目的：探究miR-625 和Resistin 对NSCLC细胞增殖、侵袭、迁移及裸鼠移植瘤生长的影响及其可能的机制。方法：qPCR 实验检测80 例NSCLC 及癌旁组织（标本收集自2018 年3 月至2019 年10 月于新疆维吾尔自治区人民医院手术治疗的NSCLC患者）和4 种细胞系中miR-625 与Resistin 的表达，生物信息学预测两者的靶向关系并用双荧光素酶基因报告实验进行验证；通过脂质体转染技术在NSCLC细胞中过表达或抑制miR-625 及Resistin 表达，实验分为miR-625 mimic 组、miR-625 inhibitor组、si-Resisitin 组、miR-625 inhibitor+si-Resisitin 组和NC组，利用CCK-8、Transwell 及划痕实验检测miR-625 与Resistin 对NSCLC细胞增殖、侵袭及迁移的影响，Western blotting 实验检测两者对NSCLC细胞中EMT相关的PI3K/AKT/Snail 通路蛋白表达的影响，裸鼠成瘤实验观察两者对A549 细胞移植瘤生长的影响。结果：miR-625 在NSCLC组织和4 种细胞系中呈低表达、Resistin呈高表达（均P<0.01），两者表达水平呈负相关（r=-0.7183，P<0.01），且Resistin 的表达与NSCLC分化程度、临床分期及淋巴结转移相关。Resistin 是miR-625 的靶基因。在NSCLC 细胞系A549 和H226 的增殖、侵袭、迁移能力及裸鼠移植瘤的生长方面，与Blank 组和NC组相比，miR-625 mimic 组与si-Resistin 组能力均显著降低（均P<0.05），miR-625 inhibitor 组显著提高（均P<0.05）；miR-625 inhibitor+si-Resistin 组显著低于miR-625 inhibitor 组（均P<0.05）；NC组与miR-625 inhibitor+si-Resistin 组之间无显著差异（均P>0.05）；p-AKT、p-PI3K、Snail、Twist1、Vimentin 等蛋白表达变化也有相同的趋势（均P<0.05），E-cadherin 蛋白表达则发生相反的改变（P<0.05）。结论：miR-625 在NSCLC组织和细胞中均呈低表达，其能负向调控Resistin 表达从而抑制NSCLC细胞的增殖、侵袭和迁移及裸鼠移植瘤生长，其机制可能与PI3K/AKT/Snail信号通路有关。

Objective: To investigate the effects of miR-625 and Resistin on the proliferation, invasion and migration of NSCLC cells as well as the growth of transplanted tumors in nude mice and their possible mechanisms. Methods: qPCR was used to detect the expression of miR-625 and Resistin in 80 pairs of NSCLC and corresponding para-cancerous tissues (specimens collected from NSCLC patients who were surgically treated in Xinjiang Uygur Autonomous Region People’s Hospital from March 2018 to October 2019) and four cell lines. Bioinformatics was adopted to predict the targeting relationship between miR-625 and Resistin, which was then verified by Dual luciferase gene reporter experiment. Overexpression or inhibition of miR-625 and Resistin in NSCLC cells was achieved with lipofection transfection technology, and the experimental cells were divided into miR-625 mimic group, miR-625 inhibitor group, si-Resisitin group, miR-625 inhibitor+si-Resisitin group and NC group. The effects of miR-625 and Resistin on proliferation, invasion and migration of NSCLC cells were detected by CCK-8, Transwell and Scratch test, respectively. Western blotting was used to detect the effects of miR-625 and Resistin on the expressions of PI3K/AKT/Snail pathway proteins related with EMT in NSCLC cells. A549 cell transplanted tumor model was constructed in nude mice to observe the effect of miR-625 and Resistin on the growth of xenografts. Results: Compared with para-cancerous tissues, miR-625 showed low expression while Resistin showed high expression in NSCLC tissues and four cell lines (both P<0.01), and the two were negatively correlated (r=-0.7183,P<0.01). The expression of Resistin was related to the degree of NSCLC differentiation, clinical stage and lymph node metastasis. Resistin was a target gene of miR-625. Compared with the Blank group and NC group, the proliferation, invasion and migration of NSCLC cell lines A549 and H226, as well as the growth of transplanted tumors in nude mice in the miR-625 mimic group and the si-Resistin group were significantly reduced (all P<0.05), while those indicators in the miR-625 inhibitor group were significantly improved (all P<0.05); However, co-transfection of miR-625 inhibitor and si-Resistin significantly reversed the effect of miR-625 inhibitor on above indicators (all P<0.05); And there was no significant difference between NC group and miR-625 inhibitor+si-Resistin group (all P>0.05). The protein expressions of p-AKT, p-PI3K, Snail, Twist1 and Vimentin also showed the same trend (all P<0.05), while the expression of E-cadherin protein changed in the opposite direction (P<0.05). Conclusion: miR-625 is lowly expressed in NSCLC tissues and cell lines, which can negatively regulate Resistin expression to inhibit the proliferation, invasion and migration of NSCLC cells and the growth of transplanted tumors in nude mice. The mechanism may be related to the PI3K/AKT/Snail signaling pathway.

新疆维吾尔自治区自然科学基金资助项目（No. 2019D01C108）