Tumor suppressor role of miR-3622b-5p in ERBB2-positive cancer.
Tumor suppressor role of miR-3622b-5p in ERBB2-positive cancer.
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miR-3622b-5p 在 ERBB2 阳性癌症中的抑癌作用
DOI：
10.18632/oncotarget.14968
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发表时间：
2017-04-04
期刊：
影响因子：
--
通讯作者：
Liu P
中科院分区：
文献类型：
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作者：
Lu M;Wang T;He M;Cheng W;Yan T;Huang Z;Zhang L;Zhang H;Zhu W;Zhu Y;Liu P
ERBB 2的过度表达或扩增在多种癌症中观察到。然而，ERBB 2阳性癌症中ERBB 2下调的分子机制仍然不清楚。本实验研究了miR-3622 b-5 p在ERBB 2阳性乳腺癌和胃癌中的抑制作用。在HEK-293 T、SK-BR-3和MCF-10A细胞中构建的ERBB 2 3′-非翻译区报告基因的荧光素酶活性表明，ERBB 2是miR-3622 b-5 p的靶基因。过表达miR-3622 b-5 p可降低ERBB 2蛋白水平，减弱mTORC 1/S6的激活，诱导ERBB 2阳性癌细胞凋亡。miR-3622 b-5 p在乳腺癌和胃癌组织中显著下调。ERBB 2阳性乳腺癌和胃癌组织中的这种下调作用比ERBB 2阴性乳腺癌和胃癌组织中的下调作用更明显。miR-3622 b-5 p使ERBB 2阳性癌细胞更容易受到顺铂和5-氟尿嘧啶诱导的凋亡的影响。综上所述，miR-3622 b-5 p通过靶向ERBB 2/mTORC 1信号通路参与人ERBB 2阳性癌细胞的增殖和凋亡。
Over-expression or amplification of ERBB2 is observed in multifarious carcinomas. However, the molecular mechanism of ERBB2 downregulation in ERBB2-positive cancers remains obscure. This experiment investigated the suppressive role of miR-3622b-5p in ERBB2-positive breast and gastric cancers. The luciferase activity of ERBB2 3′-untranslated region-based reporters constructed in HEK-293T, SK-BR-3 and MCF-10A cells suggested that ERBB2 was the target gene of miR-3622b-5p. Over-expressed miR-3622b-5p reduced the protein level of ERBB2, weakened the activation of mTORC1/S6, and induced the apoptosis of ERBB2-positive cancer cells. MiR-3622b-5p was significantly down-regulated in breast and gastric cancer tissues. This down-regulation in ERBB2-positive breast and gastric cancer tissues was more obvious than that in ERBB2-negative breast and gastric cancer tissues. MiR-3622b-5p turned ERBB2-positive cancer cells more vulnerable to the apoptosis induced by cisplatin and 5-fluorouracil. Taken together, miR-3622b-5p is involved in the proliferation and apoptosis of human ERBB2-positive cancer cells via targeting ERBB2/mTORC1 signaling pathway.