Lin28a attenuates cerebral ischemia/reperfusion injury through regulating Sirt3-induced autophagy.

Cerebral ischemia-reperfusion injury causes damage to local brain tissue and its function, but its specific pathogenesis is still unclear. Autophagy is an important catabolic pathway in eukaryotic cells, which is mainly used to remove damaged intracellular organelles, misfolded long-acting macromolecules and participate in cerebral ischemia-reperfusion injury. Lin28 is a highly conserved RNA-binding protein that plays a role in regulating gene translation, which is important for the growth and maintenance of pluripotent cells. Lin28a has been reported to have a clear protective effect on post-ischemic reperfusion injury of the heart. However, whether Lin28a has an effect on nerve injury after cerebral ischemia-reperfusion needs further study. In this study, we found that the expression of Lin28a was decreased in cerebral ischemia-reperfusion mice model. Upregulation of Lin28a could alleviate the nerve injury caused by ischemia-reperfusion, and promote autophagy of nerve cells. Upregulation of Lin28a reduced nerve cell apoptosis and relieved nerve cell injure induced by oxygen-glucose deprivation/reoxygenation. Lin28a increased the LC3-II levels in nerve cells, suggesting the promotion of autophagy. Mechanism studies indicated that Lin28a promoted autophagy mainly through regulating Sirt3 expression and activating AMPK-mTOR pathway. In conclusion, our study revealed the important role of Lin28a in cerebral ischemia-reperfusion and suggested that Lin28a was a protective factor for cerebral ischemia-induced injury.

miR-138-5p suppresses glioblastoma cell viability and leads to cell cycle arrest by targeting cyclin D3.

Although malignant glioblastoma (GBM) treatment has significantly improved in the past few decades, the prognosis of GBM remains unsatisfactory. MicroRNA (miR)-138-5p has been reported as a tumor suppressor in several types of human cancer; however, little is known about the function of miR-138-5p in GBM. The present study aimed to investigate the role of miR-138-5p in GBM as well as the underlying molecular mechanisms. The present study performed bioinformatics analysis, reverse transcription-quantitative (RT-q)PCR, western blotting, cell viability assays, colony formation assays, invasion assays and cell cycle analysis to investigate the biological function of miR-138-5p in both patient tissues and cell lines. In addition, miR-138-5p targets in GBM were predicted using Gene Expression Omnibus website and further validated by a dual luciferase reporter gene assay. The results revealed that miR-138-5p expression levels in patients with GBM from a Gene Expression Omnibus dataset were significantly downregulated. RT-qPCR analysis of miR-138-5p expression levels also revealed similar results in GBM tissues and cell lines. The upregulation of miR-138-5p expression levels using a mimic significantly inhibited the cell viability, colony formation and the G0/G1 to S progression in GBM cell lines, suggesting that miR-138-5p may be a tumor suppressor. Moreover, miR-138-5p was discovered to directly target cyclin D3 (CCND3), a protein that serves an important role in the cell cycle, and inhibited its expression. Finally, silencing CCND3 using small interfering RNA suppressed the viability of GBM cells. In conclusion, the results of the present study suggested that miR-138-5p may function as a tumor suppressor in GBM by targeting CCND3, indicating that miR-138-5p may be a novel therapeutic target for patients with GBM.

Overexpression miR-486-3p Promoted by Allicin Enhances Temozolomide Sensitivity in Glioblastoma Via Targeting MGMT.

Glioblastoma is the most common primary tumor of the central nervous system that develops chemotherapy resistance. Previous studies showed that Allicin could inhibit multiple cancer cells including glioblastoma, but the function of Allicin in glioblastoma is still unclear. Our work aimed to investigate the underlying molecular mechanism. The results showed that miR-486-3p levels were greatly increased in glioblastoma during Allicin treatment. Overexpression of miR-486-3p increased chemosensitivity to temozolomide (TMZ) in vitro and in vivo. O6-methylguanine-DNA methyltransferase (MGMT) was identified as a direct target of miR-486-3p, and miR-486-3p overexpression prevented the protein translation of MGMT. Moreover, overexpression of MGMT restored miR-486-3p-induced chemosensitivity to TMZ. Taken together, our studies revealed that Allicin could upregulate miR-486-3p and enhance TMZ sensitivity in glioblastoma. The results suggested that in the future, Allicin can be used as an adjuvant therapy with TMZ to improve the prognosis of patients, and miR-486-3p may be a potential target for glioblastoma treatment to improve the curative effects.