Approach to Functions of BHLHE41/DEC2 in Non-Small Lung Cancer Development

Abstract

The circadian rhythm-related genes BHLHE40/DEC1 and BHLHE41/DEC2 have various functions under different cell and tissue conditions. BHLHE41/DEC2 has been reported to be both a cancer-suppressive and an oncogenic gene during cancer development. The effects of BHLHE41/DEC2 on differentiation have been examined using Bhlhe41/Dec2 knockout mice and/or in vitro differentiation models, and research has been conducted using genetic analysis of tumor cells, in vitro analysis of cancer cell lines, and immunohistochemical studies of the clinical samples. We summarize some of these studies, detail several problems, and consider possible reasons for contradictory results and the needs for further research.

Role of differentiated embryo-chondrocyte expressed gene 2 in immunity

“…Specifically, Th2 cells are characterized by the expression of transcription factors such as GATA-3 and type 2 cytokines, including IL-4 ( 19 ). During immune responses, the Th2 cell population can significantly expand, serving as a crucial, albeit not exclusive, source of IL-4 ( 15 ).The expression of DEC2 is mediated by the IL-4/Stat6 pathway and can be further enhanced by ICOS or IL-25 ( 20 ). DEC2 expression is necessary to maintain the continuous differentiation of Th2 cells in later stages ( 7 ).…”

“…In periodontal tissue macrophages, DEC2 deficiency exacerbates periodontal inflammation and pyroptosis. In tumor immunity, DEC2 inhibits tumor growth and migration by regulating cell cycle proteins, epithelial–mesenchymal transition, and hypoxia-inducible factors ( 12 , 15 , 18 , 54 , 55 ). In autoimmune diseases, such as RA and SLE, DEC2 expression is abnormal and promotes the production of pathogenic factors such as IL-1β.…”

“…In addition, DEC2 regulates the differentiation of Th2 cells ( 7 ) and the self-renewal of alveolar macrophages (AMs) ( 14 ). DEC2 is also closely associated with tumors, with its transcription level serving as a marker of cancer progression ( 12 , 13 , 15 – 18 ).…”

BHLHE41 inhibits bladder cancer progression via regulation of PYCR1 stability and thus inactivating PI3K/AKT signaling pathway

“…Overexpression of BHLHE41 inhibits GC cell development in vitro and in vivo by inhibiting the ERK/NF-κB/EMT axis [20]. Furthermore, BHLHE41 was shown to have an oncogenic or suppressive function in lung cancer, clear cell renal cell carcinoma, and endometrial cancer [21][22][23]. However, the relevance and underlying mechanism of BHLHE41 in bladder cancer have not been studied.…”