Li Liping, Ye Dan, Liu Liang, Li Xiaoju, Liu Jun, Su Shengtian, Lu Wenjing, Yu Zhigao
Department of Oncology, Xiantao First People's Hospital, Xiantao, Hubei, People's Republic of China.
Cancer Manag Res. 2020 Sep 10;12:8303-8312. doi: 10.2147/CMAR.S258487. eCollection 2020.
Non-small cell lung cancer (NSCLC) is a typical epithelial lung cancer with high metastasis, incidence and mortality. In recent years, long noncoding RNA small nucleolar RNA host gene 7 () has been identified as significant regulator in different cancer types, including NSCLC. However, the underlying molecular mechanism of during NSCLC tumorigenesis and progression remains largely unclear.
and miR-181a-5p expression in NSCLC tumors and cells were detected by qRT-PCR. Cell viability, migration, invasion and apoptosis were evaluated by CCK-8, transwell and flow cytometry assay, respectively. A549 and NCI-H1299 xenograft mice model was constructed by subcutaneously injecting cells stably transfected with sh-SNHG7 and sh-NC. The interaction between and miR-181a-5p was validated by luciferase reporter system, RIP and RNA pull down assay. Protein expression of cleaved caspase 3, proliferating cell nuclear antigen (PCNA), AKT, p-AKT, mammalian target of rapamycin (mTOR) and p-mTOR was analyzed by Western blot.
expression was up-regulated while miR-181a-5p expression was down-regulated in NSCLC tumors, especially those from patients at Phase III+IV, compared with normal tissues. However, depletion attenuated tumor growth in vitro and in vivo. Moreover, miR-181a-5p inhibitor abolished silencing induced inhibition on proliferation, migration and invasion in NSCLC. Subsequently, we found modulated cell progression by targeting miR-181a-5p and activating AKT/mTOR signaling pathway.
SNHG7 accelerates proliferation, migration and invasion of NSCLC by suppressing miR-181a-5p through AKT/mTOR signaling pathway, thus presenting desirable biomarkers for NSCLC therapy.
非小细胞肺癌（NSCLC）是一种具有高转移率、发病率和死亡率的典型上皮性肺癌。近年来，长链非编码RNA小核仁RNA宿主基因7（SNHG7）已被确定为包括NSCLC在内的不同癌症类型中的重要调节因子。然而，SNHG7在NSCLC肿瘤发生和进展过程中的潜在分子机制仍不清楚。
采用qRT-PCR检测NSCLC肿瘤组织和细胞中SNHG7和miR-181a-5p的表达。分别通过CCK-8、Transwell和流式细胞术检测细胞活力、迁移、侵袭和凋亡。通过皮下注射稳定转染sh-SNHG7和sh-NC的细胞构建A549和NCI-H1299异种移植小鼠模型。通过荧光素酶报告系统、RIP和RNA下拉实验验证SNHG7与miR-181a-5p之间的相互作用。通过蛋白质免疫印迹分析裂解的半胱天冬酶3、增殖细胞核抗原（PCNA）、AKT、p-AKT、雷帕霉素靶蛋白（mTOR）和p-mTOR的蛋白表达。
与正常组织相比，NSCLC肿瘤组织中SNHG7表达上调，而miR-181a-5p表达下调，尤其是III+IV期患者的肿瘤组织。然而，SNHG7缺失可减弱体外和体内肿瘤生长。此外，miR-181a-5p抑制剂消除了SNHG7沉默诱导的对NSCLC增殖、迁移和侵袭的抑制作用。随后，我们发现SNHG7通过靶向miR-181a-5p并激活AKT/mTOR信号通路来调节细胞进程。
SNHG7通过AKT/mTOR信号通路抑制miR-181a-5p，从而加速NSCLC的增殖、迁移和侵袭，因此有望成为NSCLC治疗的生物标志物。
