RESUMO
Triple-negative breast cancer (TNBC) is a complex breast cancer subtype characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2). Long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) has been verified as oncogenic molecular in series of tumors, however, the role of ANRIL in TNBC carcinogenesis is still unclear. The purpose of present study is to investigate the expression and in-depth regulation of ANRIL on TNBC tumorigenesis. Expression level of ANRIL was up-regulated in TNBC tumor tissue and cell lines compared to noncancerous tissue and non-TNBC cells. Besides, the up-regulated ANRIL expression was closely correlated to poor prognosis. In vitro, loss-of-function experiments showed that ANRIL knockdown interfered by interference oligonucleotide could markedly suppress TNBC cells proliferation and enhance apoptosis. In vivo, ANRIL knockdown inhibited the tumor growth. Bioinformatics analysis and luciferase reporter assay revealed that miR-199a targeted ANRIL at 3'-UTR. Rescue experiments showed that miR-199a inhibitor could reverse the tumor-suppressing role of ANRIL knockdown on TNBC proliferation and apoptosis. Overall, present study demonstrated that ANRIL overexpression modulated TNBC tumorigenesis through acting as molecular 'sponge' for miR-199a, providing a novel insight and therapeutic target for TNBC.
