Glioblastoma is highly resistant to radiation therapy. The underlying molecular mechanism is not completely understood. The DNA damage response (DDR) pathway plays a crucial role in radioresistance of glioablastoma cells. Growing evidence has demonstrated that radiation induces alterations in microRNA (miR) profiles. However, how radiation induces specific miRs and how they might regulate the DDR remain elusive. In our study, we found that radiation induced c-jun transcription of miR-221 and miR-222. miR-221 and miR- 222 modulated DNA-PKcs expression to affect DNA damage repair by activating Akt independent of PTEN status. Knocking down of miR-221/222 significantly increased radiosensitivity of glioblastoma cells. Inhibition of Akt by RNAi or LY294002 treatment may overcome miR-221/222 induced radioresistance. Notably, combined anti-miR-221/222 and radiotherapy has remarkably inhibited tumor growth compared with anti-miR-221/222 or radiotherapy alone in a subcutaneous mouse model. Our results suggest that radio-induced c-jun promotes transcription of miR-221/222, which mediates DNA damage repair of glioblastoma cells independent of PTEN. These data indicate for the first time that miR-221/222 play an important role in mediating radio-induced DNA damage repair and that miR-221/222 could serve as potential therapeutic targets for increasing radiosensitivity of glioblastoma cells.

The long non-coding (lnc)RNA named tissue differentiation inducing non-protein coding RNA (TINcR) is a tumor marker that has not been studied in breast cancer. The present study aimed to investigate the TINcR-targeting micro (mi)RNAs and the regulatory mechanisms of TINcR in breast cancer. Following prediction by TargetScan and confirmation by dual-luciferase reporter assay, TINcR was demonstrated to be a target gene for miR-589-3p. The expression of TINcR and miR-589-3p in breast cancer and adjacent tissues was detected by reverse transcription-quantitative (RT-q)PcR, and the correlation between TINcR and miR-589-3p expression was determined by using Spearman correlation analysis. The 5-years survival was analyzed in patients with breast cancer according to TINcR expression (high or low). The effects of TINcR and miR-589-3p on the proliferation, apoptosis, migratory and invasive abilities of some breast cancer cell lines were detected by MTT assay, flow cytometry, wound healing assay and Transwell assay. The target gene of miR-589-3p was predicted and verified by TargetScan and dual-luciferase reporter assay, and the mechanism of miR-589-3p involvement in breast cancer cells was explored by overexpression or downregulation of miR-589-3p in breast cancer cells. RT-qPcR and western blotting were used to determine the expression of the insulin-like growth factor 1 receptor (IGF1R)/AKT pathway-related genes. The results demonstrated that TINcR expression level was negatively correlated with miR-589-3p expression level in breast cancer tissues and that patients with high expression of TINcR presented with lower survival rates. In addition, TINcR overexpression in cancer cells inhibited miR-589-3p expression, and cell transfection with miR-589-3p mimic partially reversed the effect of TINcR overexpression on the promotion of cancer cell proliferation, migration and invasion, and on the inhibition of cancer cell apoptosis. Furthermore, IGF1R, which is a target gene of miR-589-3p, increased cancer cell proliferation, migration and invasion and inhibited cancer cell apoptosis; however, these effects were partially reversed by miR-589-3p mimic. Furthermore, the results demonstrated that miR-589-3p mimic could downregulate the protein expression of IGF1R and p-AKT. In addition, TINcR overexpression downregulated miR-589-3p expression level. miR-589-3p partially reversed the effects of TINcR overexpression on cancer cell proliferation, migration and invasion, and inhibited cancer cell apoptosis by inhibiting the IGF1R-Akt pathway. The results from the present study demonstrated that TINcR may sponge miR-589-3p in order to inhibit IGF1R-Akt pathway activation in breast cancer cells, promoting therefore cancer cell proliferation, migration and invasion.

p53 is the most highly mutated tumor suppressor in human malignancies. A wide array of p53 mutations has been revealed to play pivotal roles during cancer progression, which abolish anti-tumor functions of wild type p53 but also elicit tumorigenic effects by activating a diverse subset of downstream molecules. R273H mutation of p53 has been closely implicated in human cancer. Here we report miR-30a as a novel downstream target of p53 R273H mutant, which binds to the promoter region to repress miR-30a expression. Consequently, p53 R273H mutant enhances the migratory capabilities of tumor cells that are compromised by exogenous miR-30a over-expression. Our further investigation indicates that p53 R273H mutation unleashes the inhibition effect of miR-30a on IGF-1R expression, thus leading to elevated activation of IGF-1R-AKT signaling cascade in tumor cells.

Objective: To investigate the clinical efficacy and safety of endoscopic thyroidectomy through the oral vestibular approach and the breast approach. Methods: Retrospective analysis was done on clinical data of 80 patients who received an endoscopic thyroidectomy from April 2018 to March 2019. The research group had endoscopic thyroidectomy through the oral vestibular approach, whereas the control group had endoscopic thyroidectomy through the areola breast approach. Comparison between the two groups including intraoperative bleeding, operation time, total postoperative drainage, drainage time, postoperative sustained pain time, recovery feeding time, postoperative hospitalization duration, satisfactory esthetic outcomes of incision, central lymph node clearance, skin injury, infection incidence, and complications such as facial hematoma, subcutaneous emphysema, abnormal feeling of the neck and chest, and pleural injury was recorded. Results: There was no significant difference between the two groups in the amount of intraoperative bleeding, operation time, total postoperative drainage, drainage time, postoperative sustained pain time, recovery feeding time, and postoperative hospitalization time (P > .05). The incidence of complications such as skin injury, infection, wound hematoma, subcutaneous emphysema, abnormal feeling of the neck and chest, and pleural injury was not statistically different between the two groups (P > .05). There was no significant difference in the number of lymph nodes cleaned in the central area between the two groups (P > .05). The overall satisfaction of the patients with the cosmetic effects of the incision (100.00%) was higher than that of the control group (90.00%). Conclusions:The clinical treatment effect and safety in the two groups were similar, but the transoral group had better cosmetic effects.

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