MicroRNA miR-491-5p targeting both TP53 and Bcl-XL induces cell apoptosis in SW1990 pancreatic cancer cells through mitochondria mediated pathway.
MicroRNA miR-491-5p targeting both TP53 and Bcl-XL induces cell apoptosis in SW1990 pancreatic cancer cells through mitochondria mediated pathway.
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靶向 TP53 和 Bcl-XL 的 MicroRNA miR-491-5p 通过线粒体介导的途径诱导 SW1990 胰腺癌细胞凋亡
DOI：
10.3390/molecules171214733
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发表时间：
2012-12-11
期刊：
影响因子：
--
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Guo R;Wang Y;Shi WY;Liu B;Hou SQ;Liu L
microRNA（miRNA）积极参与广泛的细胞过程，如增殖、分化、细胞存活和凋亡。miRNA的表达失调可能会影响细胞生长并最终导致癌症。在这项研究中，我们发现hsa-miR 491 - 5 p（miR 491 - 5 p）在正常人胰腺组织中的表达水平显著高于胰腺癌细胞。靶向位点预测表明，Bcl-XL和TP 53在其3'UTR中都含有miR-491- 5 p识别位点。miR-491- 5 p在胰腺癌细胞系SW 1990中的过表达有效地抑制内源性Bcl-XL和TP 53基因的表达。两个靶基因的种子匹配区域的突变进一步证实了miR 491 - 5 p识别的特异性。细胞增殖率与miR-491- 5 p剂量增加呈负相关。流式细胞仪分析显示，随着miR 491 - 5 p剂量的增加，总凋亡和早期凋亡细胞的比例显著诱导。此外，一项机制研究表明，miR-R491- 5 p介导的细胞凋亡与内在线粒体介导的途径的激活有关。miR 491 - 5 p还显著抑制促有丝分裂信号通路如STAT 3和PI-3 K/Akt，但不抑制Ras/MAPK。因此，我们的结果表明，miR 491 - 5 p可以有效地靶向Bcl-xL和TP 53，并诱导细胞凋亡，而不依赖于TP 53。
MicroRNA (miRNA) actively participates in a broad range of cellular processes such as proliferation, differentiation, cell survival and apoptosis. Deregulated expression of miRNA may affect cell growth and eventually lead to cancer. In this study, we found that hsa-miR491-5p (miR491-5p) displays a significantly high level of expression in normal human pancreas tissue versus pancreatic cancer cells. Targeted site prediction indicated that both Bcl-XL and TP53 contain miR-491-5p recognizing sites in their 3' UTRs. Overexpression of miR-491-5p in the pancreatic cancer cell line SW1990 effectively inhibited both endogenous Bcl-XL and TP53 gene expressions. Mutagenesis at the seed match region of both targeted genes further confirmed the specificity of miR491-5p recognition. Cell proliferation rate was inversely related to the increased doses of miR-491-5p. Flow cytometric analysis showed that the proportions of total apoptotic and early apoptotic cells were significantly induced as the dose of miR491-5p increased. Moreover, a mechanistic study indicated that miR-R491-5p-mediated cell apoptosis was associated with the activation of intrinsic mitochondria mediated pathways. miR491-5p also markedly inhibited mitogenic signaling pathways such as STAT3 and PI-3K/Akt, but not Ras/MAPK. Thus, our results demonstrated that miR491-5p could effectively target both Bcl-xL and TP53 and induce cell apoptosis independent of TP53.
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