Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, P. R. China.
Shenzhen Bay Laboratory, Shenzhen, Guangdong, 518132, P. R. China.
Cancer Commun (Lond). 2021 Mar;41(3):240-257. doi: 10.1002/cac2.12127. Epub 2021 Jan 21.
Long non-coding RNAs (lncRNAs) have been found to be involved in the development of many cancers. In this study, we aimed to identify the molecular mechanisms of lncRNA BAALC antisense RNA 1 (BAALC-AS1) in regulating the malignancy of esophageal squamous cell carcinoma (ESCC).
The expression of BAALC-AS1 in cancer patients was analyzed using a tissue microarray. The protein and RNA levels of BAALC-AS1 were determined by Western blotting analysis and quantitative reverse transcription-PCR (RT-qPCR), respectively. The cell proliferation was determined by cell viability assays, bromodeoxyuridine incorporation, and flow cytometry. The relationships among BAALC-AS1, RasGAPSH3 domain-binding protein 2 (G3BP2), and c-Myc were determined using RNA immunoprecipitation, RNA pull-down assays, and luciferase assays.
The expression of BAALC-AS1 was highly up-regulated and associated with malignant phenotypes in ESCC tissues and cell lines. In vivo and in vitro assays showed that BAALC-AS1 promoted ESCC cell proliferation, migration, and invasion. BAALC-AS1 directly interacted with G3BP2, and thereby inhibited the degradation of c-Myc RNA 3'-UTR by G3BP2, thus leading to the accumulation of c-Myc expression. Additionally, c-Myc acted as a transcription factor that can induce the expression of BAALC-AS1 by directly binding to its promoter region.
BAALC-AS1/G3BP2/c-Myc feedback loop plays a critical role in the development of ESCC, which might provide a novel therapeutic target and facilitate the development of new therapeutic strategies for the treatment of ESCC.
长链非编码 RNA（lncRNA）已被发现参与多种癌症的发生。本研究旨在鉴定 lncRNA BAALC 反义 RNA 1（BAALC-AS1）在调节食管鳞状细胞癌（ESCC）恶性程度中的分子机制。
使用组织微阵列分析癌症患者中 BAALC-AS1 的表达。通过 Western blot 分析和定量逆转录聚合酶链反应（RT-qPCR）分别测定 BAALC-AS1 的蛋白和 RNA 水平。通过细胞活力测定、溴脱氧尿苷掺入和流式细胞术测定细胞增殖。使用 RNA 免疫沉淀、RNA 下拉测定和荧光素酶测定确定 BAALC-AS1、RasGAPSH3 结构域结合蛋白 2（G3BP2）和 c-Myc 之间的关系。
BAALC-AS1 的表达在 ESCC 组织和细胞系中高度上调，并与恶性表型相关。体内和体外实验表明，BAALC-AS1 促进 ESCC 细胞增殖、迁移和侵袭。BAALC-AS1 与 G3BP2 直接相互作用，从而抑制 G3BP2 对 c-Myc RNA 3'-UTR 的降解，导致 c-Myc 表达的积累。此外，c-Myc 作为转录因子，可通过直接结合其启动子区域诱导 BAALC-AS1 的表达。
BAALC-AS1/G3BP2/c-Myc 反馈环在 ESCC 的发生发展中起着关键作用，这可能为 ESCC 的治疗提供新的治疗靶点，并有助于开发新的治疗策略。
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