中国癌症防治杂志2025，Vol.17Issue(4)：483-489,7.DOI:10.3969/j.issn.1674-5671.2025.04.13
lncRNA ATP2C2-AS1通过调控PI3K/Akt/mTOR信号通路对骨肉瘤细胞增殖、凋亡的影响
Effects of lncRNA ATP2C2-AS1 on the proliferation and apoptosis of osteosarcoma cells by regulating PI3K/Akt/mTOR signaling pathway
摘要
Abstract
Objective To investigate the effects of the long non-coding RNA(lncRNA)ATPase secretory pathway Ca2+transporting 2 antisense RNA 1(ATP2C2-AS1)on the proliferation andapoptosis of osteosarcoma cells,as well as to elucidate its underlying mechanism.Methods The expression levels of ATP2C2-AS1 in human normal osteoblasts cell(hFOB 1.19)and human osteosarcoma cell lines(Saos-2,U2OS,143B,and HOS)were quantified using qRT-PCR.Saos-2 osteosarcoma cells were transfected with either an ATP2C2-AS1 siRNA(si-ATP2C2-AS1)and its negative control(si-NC),as well as ATP2C2-AS1 overexpression plasmid(oe-ATP2C2-AS1)or its negative control(Vector).Following the assessment of transfection efficiency,the PI3K inhibitor(NVP-BEZ235)was used to Saos-2 cells trans-fected with either the Vector or oe-ATP2C2-AS1.Cell proliferation activity was measured using the cell counting kit-8(CCK-8)method,while apoptosis levels were assessed via flow cytometry.Western blot was used to detect the expression levels of apoptosis-related proteins(Bax,Bcl-2,and Cleaved-caspase-3)and proteins associated with the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mam-malian target of rapamycin(mTOR)signaling pathway.Results Compared with hFOB 1.19 cells,the expression levels of ATP2C2-AS1 were markedly elevated in Saos-2,U2OS,143B and HOS cell lines(all P＜0.001),with the most pronounced expression observed in Saos-2 cells.The silencing of ATP2C2-AS1 reduced the proliferation activity in Saos-2 cells,an increase cell apoptosis,and a downregulation of PI3K(p85α),Bcl-2 protein,and the p-Akt/Akt and p-mTOR/mTOR proteins ratios,while it upregulated the expression of Bax and Cleaved-caspase-3 proteins(all P＜0.05).Conversely,the overexpression of ATP2C2-AS1 enhanced the proliferation activity of Saos-2 cells,inhibited apoptosis,and led to an upregulation of PI3K(p85α),Bcl-2 protein,and the ratios of p-Akt/Akt and p-mTOR/mTOR protein ratios,while downregulating the expression of Bax and Cleaved-caspase-3 proteins(all P＜0.05).The intervention with NVP-BEZ235 significantly counteracted the proliferation effects of ATP2C2-AS1 overexpression in Saos-2 cells,and induced apoptosis.Conclusions ATP2C2-AS1 may promote the proliferation and inhibit the apoptosis of osteosarcoma cells through the activation of the PI3K/Akt/mTOR signaling pathway.关键词
骨肉瘤/ATP酶分泌途径钙离子转运蛋白2/长链非编码RNA/增殖/凋亡Key words
Osteosarcoma/ATPase secretory pathway Ca2+transporting 2/Long non-coding RNA/Proliferation/Apoptosis分类
医药卫生引用本文复制引用
李燕霞,代辉,陈佳,魏传可,邹秀淇,邓海波..lncRNA ATP2C2-AS1通过调控PI3K/Akt/mTOR信号通路对骨肉瘤细胞增殖、凋亡的影响[J].中国癌症防治杂志,2025,17(4):483-489,7.基金项目
华中科技大学同济医学院附属梨园医院院内科学研究基金项目(2024LYYYLCYJ0008) （2024LYYYLCYJ0008）
