MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN.
MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN.
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MicroRNA-221和microRNA-222通过靶向PTEN调节胃癌细胞增殖和放射抗性。
DOI：
10.1186/1471-2407-10-367
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发表时间：
2010-07-12
期刊：
影响因子：
3.8
通讯作者：
Chun-Sheng K
中科院分区：
文献类型：
--
作者：
Chun-Zhi Z;Lei H;An-Ling Z;Yan-Chao F;Xiao Y;Guang-Xiu W;Zhi-Fan J;Pei-Yu P;Qing-Yu Z;Chun-Sheng K
microRNA（miRNAs）可以作为癌基因或抑癌基因通过调节细胞增殖和/或凋亡发挥作用。发现miR-221和miR-222在各种人类恶性肿瘤中通过直接靶向p27和p57来诱导细胞生长和细胞周期进展。然而，miR-221和miR-222在人类胃癌中的作用尚未报道。在这项研究中，我们研究了miR-221和miR-222对人胃癌细胞的影响，并确定了可能介导其生物学的miR-221和miR-222的靶基因。用AS-miR-221/222转染人胃癌细胞系SGC 7901，或用pMSCV-miR-221/222转导人胃癌细胞系SGC 7901，分别敲低或恢复miR-221和miR-222的表达。然后通过细胞活力、细胞周期分析、细胞凋亡、transwell和克隆形成测定来评估miR-221和miR-222的作用。通过Western blot和荧光素酶报告基因分析鉴定潜在的靶基因。上调miR-221和miR-222可诱导SGC 7901细胞的恶性表型，而敲低miR-221和miR-222可通过诱导PTEN表达逆转该表型。此外，miR-221和miR-222的敲除抑制了胃癌细胞的生长和侵袭，并增加了胃癌细胞的放射敏感性。值得注意的是，miR-221和miR-222的种子序列与PTEN的3 'UTR相匹配，并且将不具有3' UTR的PTEN cDNA引入SGC 7901细胞中消除了miR-221和miR-222诱导的恶性表型。PTEN-3 'UTR荧光素酶报告基因分析证实了PTEN是miR-221和miR-222的直接靶点。这些结果表明，miR-221和miR-222可能通过直接调节PTEN表达来调节SGC 7901细胞的放射敏感性、细胞生长和侵袭。我们的研究表明，抑制miR-221和miR-222可能形成一种新的治疗人类胃癌的策略。
MicroRNAs (miRNAs) can function as either oncogenes or tumor suppressor genes via regulation of cell proliferation and/or apoptosis. MiR-221 and miR-222 were discovered to induce cell growth and cell cycle progression via direct targeting of p27 and p57 in various human malignancies. However, the roles of miR-221 and miR-222 have not been reported in human gastric cancer. In this study, we examined the impact of miR-221 and miR-222 on human gastric cancer cells, and identified target genes for miR-221 and miR-222 that might mediate their biology. The human gastric cancer cell line SGC7901 was transfected with AS-miR-221/222 or transduced with pMSCV-miR-221/222 to knockdown or restore expression of miR-221 and miR-222, respectively. The effects of miR-221 and miR-222 were then assessed by cell viability, cell cycle analysis, apoptosis, transwell, and clonogenic assay. Potential target genes were identified by Western blot and luciferase reporter assay. Upregulation of miR-221 and miR-222 induced the malignant phenotype of SGC7901 cells, whereas knockdown of miR-221 and miR-222 reversed this phenotype via induction of PTEN expression. In addition, knockdonwn of miR-221 and miR-222 inhibited cell growth and invasion and increased the radiosensitivity of SGC7901 cells. Notably, the seed sequence of miR-221 and miR-222 matched the 3'UTR of PTEN, and introducing a PTEN cDNA without the 3'UTR into SGC7901 cells abrogated the miR-221 and miR-222-induced malignant phenotype. PTEN-3'UTR luciferase reporter assay confirmed PTEN as a direct target of miR-221 and miR-222. These results demonstrate that miR-221 and miR-222 regulate radiosensitivity, and cell growth and invasion of SGC7901 cells, possibly via direct modulation of PTEN expression. Our study suggests that inhibition of miR-221 and miR-222 might form a novel therapeutic strategy for human gastric cancer.
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DOI：
10.1111/j.1440-1746.2008.05666.x
发表时间：
2009-04-01
影响因子：
4.1
作者：
Guo, Junming;Miao, Ying;Wang, Yanjun
通讯作者：
Wang, Yanjun
影响因子：
2.6
作者：
Ge, H.;Cao, Y. Y.;Zhang, J. H.
通讯作者：
Zhang, J. H.
影响因子：
3.5
作者：
Cinti, Caterina;Vindigni, Carla;Tosi, Piero
通讯作者：
Tosi, Piero
影响因子：
6.4
作者：
Byun, DS;Cho, K;Chi, SG
通讯作者：
Chi, SG
影响因子：
50.3
作者：
Garofalo M;Di Leva G;Romano G;Nuovo G;Suh SS;Ngankeu A;Taccioli C;Pichiorri F;Alder H;Secchiero P;Gasparini P;Gonelli A;Costinean S;Acunzo M;Condorelli G;Croce CM
通讯作者：
Croce CM