miR-199a-5p inhibits proliferation and induces apoptosis in hemangioma cells through targeting HIF1A.
miR-199a-5p inhibits proliferation and induces apoptosis in hemangioma cells through targeting HIF1A.
复制标题
miR-199a-5p通过靶向HIF1A抑制血管瘤细胞增殖并诱导细胞凋亡
DOI：
10.1177/0394632017749357
复制
发表时间：
2018-01
影响因子：
3.5
通讯作者：
Ou JM
中科院分区：
文献类型：
--
作者：
Wang Y;Dai YX;Wang SQ;Qiu MK;Quan ZW;Liu YB;Ou JM
MicroRNAs(MiRNAs)在调节血管生成和肿瘤进展中起着至关重要的作用，其中miR-199a-5p(miR-199a)已被报道在多种恶性肿瘤中发挥肿瘤抑制作用。然而，血管瘤(HAS)中miR-199a的确切机制仍不清楚。在本研究中，我们发现miR-199a在增殖期HAS组织中低表达，而增殖细胞核抗原(PCNA)在增殖期HAS组织中高表达。Spearman相关分析显示，增生期HAS中miR-199a与增殖细胞核抗原表达呈负相关。体外实验表明，miR-199a的修复抑制了HA来源的内皮细胞(HDEC)和CRL-2586 EOMA细胞的增殖能力，诱导了细胞的凋亡，同时降低了增殖细胞核抗原的表达，增加了caspase-3的表达，而miR-199a的抑制剂则逆转了这些作用。此外，HIF1a被认为是miR-199a的靶点，并且与增殖期HAS中miR-199a的表达呈负相关。HIF1a的过表达减弱了miR-199a在HAS细胞中的抗增殖作用。综上所述，我们的发现表明miR-199a可能通过靶向HIF1a抑制HAS细胞的增殖和诱导其凋亡，为HAS提供了一个潜在的治疗靶点。
MicroRNAs (miRNAs) exhibit a crucial role in the regulation of angiogenesis and tumor progression, of which miR-199a-5p (miR-199a) has been reported to function as a tumor suppressor in multiple malignancies. However, the precise mechanisms underlying miR-199a in hemangiomas (HAs) remain elusive. In this study, we found that miR-199a had low expression level, while proliferating cell nuclear antigen (PCNA) had high expression level in proliferating-phase HAs compared with the involuting-phase HAs and normal tissues. Spearman correlation analysis revealed the negative correlation of miR-199a with PCNA expression in proliferating-phase HAs. In vitro experiments showed that restoration of miR-199a suppressed cell proliferation capability and induced cell apoptosis in HA-derived endothelial cells (HDEC) and CRL-2586 EOMA cells, followed with decreased PCNA expression and increased cleaved caspase-3 expression, but miR-199a inhibitor reversed these effects. Furthermore, HIF1A was identified as a target of miR-199a and had negative correlation with miR-199a expression in proliferating-phase HAs. Overexpression of HIF1A attenuated the anti-proliferation effect of miR-199a mimic in HAs cells. Taken together, our findings demonstrate that miR-199a may inhibit proliferation and induce apoptosis in HAs cells via targeting HIF1A and provide a potential therapeutic target for HAs.
登录
查看更多内容
MicroRNA-199a-5p 通过双靶向 PIAS3 和 p27 促进人骨肉瘤中的肿瘤生长。
影响因子：
4.6
作者：
Wang C;Ba X;Guo Y;Sun D;Jiang H;Li W;Huang Z;Zhou G;Wu S;Zhang J;Chen J
通讯作者：
Chen J
影响因子：
8.8
作者：
Sakaguchi T;Yoshino H;Yonemori M;Miyamoto K;Sugita S;Matsushita R;Itesako T;Tatarano S;Nakagawa M;Enokida H
通讯作者：
Enokida H
影响因子：
--
作者：
Kuninty PR;Bojmar L;Tjomsland V;Larsson M;Storm G;Östman A;Sandström P;Prakash J
通讯作者：
Prakash J
MiR-199a-5p 与恶性肿瘤呈负相关，并通过靶向肝癌中的己糖激酶 2 来调节糖酵解和乳酸的产生
影响因子：
13.5
作者：
Guo, Weijie;Qiu, Zhaoping;He, Xianghuo
通讯作者：
He, Xianghuo
影响因子：
4.8
作者：
Gordillo, Gayle M.;Biswas, Ayan;Sen, Chandan K.
通讯作者：
Sen, Chandan K.