Department of Breast Surgery, Jilin Tumor Hospital, Jilin, 130012, PR China.
Department of Thoracic Neoplasms, Jilin Tumor Hospital, Jilin, 130012, PR China.
Pathol Res Pract. 2020 Feb;216(2):152772. doi: 10.1016/j.prp.2019.152772. Epub 2019 Nov 28.
Long noncoding RNA (lncRNA) GAS6-AS2 serves as an oncogenic lncRNA in various types of human cancer. In this study, we attempted to examine the functions of GAS6-AS2 in breast cancer (BC) and explore the potential mechanisms involved. Reverse-transcription quantitative PCR was carried out to determine GAS6-AS2 expression in BC tissues and cell lines. Multiple functional experiments, including a Cell Counting Kit-8 assay, Transwell migration and invasion assays, and an in vivo nude-mouse xenograft experiment, were conducted to evaluate the effects of GAS6-AS2 in BC cells. GAS6-AS2 expression was high in BC tumors, manifesting a strong correlation with tumor size, lymph node metastasis, TNM stage, and shorter overall survival in patients with BC. A knockdown of GAS6-AS2 restricted BC cell proliferation, migration, and invasion in vitro and retarded tumor growth in vivo. With regard to its mechanism, GAS6-AS2 acted as a competing endogenous RNA that sponged microRNA-493 (miR-493), thereby increasing the expression of fucosyltransferase IV (FUT4). Either miR-493 inhibition or FUT4 upregulation abrogated the consequences of GAS6-AS2 knockdown in BC cells. These results revealed that GAS6-AS2 sponges miR-493 to enhance the malignant characteristics of BC in vitro and in vivo by increasing FUT4 expression. Thus, this lncRNA is an effective therapeutic target in BC and a promising diagnostic biomarker of this cancer.
长链非编码 RNA (lncRNA) GAS6-AS2 在多种人类癌症中作为致癌 lncRNA 发挥作用。在这项研究中，我们试图研究 GAS6-AS2 在乳腺癌 (BC) 中的功能，并探讨其潜在的作用机制。采用逆转录定量 PCR 法检测 BC 组织和细胞系中 GAS6-AS2 的表达。进行了多种功能实验，包括细胞计数试剂盒-8 检测、Transwell 迁移和侵袭实验以及体内裸鼠异种移植实验，以评估 GAS6-AS2 在 BC 细胞中的作用。GAS6-AS2 在 BC 肿瘤中表达较高，与肿瘤大小、淋巴结转移、TNM 分期以及 BC 患者的总生存期较短呈强相关。敲低 GAS6-AS2 可限制 BC 细胞的增殖、迁移和侵袭，并在体内抑制肿瘤生长。关于其机制，GAS6-AS2 作为竞争性内源性 RNA，可吸附 microRNA-493 (miR-493)，从而增加岩藻糖基转移酶 IV (FUT4)的表达。抑制 miR-493 或上调 FUT4 均可消除 GAS6-AS2 敲低对 BC 细胞的影响。这些结果表明，GAS6-AS2 通过吸附 miR-493 来增强 FUT4 的表达，从而在体外和体内增强 BC 的恶性特征。因此，这种 lncRNA 是 BC 有效的治疗靶点，也是这种癌症有前途的诊断生物标志物。
