RGS19基因敲低对胶质母细胞瘤增殖的影响及其机制OA

Objective To investigate the role of G protein signaling regulator(RGS19)in the proliferation and apoptosis of glioblas-toma(GBM)and its underlying molecular mechanism.Methods GEPIA database was used to analyze the expression of RGS19 in GBM tissues and its association with patient prognosis.U251 cell lines with RGS19 gene knockdown or overexpression were con-structed.Colony formation assay and EdU assay were used to evaluate cell proliferation,TUNEL staining was used to assess cell apop-tosis,Western blot was used to analyze expression levels of related proteins,and double fluorescence autophagic flux technology was used to detect cellular autophagy.Furthermore,the autophagy agonist Rapamycin was used to activate autophagy and examine the mediating role of autophagy in RGS19-regulated cell proliferation and apoptosis.Additionally,a nude mouse subcutaneous xenograft tumor model was established to investigate the inhibitory effect of RGS19 gene knockdown on tumor growth in vivo.Results RGS19 expression was significantly increased in GBM tissues and cell lines(P<0.05),and it was positively correlated with poor prognosis(P<0.05).Knock-down of RGS19 gene significantly inhibited the proliferation capacity and colony formation ability of U251 cells(P<0.01),and induced cell apoptosis(P<0.01).Furthermore,RGS19 gene knockdown also inhibited autophagic activity(P<0.01),manifested by decreased LC3-Ⅱ/LC3-Ⅰ protein expressions and increased p62 protein expression(P<0.01).Rapamycin partially reversed the inhibition of cell proliferation and the increase of apoptosis caused by RGS19 gene knockdown(P<0.05).Conversely,the overexpression of RGS19 gene significantly inhibited cell apoptosis and enhanced LC3-Ⅱ/LC3-Ⅰ(P<0.05).The subcutaneous xenograft tumor model in nude mice further confirmed that the tumor volume in RGS19 knockdown group was significantly reduced compared with negative control group(P<0.01).Conclusion RGS19 gene knockdown can significantly inhibit the tumor growth by inhibiting the autophagic activity of tumor cells,suggesting that RGS19 is a potential new therapeutic target for GBM.