Background: 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