Long Noncoding RNA-GAS5 Inhibits The Progression Of Glioma By Downregulating The Expression Of MicroRNA-10b And Sirtuin 1

AimGliomas are the most common intracranial primary brain tumors,accounting for 80% of malignant tumor of the brain,and have a high fatality rate.Aggressive growth is its characteristic.Glioblastomas often have unclear boundaries with surrounding normal brain tissue.The brain tissue around the tumor is severely edema and difficult to identify during surgery.It makes it difficult to completely remove the diseased tissue by surgery.It is easy to relapse after resection.At present,the conventional method of treating glioma is based on surgery to maximize the removal of the tumor,supplemented by radiation therapy and chemotherapy.In the occurrence and development of glioblastoma,oncogenes and tumor suppressor genes play a vital role,and they are multi-stage complex processes involving multiple genes.Glioma has a high mortality rate and a poor prognosis.With the improvement of living standards and medical conditions,including surgery-based,radiotherapy,chemotherapy,new biological treatment and other treatment methods,the prognosis of glioma is still poor.The basic research of glioblastoma provides some new treatment strategies.Long non-coding RNAs(Growth arrest specific transcript 5,GAS5)appear to act as tumor suppressor genes,which are low-expressed in a variety of tumor tissues,which is to promote tumor growth,invasion and metastasis,and reduce the sensitivity of cells to chemotherapy drugs.MicroRNA-10b(miR-10b)is dysregulated in some cancers,and plays an important role in invasion and metastasis.However,there is no evidence to prove that GAS5 and miR-10 b are related in the occurrence and development of glioblastoma.Therefore,the purpose of this study was to explore the biological role of GAS5-miR-10 b node in glioblastoma cells.MethodsWe artificially interfered with the expression level of GAS5 by transfection to promote GAS5 overexpression or silence it in glioma cells,and then carried out the next experiment to determine the cell proliferation ability by using cell counting kit 8(CCK-8)The cell migration and invasion ability was determined by Transwell chamber experiment,and the cell apoptosis was measured by flow cytometry.The protein imprint analysis was also performed.Quantification of miR-10 b and Sirtuin 1(Sirt1)by qRT-PCR.After the above experiments,we analyzed the proliferation,migration,invasion,and apoptosis of glioma cells after Lncrna gas5 overexpression and silencing.And Western blot was used to detect the phosphorylated forms of PTEN,PI3 K,AKT,MEK and ERK.Further analysis of gas5 may affect the possible pathways of glioma cell biological processes.ResultsIn our current experimental study,we demonstrated that GAS5 overexpression inhibits the growth of human glioma U251 and A172 cells by down-regulating miR-10 b.In addition,we found that the expression of Sirt1 is suppressed by GAS5 via the expression of miR-10 b that is suppressed.Futher more,We also demonstrated that Sirt1 is involved in the regulation of PTEN/PI3K/AKT and MEK/ERK,suggesting that inhibition of Sirt1 expression may be important in the anti-glioma by enhancing PTEN or inactivating the PI3K/AKT and MEK/ERK transduction cascade.ConclusionLncrna GAS5 inhibits the process of glioma cells by reducing miR-10 b,and is accompanied by Sirt1 silencing-induced inactivation of the PTEN/PI3K/AKT and MEK/ERK cascades.