miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5.
miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5.
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DOI：
10.3389/fonc.2021.600451
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发表时间：
2021
影响因子：
4.7
通讯作者：
Luo C
中科院分区：
文献类型：
--
作者：
Cui Y;Wang Q;Lin J;Zhang L;Zhang C;Chen H;Qian J;Luo C
新出现的证据表明microRNA（miR）-193a-3p参与各种癌症的肿瘤进展。然而，miR-193 a-3 p在胶质瘤中的生物学功能和精确的分子机制尚未得到很好的证明。因此，本研究主要探讨miR-193 a-3 p在胶质瘤细胞中的抑癌作用及其分子机制。通过qRT-PCR测定胶质瘤组织和细胞系中miR-193 a-3 p的表达。用miR-193 a-3 p模拟物转染U251和U87胶质瘤细胞。使用MTT、集落形成和流式细胞术测定研究miR-193 a-3 p对细胞生长和凋亡的影响。在U87细胞中过表达miR-193 a-3 p也显著抑制了异种移植小鼠模型中的致瘤性并诱导了细胞凋亡。进行荧光素酶测定以确定ALKBH 5是否是胶质瘤细胞中miR-193 a-3 p的直接靶标。采用免疫共沉淀法研究ALKBH 5与RAC丝氨酸/苏氨酸蛋白激酶2（AKT 2）在胶质瘤细胞中的相互作用。miR-193 a-3 p在胶质瘤组织和细胞系中表达下调。miR-193 a-3 p处理抑制U251和U87细胞的增殖并促进凋亡。生物信息学分析和荧光素酶报告基因分析鉴定了一个新的miR-193 a-3 p靶点ALKBH 5。值得注意的是，miR-193 a-3 p转染在胶质瘤细胞中的抗肿瘤作用可能是由于miR-193 a-3 p诱导的由ALKBH 5表达抑制引起的AKT 2表达抑制。此外，免疫沉淀表明，ALKBH 5在胶质瘤细胞中通过RNA非依赖性机制与AKT 2物理相互作用。miR-193 a-3 p直接靶向ALKBH 5，通过抑制AKT 2途径抑制胶质瘤细胞生长并促进胶质瘤细胞凋亡，ALKBH 5和AKT 2之间的物理相互作用是通过上调miR-193 a-3 p抑制胶质瘤细胞凋亡的关键。我们的研究表明miR-193 a-3 p对胶质瘤细胞的抗肿瘤作用是由于ALKBH 5介导AKT 2诱导的内在凋亡信号通路。
Emerging evidence indicates that microRNA (miR)-193a-3p is involved in the tumor progression of various cancers. However, the biological functions and precise molecular mechanisms of miR-193a-3p in gliomas have not been well documented. Accordingly, this study focused on the tumor suppressor role and molecular mechanisms of miR-193a-3p in glioma cells. miR-193a-3p expression was determined by qRT-PCR in glioma tissues and cell lines. U251 and U87 glioma cells were transfected with a miR-193a-3p mimic. The effects of miR-193a-3p on cell growth and apoptosis were investigated using MTT, colony-forming, and flow cytometry assays. Overexpression of miR-193a-3p in U87 cells also significantly suppressed tumorigenicity and induced apoptosis in the xenograft mouse model. Luciferase assays were conducted to determine if ALKBH5 is a direct target of miR-193a-3p in glioma cells. Immunoprecipitation was used to explore the interaction between ALKBH5 and RAC-serine/threonine-protein kinase 2 (AKT2) in glioma cells. miR-193a-3p was downregulated in glioma tissues and cell lines. miR-193a-3p treatment suppressed proliferation and promoted apoptosis in both U251 and U87 cells. Bioinformatics analysis and luciferase reporter assay identified a novel miR-193a-3p target, ALKBH5. Notably, the antitumor effect of miR-193a-3p transfection in glioma cells may be due to the miR-193a-3p–induced inhibition of AKT2 expression caused by the suppression of ALKBH5 expression. Furthermore, immunoprecipitation indicated that ALKBH5 physically interacted with AKT2 through an RNA-independent mechanism in glioma cells. miR-193a-3p directly targets ALKBH5 to inhibit the growth and promote the apoptosis of glioma cells by suppressing the AKT2 pathway both in vitro and in vivo, and the physical interaction between ALKBH5 and AKT2 is essential for suppressing cell apoptosis by upregulating miR-193a-3p in glioma cells. Our study revealed that the antitumor effects of miR-193a-3p on glioma cells is due to ALKBH5 mediation of the AKT2-induced intrinsic apoptosis signaling pathway.
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miR-193a-3p 和 miR-193a-5p 分别通过下调 Rab27B 和 SRR 抑制人骨肉瘤细胞的转移。
影响因子：
4
作者：
Pu Y;Zhao F;Cai W;Meng X;Li Y;Cai S
通讯作者：
Cai S
MiR-193a-3p 是肺癌中重要的肿瘤抑制因子并直接靶向 KRAS
影响因子：
--
作者：
Fan, Qian;Hu, Xiuting;Ba, Yi
通讯作者：
Ba, Yi
影响因子：
3.3
作者：
Mamoori, Afraa;Wahab, Riajul;Lam, Alfred King-yin
通讯作者：
Lam, Alfred King-yin
DOI：
10.3322/caac.20069
发表时间：
2010-05
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Van Meir EG;Hadjipanayis CG;Norden AD;Shu HK;Wen PY;Olson JJ
通讯作者：
Olson JJ
影响因子：
2.9
作者：
Liu Y;Xu X;Xu X;Li S;Liang Z;Hu Z;Wu J;Zhu Y;Jin X;Wang X;Lin Y;Chen H;Mao Y;Luo J;Zheng X;Xie L
通讯作者：
Xie L