He Mei, Xue Yan
Department of Respiratory Medicine, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, People's Republic of China.
Onco Targets Ther. 2017 Mar 2;10:1353-1361. doi: 10.2147/OTT.S123518. eCollection 2017.
Lung cancer has the highest morbidity and mortality in the world, and non-small cell lung carcinomas (NSCLC) account for 80% of cases of lung cancer. The mechanism of NSCLC is still largely unknown, and finding novel targets is of great importance for the treatment of NSCLC. The current study was designed to evaluate the role of miR-148a in NSCLC cell proliferation and invasion and to investigate the possible molecular mechanisms. We found that miR-148a expression was decreased in NSCLC tissues and cell lines. Upregulation of miR-148a significantly decreased A549 cell proliferation, and downregulation of miR-148a significantly increased A549 cell proliferation. Upregulation of miR-148a markedly increased apoptotic cell death and inhibited cell invasion potential. Upregulation of miR-148a significantly decreased signal transducer and activator of transcription 3 (STAT3) expression and 3'-untranslated region luciferase activity. Downregulation of miR-148a significantly increased STAT3 expression. Overexpression of STAT3 significantly inhibited the effect of miR-148a on cell viability and invasion potential. In conclusion, we found that miR-148a inhibited NSCLC cell proliferation and invasion potential through the inhibition of STAT3. Our findings highlight miR-148a/STAT3 axis as a novel therapeutic target for the inhibition of NSCLC growth.
肺癌在全球具有最高的发病率和死亡率,其中非小细胞肺癌(NSCLC)占肺癌病例的80%。NSCLC的发病机制仍很大程度上未知,寻找新的靶点对于NSCLC的治疗至关重要。本研究旨在评估miR-148a在NSCLC细胞增殖和侵袭中的作用,并探讨其可能的分子机制。我们发现miR-148a在NSCLC组织和细胞系中的表达降低。上调miR-148a显著降低A549细胞增殖,而下调miR-148a则显著增加A549细胞增殖。上调miR-148a显著增加凋亡细胞死亡并抑制细胞侵袭潜能。上调miR-148a显著降低信号转导和转录激活因子3(STAT3)的表达以及3'-非翻译区荧光素酶活性。下调miR-148a显著增加STAT3表达。STAT3的过表达显著抑制miR-148a对细胞活力和侵袭潜能的影响。总之,我们发现miR-148a通过抑制STAT3来抑制NSCLC细胞增殖和侵袭潜能。我们的研究结果突出了miR-148a/STAT3轴作为抑制NSCLC生长的新治疗靶点。