, ERCC1 rs735482, ERCC1 rs2336219, and OGG1 rs1052133 were chosen by bioinformatics exploration, and then, a case–control study of 200 CRC cases and controls was performed. Furthermore, a dual‐luciferase assay was also carried out to certify whether the candidate miRNA can regulate its target gene and the selected SNPs have a valid effect on the target miRNA. Finally, both of ERCC1 rs3212986 and MLH3 rs108621 were shown to be associated with the risk of CRC. Comparing with rs3212986 CC genotype, AA was at a higher risk (OR = 3.079, 95% CI: 1.192–7.952). For MLH3 rs108621, comparing with TT genotype, CC and TC were at a higher risk of CRC in male (OR = 5.171, 95% CI: 1.009–26.494; OR = 1.904, 95% CI: 1.049–3.455). Interestingly, an analysis combining both ERCC1 rs3212986 and MLH3 rs108621 also showed an increased risk of CRC. In addition, a dual‐luciferase assay showed that miR‐193a‐3p could regulate MLH3, and the polymorphism rs108621 could alter the miR‐193a‐3p binding to MLH3. Therefore, MLH3 rs108621 may be associated with the risk of CRC due to the effect of miR‐193a‐3p on MLH3, which reminded the possibility as potential susceptibility biomarkers to predict the risk of CRC.