Conclusion
The newly identified TTC39A-AS1/miR-483-3p/MTA2 pathway was revealed to be a critical regulator in the tumorigenicity of BC, possibly offering a novel therapeutic direction for the anticancer treatment of BC.
Methods
Quantitative RT-PCR was performed to determine the expression levels of TTC39A-AS1, microRNA-483-3p (miR-483-3p), and metastasis-associated gene 2 (MTA2). Further, the detailed functions of TTC39A-AS1 in BC cells were confirmed using the Cell Counting Kit 8 assay, flow cytometric analysis, and Transwell cell migration and invasion assays. The targeting relationship between TTC39A-AS1, miR-483-3p, and MTA2 in BC was predicted via bioinformatics analysis and further confirmed by performing the luciferase reporter assay and RNA immunoprecipitation.
Results
TTC39A-AS1 was present in high levels in BC; this result was confirmed in our sample cohort and The Cancer Genome Atlas database. Patients with BC with a high level of TTC39A-AS1 had a shorter overall survival than those with a low level of TTC39A-AS1. Functionally, the absence of TTC39A-AS1 accelerated cell apo-ptosis but retained cell proliferation, migration, and invasion. Mechanistically, TTC39A-AS1 functioned as a competing endogenous RNA in BC by sponging miR-483-3p and thereby indirectly increasing MTA2 expression. Finally, rescue experiments revealed that the tumor-inhibiting actions of TTC39A-AS1 knockdown on the malignant characteristics of BC cells could be reversed by inhibiting miR-483-3p or upregulating MTA2.