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

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.