OncoTargets and Therapy (Jul 2020)
Long Noncoding RNA ST7-AS1 Upregulates TRPM7 Expression by Sponging microRNA-543 to Promote Cervical Cancer Progression
Abstract
Hongguo Qi,1 Lianwei Lu,2 Lili Wang3 1Department of Gynaecology and Obstetrics, The Second Children & Women’s Healthcare of Jinan City, Jinan, Shandong 250022, People’s Republic of China; 2Department of Radiology, Weifang Binhai Economic and Technological Development Zone People’s Hospital, Weifang, Shandong 261108, People’s Republic of China; 3Department of Gynaecology and Obstetrics, The 5th People’s Hospital of Jinan, Jinan, Shandong 250022, People’s Republic of ChinaCorrespondence: Lili WangDepartment of Gynaecology and Obstetrics, The 5th People’s Hospital of Jinan, 24297 Jingshi Road, Jinan, Shandong 250022, People’s Republic of ChinaEmail [email protected]: 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.Patients and Methods: 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).Results: 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.Conclusion: 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.Keywords: ST7 antisense RNA 1, cervical cancer, transient receptor potential melastatin 7, microRNA-543
