MicroRNA-205 suppresses the growth of adrenocortical carcinoma SW-13 cells via targeting Bcl-2
MicroRNA-205 suppresses the growth of adrenocortical carcinoma SW-13 cells via targeting Bcl-2
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MicroRNA-205 通过靶向 Bcl-2 抑制肾上腺皮质癌 SW-13 细胞的生长。
DOI：
10.3892/or.2015.4295
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发表时间：
2015-12-01
期刊：
影响因子：
4.2
通讯作者：
Chen, Shuai
中科院分区：
文献类型：
--
作者：
Wu, Yigao;Wang, Wei;Chen, Shuai
与肾上腺皮质腺瘤(ACA)相比，肾上腺皮质癌(ACC)预后非常差，治疗选择有限。此外，区分ACC和ACA的传统方法也可能很困难。目前，还没有足够可靠的分子病理标记物来区分这两种肿瘤。最近，越来越多的数据表明miRNAs在肿瘤相关过程中是至关重要的调节因子。在本研究中，我们发现与ACAs相比，miR-205在ACC组织中的表达明显受到抑制，这在体外诱导了ACC SW-13细胞的凋亡，损害了细胞的增殖，并抑制了体内肿瘤的生长。利用生物信息学预测，通过3‘-非翻译区(3’-UTR)的相互作用，确定了Bcl2是miR-205的靶点。荧光素酶分析、qRT-PCR、免疫组织化学分析和Western blotting证实，Bcl2的表达与miR-205呈负相关。进一步的机制研究发现，Bcl2的激活可裂解Bax，释放参与细胞凋亡的caspase-9和caspase-3，最终诱导Sw-13细胞的凋亡。结论：miR-205通过靶向抗凋亡基因Bcl-2抑制ACC SW-13细胞的生长。
Compared to adrenocortical adenoma (ACA), adrenocortical carcinoma (ACC) has very poor prognosis and limited treatment options. Also conventional methods to distinguish ACC from ACA can be difficult. At this time, no molecular pathological markers are reliable enough to distinguish either tumor. Recently, increasing data have indicated miRNAs to be crucial regulators in the tumor‑related processes. In the present study, we found that miR-205 expression is significantly suppressed in ACC tissues compared with ACAs, and that this induces apoptosis and impairs proliferation of ACC SW-13 cells in vitro as well as inhibits tumor growth in vivo. Using bioinformatic predictions, Bcl-2 was identified to be a target of miR-205 via 3'-untranslated region (3'UTR) interactions, which was confirmed by luciferase assay, qRT-PCR, immunohistochemical assay and western blotting showing that mRNA and protein expression of Bcl-2 were negatively related to miR-205. Further investigation into the mechanism found that activation of Bcl-2 cleaved Bax, releasing caspase-9 and -3 that are involved in the intrinsic apoptosis pathway, eventually inducing SW-13 cell apoptosis. In conclusion, miR-205 suppresses the growth of ACC SW-13 cells via targeting the anti-apoptotic gene Bcl-2.