MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1
MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1
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DOI：
10.4161/rna.8.1.14259
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发表时间：
2011-01-01
期刊：
影响因子：
4.1
通讯作者：
Au, Joseph S. K.
中科院分区：
文献类型：
--
作者：
Cho, William C. S.;Chow, Andrew S. C.;Au, Joseph S. K.
MicroRNAs （miRNAs）作为重要的细胞通路调节剂出现，在肿瘤发生中起着关键作用。MiR-145在包括肺癌在内的几种人类恶性肿瘤中下调，但其分子机制尚不清楚。我们之前报道过，恢复hsa-miR-145可以抑制表皮生长因子受体（EGFR）突变的肺腺癌患者的癌细胞生长。本研究表明，hsa-miR-145靶向肺腺癌细胞中的EGFR和核苷二磷酸连接片段x型基序1 （NUDT1或MTH1）。转染miR-145后，人肺腺癌细胞中EGFR和NUDT1的mRNA表达显著下调。我们的研究结果表明，miR-145在mRNA和蛋白水平上负调控EGFR和NUDT1的表达。进一步分析表明，miR-145在转染的肺腺癌细胞的三个时间点（24、48和72小时）上具有抑制细胞增殖的能力。miR-145的上调似乎是肺腺癌细胞增殖的重要基因调控机制，且与EGFR和NUDT1的下调密切相关。有趣的是，我们的研究发现肺癌细胞增殖的改变并不伴随着细胞凋亡的改变。我们的研究结果为miR-145、EGFR、NUDT1和其他未知因子组成的复杂调控途径提供了新的见解，这些因子在细胞增殖中起作用，但在细胞凋亡中不起作用。了解miR-145的靶点及其调控途径可能会导致肺腺癌的新治疗策略。
MicroRNAs (miRNAs) are emerging as important modulators in cellular pathways and they appear to play a key role in tumorigenesis. MiR-145 is downregulated in several human malignancies, including lung cancer, but the responsible molecular mechanisms remain unclear. We previously reported that restoration of hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. This study showed that hsa-miR-145 targets EGFR and nucleoside diphosphate linked moiety X-type motif 1 (NUDT1 or MTH1) in lung adenocarinoma cells. The mRNA expressions of EGFR and NUDT1 were significantly downregulated after miR-145 transfection in human lung adenocarcinoma cells. Our results demonstrated miR-145 in the negative regulation of EGFR and NUDT1 expressions at both mRNA and protein levels. Further analysis showed that miR-145 has the ability to inhibit cell proliferation on transfected lung adenocarcinoma cells over three time points (24, 48 and 72 hours). Upregulation of miR-145 appeared to be an important gene regulation mechanism for the proliferation of lung adenocarcinoma cells and it correlated strongly with the downregulation of EGFR and NUDT1. Interestingly, our study revealed that the altered proliferation in lung cancer cells is not accompanied by changes in apoptosis. Our findings provided new insight into the complex regulating pathway comprising of miR-145, EGFR, NUDT1 and other unknown factors which function in cell proliferation but not in apoptosis. Understanding miR-145's targets and its regulating pathways may lead to new therapeutic strategies for lung adenocarcinoma.