Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277, Jiefang Avenue, Wuhan 430022, China.
Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20191764.
Breast cancer (BC) poses a great threaten to women health. Numerous evidences suggest the important role of long non-coding RNAs (lncRNAs) in BC development. In the present study, we intended to investigate the role of ARAP1-AS1 in BC progression. First of all, the GEPIA data suggested that ARAP1-AS1 was highly expressed in breast invasive carcinoma (BRAC) tissues compared with the normal breast tissues. Meanwhile, the expression of ARAP1-AS1 was greatly up-regulated in BC cell lines. ARAP1-AS1 knockdown led to repressed proliferation, strengthened apoptosis and blocked migration of BC cells. Moreover, ARAP1-AS1 could boost HDAC2 expression in BC through sponging miR-2110 via a ceRNA mechanism. Of note, the UCSC predicted that HDAC2 was a potential transcriptional regulator of PLIN1, an identified tumor suppressor in BC progression. Moreover, we explained that the repression of HDAC2 on PLIN1 was owing to its deacetylation on PLIN1 promoter. More importantly, depletion of PLIN1 attenuated the mitigation function of ARAP1-AS1 silence on the malignant phenotypes of BC cells. To sum up, ARAP1-AS1 serves a tumor-promoter in BC development through modulating miR-2110/HDAC2/PLIN1 axis, which may help to develop novel effective targets for BC treatment.
乳腺癌（BC）对女性健康构成了巨大威胁。大量证据表明长非编码 RNA（lncRNAs）在 BC 发展中起着重要作用。在本研究中，我们旨在研究 ARAP1-AS1 在 BC 进展中的作用。首先，GEPIA 数据表明，ARAP1-AS1 在乳腺浸润性癌（BRAC）组织中的表达明显高于正常乳腺组织。同时，ARAP1-AS1 在 BC 细胞系中的表达也显著上调。ARAP1-AS1 敲低导致 BC 细胞增殖受到抑制，凋亡增强，迁移受阻。此外，ARAP1-AS1 通过海绵吸附 miR-2110 来增强 BC 中的 HDAC2 表达，从而发挥 ceRNA 机制。值得注意的是，UCSC 预测 HDAC2 是 BC 进展中 PLIN1 的潜在转录调节因子，PLIN1 是一种已鉴定的肿瘤抑制因子。此外，我们还解释说，HDAC2 对 PLIN1 的抑制作用是由于其对 PLIN1 启动子的去乙酰化作用。更重要的是，PLIN1 的耗竭减弱了 ARAP1-AS1 沉默对 BC 细胞恶性表型的缓解作用。总之，ARAP1-AS1 通过调节 miR-2110/HDAC2/PLIN1 轴在 BC 发展中起致癌作用，这可能有助于为 BC 治疗开发新的有效靶点。
