Qi Hongguo, Lu Lianwei, Wang Lili
Department of Gynaecology and Obstetrics, The Second Children & Women's Healthcare of Jinan City, Jinan, Shandong 250022, People's Republic of China.
Department of Radiology, Weifang Binhai Economic and Technological Development Zone People's Hospital, Weifang, Shandong 261108, People's Republic of China.
Onco Targets Ther. 2020 Jul 27;13:7257-7269. doi: 10.2147/OTT.S253868. eCollection 2020.
ST7 antisense RNA 1 (ST7-AS1) is a long noncoding RNA that affects the progression of gastric cancer and laryngeal squamous cell carcinoma. Herein, ST7-AS1 expression was detected in cervical cancer tissues and cell lines. In addition, its biological roles in inducing the aggressive phenotype of cervical cancer and its associated mechanisms of action were illustrated.
ST7-AS1 expression in cervical cancer tissues and cell lines was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Malignancy was determined using Cell Counting Kit-8 assay, flow cytometry, transwell migration and invasion assays, and xenograft experiments. Bioinformatics analysis was performed to predict the interaction between ST7-AS1 and microRNA-543 (miR-543). Luciferase reporter assay, RNA immunoprecipitation assay, Western blotting, qRT-PCR, and rescue experiments were performed to further identify the interactions among ST7-AS1, miR-543, and transient receptor potential melastatin 7 (TRPM7).
ST7-AS1 was upregulated in cervical cancer tissues and cell lines. ST7-AS1 overexpression was correlated with a high International Federation of Gynecology and Obstetrics stage, frequent lymph node metastasis, deep cervical invasion, and short overall survival in patients with cervical cancer. ST7-AS1 inhibition hindered cervical cancer cell proliferation, migration, and invasion; ST7-AS1 downregulation resulted in marked cell apoptosis. Additionally, ST7-AS1 deficiency restricted cervical tumor growth in vivo. Mechanistically, ST7-AS1 functioned as competing endogenous RNA to increase TRPM7 expression by sponging miR-543. Intriguingly, rescue experiments revealed that miR-543 downregulation or TRPM7 overexpression abrogated the inhibitory actions of ST7-AS1 knockdown in the aggressive phenotype of cervical cancer cells.
The newly identified ST7-AS1/miR-543/TRPM7 axis promoted the oncogenicity of cervical cancer cells both in vitro and in vivo. Our study highlighted the importance of this novel axis in cervical cancer progression, suggesting that this pathway can serve as a promising therapeutic target for cervical cancer.
ST7反义RNA 1(ST7-AS1)是一种长链非编码RNA,影响胃癌和喉鳞状细胞癌的进展。在此,检测了宫颈癌组织和细胞系中ST7-AS1的表达。此外,阐明了其在诱导宫颈癌侵袭性表型中的生物学作用及其相关作用机制。
采用定量实时聚合酶链反应(qRT-PCR)检测宫颈癌组织和细胞系中ST7-AS1的表达。使用细胞计数试剂盒-8检测、流式细胞术、Transwell迁移和侵袭检测以及异种移植实验确定恶性程度。进行生物信息学分析以预测ST7-AS1与微小RNA-543(miR-543)之间的相互作用。进行荧光素酶报告基因检测、RNA免疫沉淀检测、蛋白质免疫印迹、qRT-PCR和挽救实验,以进一步确定ST7-AS1、miR-543和瞬时受体电位香草酸亚型7(TRPM7)之间的相互作用。
ST7-AS1在宫颈癌组织和细胞系中上调。ST7-AS1过表达与国际妇产科联盟分期高、频繁淋巴结转移、宫颈深层浸润以及宫颈癌患者总生存期短相关。ST7-AS1抑制阻碍了宫颈癌细胞的增殖、迁移和侵袭;ST7-AS1下调导致明显的细胞凋亡。此外,ST7-AS1缺陷在体内限制了宫颈肿瘤的生长。机制上,ST7-AS1作为竞争性内源RNA,通过结合miR-543增加TRPM7表达。有趣的是,挽救实验表明,miR-543下调或TRPM7过表达消除了ST7-AS1敲低对宫颈癌细胞侵袭性表型的抑制作用。
新鉴定的ST7-AS1/miR-543/TRPM7轴在体外和体内均促进了宫颈癌细胞的致癌性。我们的研究强调了这一新型轴在宫颈癌进展中的重要性,表明该途径可作为宫颈癌有前景的治疗靶点。