Hu Rong-Hang, Zhang Zi-Teng, Wei Hai-Xiang, Ning Lu, Ai Jiang-Shan, Li Wen-Hui, Zhang Heng, Wang Shao-Qiang
Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, No. 89, GuHuai Road, Jining, 272029, Shandong, People's Republic of China.
Medical College of Qingdao University, Qingdao, 266071, People's Republic of China.
Cancer Cell Int. 2020 Dec 17;20(1):568. doi: 10.1186/s12935-020-01652-7.
Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD).
The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models.
ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis.
ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD.
越来越多的证据表明，致瘤性7反义RNA1（ST7-AS1）是一种致癌长链非编码RNA（lncRNA）。然而，关于其在肺腺癌（LUAD）中的临床意义、生物学功能或分子机制知之甚少。
采用qRT-PCR检测ST7-AS1和miR-181b-5p的表达。分析ST7-AS1水平与不同临床病理特征之间的相关性。在体外，分别通过MTT、伤口愈合和Transwell实验检测LUAD细胞的活力、迁移和侵袭能力。通过蛋白质免疫印迹法检测上皮-间质转化（EMT）生物标志物。通过荧光素酶报告基因实验、RNA免疫沉淀、RNA下拉实验检测ST7-AS1、miR-181b-5p和核转运蛋白α4（KPNA4）之间的调控关系。采用功能获得和功能缺失策略评估不同信号分子在LUAD细胞恶性表型中的重要性。利用异种移植和实验性转移小鼠模型分析体内效应。
ST7-AS1在LUAD组织或细胞系中上调，与阳性淋巴结转移或更高TNM分期的肿瘤相关，并与LUAD患者较短的总生存期相关。ST7-AS1基本上维持了LUAD细胞的活力、迁移、侵袭和EMT。ST7-AS1的致癌活性是通过吸附miR-181b-5p并解除后者对KPNA4的抑制来实现的。在LUAD组织中，ST7-AS1水平与KPNA4水平呈正相关，与miR-181b-5p水平呈负相关。在体内，靶向ST7-AS1显著抑制异种移植瘤的生长和转移。
ST7-AS1通过调节miR-181b-5p/KPNA4轴促进LUAD细胞的恶性程度。因此，靶向ST7-AS1和KPNA4或上调miR-181b-5p可能对LUAD的治疗有益。
