Lung cancer is one of the most common malignant diseases globally, composed of non-small cell lung cancer (NSCLC, 85%) and small cell lung cancer (SCLC, 15%). MicroRNAs (miRNAs) are single-stranded noncoding RNAs having important roles in lung cancer development. miR-411-5p/3p were reported to be increased significantly in human NSCLC tissues and cell lines. Moreover, miR-411-5p/3p overexpression could accelerate cell proliferation and migration, and impede cell apoptosis in NSCLC cell lines. Mechanically, SPRY4 is confirmed a direct target of miR-411-5p/3p. Furthermore, our findings showed that miR-411-5p/3p promoted lung tumor growth in vivo, decreased SPRY4 expression dramatically, and induced EGFR, AKT signaling activation, as well as epithelial-mesenchymal transition (EMT) simultaneously in tumor tissues. In addition, we showed that miR-411-5p also targeted tumor suppressor TXNIP, involved in regulating positively cell cycle progress in SPC-A1 cells rather than in H1299. Whether cell specificity of low TXNIP mRNA level in H1299 is responsible for the different response to cell cycle between H1299 and SPC-A1 would need further explorations. Collectively, these results suggest that miR-411-5p/3p are required for NSCLC development by suppressing SPRY4 and TXNIP; thus, the miR-411-SPRY4-AKT axis might act as a promising target for lung cancer therapy clinically.

中文翻译：

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致癌性microRNA-411通过直接靶向抑制基因SPRY4和TXNIP促进肺癌发生。

肺癌是全球最常见的恶性疾病之一，由非小细胞肺癌（NSCLC，85％）和小细胞肺癌（SCLC，15％）组成。微小RNA（miRNA）是单链非编码RNA，在肺癌的发展中具有重要作用。据报道，在人类NSCLC组织和细胞系中，miR-411-5p / 3p显着增加。而且，miR-411-5p / 3p的过表达可以促进细胞增殖和迁移，并阻止NSCLC细胞系中的细胞凋亡。在机械上，SPRY4被确认为miR-411-5p / 3p的直接靶标。此外，我们的研究结果表明，miR-411-5p / 3p在体内促进肺肿瘤生长，显着降低SPRY4表达，并在肿瘤组织中同时诱导EGFR，AKT信号激活以及上皮-间质转化（EMT）。此外，我们发现miR-411-5p还靶向肿瘤抑制因子TXNIP，参与调节SPC-A1细胞而不是H1299的细胞周期进程。H1299中低TXNIP mRNA水平的细胞特异性是否可导致H1299与SPC-A1对细胞周期的不同响应，这还需要进一步探索。总体而言，这些结果表明，通过抑制SPRY4和TXNIP，NSCLC发育需要miR-411-5p / 3p。因此，miR-411-SPRY4-AKT轴可能成为临床上有希望的肺癌治疗靶标。总体而言，这些结果表明，通过抑制SPRY4和TXNIP，NSCLC发育需要miR-411-5p / 3p。因此，miR-411-SPRY4-AKT轴可能成为临床上有希望的肺癌治疗靶标。总体而言，这些结果表明，通过抑制SPRY4和TXNIP，NSCLC发育需要miR-411-5p / 3p。因此，miR-411-SPRY4-AKT轴可能成为临床上有希望的肺癌治疗靶标。