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

• Published in: Cancer communications (London, England) Vol. 41; no. 3; pp. 240 - 257
• Main Authors: Zhang, Hongyue, Wang, Yan, Zhang, Weimin, Wu, Qingnan, Fan, Jiawen, Zhan, Qimin
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2021; John Wiley and Sons Inc; Wiley
• Subjects: Adaptor Proteins, Signal Transducing; BAALC‐AS1; Binding sites; Cell growth; Cell Line, Tumor; Cell Proliferation - genetics; Cyclin-dependent kinases; c‐Myc; Dehydrogenases; Efficiency; Esophageal cancer; Esophageal Neoplasms - genetics; esophageal squamous cell carcinoma; Esophageal Squamous Cell Carcinoma - genetics; Feedback; G3BP2; Gene expression; Gene Expression Regulation, Neoplastic; Genomes; Humans; Hybridization; invasion; Kinases; lncFZD6; long non‐coding RNA; Mass spectrometry; Medical diagnosis; Medical prognosis; Metastasis; MicroRNAs; migration; Neoplasm Proteins; Original; proliferation; Proteins; RNA-Binding Proteins - genetics; Scientific imaging; Squamous cell carcinoma; United States > US; China; BAALC-AS1; esophageal squamous cell carcinoma; invasion; proliferation; c-Myc; G3BP2; migration; long non-coding RNA; lncFZD6
• ISSN: 2523-3548; 2523-3548
• DOI: 10.1002/cac2.12127

Background 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). Methods 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. Results 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. Conclusions 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.