LncRNA GAS6-AS1 facilitates the progression of breast cancer by targeting the miR-324-3p/SETD1A axis to activate the PI3K/AKT pathway.

Breast cancer is one of the most prevalent cancers in women with a high incidence and mortality worldwide. A great number of studies have indicated that long non-coding RNAs (lncRNAs) play significant roles in the initiation and development of human cancers. Although it has been revealed that lncRNA GAS6-AS1 is involved in the regulation of several cancer types, the role and regulatory mechanism of GAS6-AS1 in breast cancer remain unclear. In this paper, our findings showed that GAS6-AS1 expression was significantly elevated in breast cancer tissues and cell lines, and the high level of GAS6-AS1 reflected a poor prognosis of patients with breast cancer. Moreover, GAS6-AS1 knockdown suppressed cell proliferation, migration and invasion as well as facilitated cell apoptosis. We further found that the depletion of GAS6-AS1 suppressed the PI3K/AKT signaling pathway through inhibiting the levels of pathway-related proteins. Mechanically, GAS6-AS1 acted as a competing endogenous RNA (ceRNA) to sponge miR-324-3p and upregulate SETD1A expression. Besides, GAS6-AS1 activated the PI3K/AKT pathway by targeting the miR-324-3p/SETD1A axis. Rescue assays showed that SETD1A overexpression or 740Y-P treatment reversed the inhibitory effect of silenced GAS6-AS1 on cellular progresses of breast cancer. In summary, this work first explored the molecular regulatory mechanism of GAS6-AS1 in breast cancer cells and revealed that GAS6-AS1 facilitated the malignant behaviors of breast cancer cells by the miR-324-3p/SETD1A axis to activate the PI3K/AKT pathway.