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miRNA-182 通过其对人皮质肌动蛋白相关蛋白的作用抑制人肺腺癌细胞的增殖和侵袭。

microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein.

机构信息

Huadong Hospital Affiliated to Fudan University, Shanghai 200040, PR China.

出版信息

Int J Mol Med. 2011 Sep;28(3):381-8. doi: 10.3892/ijmm.2011.679. Epub 2011 Apr 18.

DOI:10.3892/ijmm.2011.679
PMID:21503569
Abstract

Lung cancer is one of the main causes of cancer death worldwide. The cortactin gene, CTTN, may play a pivotal role in the proliferation and invasion of tumors. A microRNA (miR-182) was cloned and used to study the expression of CTTN and its regulatory effects on the proliferation and invasion of the lung cancer cell line, A549. Cortactin protein and CTTN mRNA expression decreased in A549 cells that were transfected with the miR-182 expression plasmid. A cell proliferation assay indicated that miR-182 expression affected cell cycle regulation and suppressed proliferation of lung cancer cells in vitro. In addition, xenograft experiments confirmed the suppression of tumor growth in vivo, which was due to the promotion of apoptosis. In conclusion, endogenous mature miR-182 expression may have an important role in the pathogenesis of lung cancer through its interference with the target gene CTTN by epigenetic modification.

摘要

肺癌是全球癌症死亡的主要原因之一。棘皮动物微管相关蛋白样蛋白 4(cortactin)基因(CTTN)可能在肿瘤的增殖和侵袭中发挥关键作用。克隆了一种 microRNA(miR-182),并用于研究 CTTN 的表达及其对肺癌细胞系 A549 增殖和侵袭的调控作用。转染 miR-182 表达质粒后,A549 细胞中的 cortactin 蛋白和 CTTN mRNA 表达降低。细胞增殖试验表明,miR-182 表达影响细胞周期调控,并抑制肺癌细胞的体外增殖。此外,异种移植实验证实了体内肿瘤生长的抑制,这是由于促进了细胞凋亡。总之,内源性成熟 miR-182 的表达可能通过表观遗传修饰干扰靶基因 CTTN,从而在肺癌的发病机制中发挥重要作用。

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