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.

乳腺癌是女性最常见的癌症之一，在全世界范围内发病率和死亡率都很高。大量研究表明，长链非编码RNA（lncRNA）在人类癌症的发生和发展中发挥着重要作用。尽管已揭示lncRNA GAS6-AS1参与多种癌症类型的调控，但GAS6-AS1在乳腺癌中的作用和调控机制仍不清楚。在本文中，我们的研究结果表明，GAS6-AS1在乳腺癌组织和细胞系中表达显着升高，GAS6-AS1的高水平反映了乳腺癌患者的不良预后。此外，GAS6-AS1敲低可抑制细胞增殖、迁移和侵袭，并促进细胞凋亡。我们进一步发现，GAS6-AS1 的缺失通过抑制通路相关蛋白的水平来抑制 PI3K/AKT 信号通路。从机制上讲，GAS6-AS1 充当竞争性内源 RNA (ceRNA)，海绵 miR-324−3p 并上调 SETD1A 表达。此外，GAS6-AS1 通过靶向 miR-324−3p/SETD1A 轴激活 PI3K/AKT 通路。拯救试验表明，SETD1A 过表达或 740Y-P 治疗逆转了沉默的 GAS6-AS1 对乳腺癌细胞进展的抑制作用。综上所述，本工作首先探讨了GAS6-AS1在乳腺癌细胞中的分子调控机制，揭示GAS6-AS1通过miR-324−3p/SETD1A轴激活PI3K/AKT通路促进乳腺癌细胞的恶性行为。