She Kelin, Yan Hui, Huang Jun, Zhou Huaping, He Jianxing
Southern Medical University, Guangzhou, China.
Department of Thoracic Surgery, the Central Hospital of Shaoyang City, Shaoyang, Hunan Province, China.
Cell Prolif. 2018 Feb;51(1). doi: 10.1111/cpr.12406. Epub 2017 Nov 12.
Long non-coding RNAs have identified to involve into the tumour cell proliferation, apoptosis and metastasis. We previously found that up-regulated LncRNA-SNHG7 (SNHG7) positively correlated to the Fas apoptosis inhibitory molecule 2 (FAIM2) in lung cancer cells with unclear mechanism.
Non-small cell lung cancer (NSCLC) and relative normal tissues (n = 25) were collected. The SNHG7 expression and function in NSCLC was determined. The SNHG7-miR 193b-FAIM2 network was analysed in vitro and vivo.
We reported that oncogene SNHG7 predicted a poor clinical outcome and functioned as competitive endogenous RNA (ceRNA) antagonized microRNA-193b (miR-193b) to up-regulate the FAIM2 level in NSCLC. Bioinformatic analysis predicted that SNHG7 harboured miR-193b-binding sites, and we found decreased miR-193b levels in NSCLC tissues when compared to relative normal tissues. Luciferase assays indicated that overexpression of miR-193b inhibited the Ruc expression of plasmid with miR-193b-binding sites of SNHG7 in a dose-dependent manner. Ectopically expressed SNHG7 also as a molecular sponge sequestered endogenous miR-193b. Besides, FAIM2 was found to be directly targeted by miR-193b. The restoration of miR-193b levels in NSCLC cell lines A549 and H125 suppressed the expression of FAIM2 and related tumour proliferation, metastasis and induced apoptosis. However, forced expression of SNHG7 could down-regulate miR-193b to elevate the FAIM2 level of tumour cells, leading to impaired miR-193b/FAIM2-induced tumour progression. Knockdown of SNHG7 in vivo significantly delayed the tumour growth with decreased tumour volume, which accompanied with enhanced miR-193b expression and reduced FAIM2 levels.
The results indicated that miR-193b is indispensible for the ceRNA role of SNHG7 in FAIM2-supported tumourigenesis of lung cancer.
长链非编码RNA已被证实参与肿瘤细胞增殖、凋亡及转移过程。我们之前发现，在肺癌细胞中上调的LncRNA-SNHG7（SNHG7）与Fas凋亡抑制分子2（FAIM2）呈正相关，但其机制尚不清楚。
收集25例非小细胞肺癌（NSCLC）组织及相对应的正常组织。检测SNHG7在NSCLC中的表达及功能。在体内外分析SNHG7-miR 193b-FAIM2网络。
我们报道癌基因SNHG7预示着不良临床预后，且作为竞争性内源性RNA（ceRNA）发挥作用，拮抗微小RNA-193b（miR-193b），从而上调NSCLC中FAIM2的水平。生物信息学分析预测SNHG7含有miR-193b结合位点，且我们发现与相对正常组织相比，NSCLC组织中miR-193b水平降低。荧光素酶检测表明，miR-193b的过表达以剂量依赖的方式抑制了含有SNHG7的miR-193b结合位点的质粒的荧光素酶表达。异位表达的SNHG7也作为分子海绵隔离内源性miR-193b。此外，发现FAIM2是miR-193b的直接靶点。NSCLC细胞系A549和H125中miR-193b水平的恢复抑制了FAIM2的表达以及相关肿瘤增殖、转移并诱导凋亡。然而，SNHG7的强制表达可下调miR-193b，从而提高肿瘤细胞中FAIM2的水平，导致miR-193b/FAIM2诱导的肿瘤进展受损。体内敲低SNHG7显著延迟肿瘤生长，肿瘤体积减小，同时miR-193b表达增强，FAIM2水平降低。
结果表明，miR-193b对于SNHG7在FAIM2支持的肺癌肿瘤发生中的ceRNA作用不可或缺。
