Xue Xinying, Liu Yuxia, Wang Yong, Meng Mingming, Wang Kaifei, Zang Xuefeng, Zhao Sheng, Sun Xiaohua, Cui Lei, Pan Lei, Liu Sanhong
Department of Special Medical Treatment-Respiratory Disease, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Department of Respiratory Diseases of Chinese PLA General Hospital, Beijing, China.
Oncotarget. 2016 Dec 20;7(51):84508-84519. doi: 10.18632/oncotarget.13022.
Lung cancer remains the leading cause of cancer-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and whether these miRNAs share common targets, such as tumor suppressor genes required to prevent NSCLC. Here we report that miR-21 and miR-155 levels are elevated in NSCLC and are proportional to the progression of the disease. In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1, SOCS6, and PTEN, three tumor suppressor genes often silenced in NSCLC. Consequently, antagonizing miR-21, miR-155 or both potently inhibited tumor progression in xenografted animal models of NSCLC. Treatment with miR-21 and miR-155 inhibitors in combination was always more effective against NSCLC than treatment with a single inhibitor. Furthermore, levels of miR-21 and miR-155 expression correlated inversely with overall and disease-free survival of NSCLC patients. Our findings reveal that miR-21 and miR-155 promote the development of NSCLC, in part by downregulating SOCS1, SOCS6, and PTEN. Combined inhibition of miR-21 and miR-155 could improve the treatment of NSCLC.
肺癌仍是全球癌症相关死亡的主要原因。MiR-21和miR-155是非小细胞肺癌（NSCLC）中扩增最为明显的微小RNA，是NSCLC进展的关键促进因子。然而，目前尚不清楚miR-21和miR-155如何诱导癌症进展，以及这些微小RNA是否共享共同的靶点，如预防NSCLC所需的肿瘤抑制基因。在此，我们报告miR-21和miR-155水平在NSCLC中升高，且与疾病进展成正比。此外，miR-21和miR-155有近30%的预测靶基因相同，包括SOCS1、SOCS6和PTEN，这三个肿瘤抑制基因在NSCLC中常被沉默。因此，拮抗miR-21、miR-155或两者均拮抗可有效抑制NSCLC异种移植动物模型中的肿瘤进展。联合使用miR-21和miR-155抑制剂治疗NSCLC总是比单独使用一种抑制剂更有效。此外，miR-21和miR-155的表达水平与NSCLC患者的总生存期和无病生存期呈负相关。我们的研究结果表明，miR-21和miR-155部分通过下调SOCS1、SOCS6和PTEN促进NSCLC的发展。联合抑制miR-21和miR-155可改善NSCLC的治疗效果。
