BAALC-AS1/G3BP2/c-Myc feedback loop promotes cell proliferation in esophageal squamous cell carcinoma.

BAALC-AS1/G3BP2/c-Myc feedback loop promotes cell proliferation in esophageal squamous cell carcinoma.
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BAALC-AS 1/G3 BP 2/c-Myc反馈环促进食管鳞癌细胞增殖

DOI:
10.1002/cac2.12127
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发表时间:
2021-03
期刊:
Cancer communications (London, England)
影响因子:
--
通讯作者:
Zhan Q
Zhan Q
中科院分区:
其他
文献类型:
--
作者:
Zhang H;Wang Y;Zhang W;Wu Q;Fan J;Zhan Q

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已发现长链非编码RNA(lncRNA)参与许多癌症的发展。本研究旨在探讨lncRNA BAALC反义RNA 1(BAALC‐ AS 1)调控食管鳞状细胞癌(ESCC)恶性程度的分子机制。使用组织微阵列分析癌症患者中BAALC-AS 1的表达。分别通过Western印迹分析和定量逆转录-PCR(RT-qPCR)测定BAALC-AS 1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下拉试验和荧光素酶试验确定BAALC-AS 1、RasGAPSH 3结构域结合蛋白2(G3 BP 2)和c-Myc之间的关系。BAALC-AS 1的表达高度上调,并与ESCC组织和细胞系的恶性表型相关。体内和体外实验表明,BAALC-AS 1促进ESCC细胞增殖、迁移和侵袭。BAALC-AS 1直接与G3 BP 2相互作用,从而抑制G3 BP 2对c-Myc RNA 3 '-UTR的降解,从而导致c-Myc表达的积累。此外,c-Myc作为转录因子,可以通过直接结合其启动子区域诱导BAALC-AS 1的表达。BAALC-AS 1/G3 BP 2/c-Myc反馈环在ESCC的发生发展中起着关键作用,可能为ESCC的治疗提供新的靶点,并促进新的治疗策略的开发。
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.
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