OncoTargets and Therapy (May 2020)
LncRNA TTN-AS1 Regulates miR-524-5p and RRM2 to Promote Breast Cancer Progression
Abstract
Hui Feng, Qi Wang, Wenjing Xiao, Biyuan Zhang, Yonglong Jin, Haijun Lu Department of Radiotherapy, Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, People’s Republic of ChinaCorrespondence: Haijun LuDepartment of Radiotherapy, Affiliated Hospital of Qingdao University, Jiangsu Road No. 16, Shinan District, Qingdao 266000, Shandong, People’s Republic of ChinaTel +8618661809125Email [email protected]: Recent studies suggest many long non-coding RNAs (lncRNAs) are crucial oncogenes or tumor suppressors. This study intended to investigate the biological function and mechanism of lncRNA TTN antisense RNA 1 (TTN-AS1) in the progression of breast cancer (BC).Materials and Methods: BC tissue samples were collected. The expression of TTN-AS1 in BC tissues and adjacent tissues was detected by qRT-PCR, and the relationship between pathological indicators and TTN-AS1 expression was analyzed by chi-square test. BC cell lines T47D and BT549 were utilized as cell models. CCK-8 assay and BrdU assay were used to detect the effect of TTN-AS1 on BC cell proliferation. Transwell assay was used to detect the effects of TTN-AS1 on cell migration and invasion. In addition, dual-luciferase reporter gene assay was used to confirm the targeting relationship between miR-524-5p and TTN-AS1. Western blot was used to detect the function of TTN-AS1 on regulating ribonucleotide reductase subunit 2 (RRM2) and survivin. Additionally, subcutaneous xenotransplanted tumor model and tail vein injection model were constructed in vivo.Results: The expression of TTN-AS1 in BC tissues was significantly higher than that in normal tissues, and its high expression was correlated with adverse pathological indicators. Overexpression of TTN-AS1 significantly promoted the proliferation, migration and invasion of BC cells. TTN-AS1 knockdown suppressed the malignant phenotypes of BC cells. TTN-AS1 overexpression significantly impeded the expression of miR-524-5p, but increased the expression of RRM2.Conclusion: TTN-AS1 exerts oncogenic function in BC by repressing miR-524-5p and increasing the expression of RRM2.Keywords: breast cancer, lncRNA, TTN-AS1, miR-524-5p, RRM2
