Triple-negative breast cancer (TNBC) is an aggressive
cancer, and rapidly progresses following relapse in advanced stage. This
cancer is usually associated with worse overall survival, so the
carcinogenesis of TNBC needs to be further explored to find more effective
therapies. In this study, we intended to identify the roles of YY1-mediated
long non-coding RNA Kcnq1ot1 in TNBC. First, the paired samples of
tumor tissues and adjacent tissues were collected to determine YY1,
lncRNA Kcnq1ot1, and PTEN expression using RT-qPCR and Western blot analysis followed by analysis of the relationship between them and patient survival. The results revealed that YY1 and
lncRNA Kcnq1ot1 were upregulated in TNBC tissues, and high expression of YY1 and
lncRNA Kcnq1ot1 was associated with poor patient survival. Then, ChIP and MSP assays were employed to explore interactions between YY1,
lncRNA Kcnq1ot1, and PTEN gene. We obtained that YY1 upregulated
lncRNA Kcnq1ot1, which mediated PTEN methylation via DNMT1, thus decreasing PTEN expression. Afterward, TNBC cells were examined for their viability using functional assays with the results displaying that overexpression of YY1 facilitated TNBC cell proliferation, invasion, and migration. Mechanistically, upregulated YY1 repressed
tumor growth by inhibiting PTEN via upregulation of
lncRNA Kcnq1ot1. Mouse models were also constructed, and the above effects of YY1,
lncRNA Kcnq1ot1, and PTEN on TNBC were also established in vivo. Taken together, this study demonstrates that the silencing of YY1 exerted
tumor-suppressive effects on TNBC by modulating
lncRNA Kcnq1ot1/DNMT1/PTEN pathway, in support of further investigation into anti-
tumor therapy for TNBC.