Insights into cAMP‐dependent molecular mechanisms regulating expression and function of LGALS16 gene in choriocarcinoma JEG‐3 cells

Abstract

The human choriocarcinoma cell line JEG‐3 offers a valuable model to study galectin‐16 gene (LGALS16) expression and functions in the context of placental cell differentiation and cancer cell biology. Recent evidence indicates that cAMP‐mediated signaling pathways might be responsible for the upregulation of LGALS16; however, the underlying mechanisms are unknown. Here, we employed biochemical inhibitors of the cAMP cascade and CRISPR/Cas9 engineered cells to assess regulatory patterns and associations between cAMP‐induced trophoblast differentiation and LGALS16 expression in JEG‐3 cells. The expression of LGALS16 was significantly upregulated in parallel with human chorionic gonadotropin beta (CGB), a biomarker of syncytiotrophoblast differentiation, in response to 8‐Br‐cAMP. Inhibition of p38 MAPK and EPAC significantly altered LGALS16 expression during differentiation, while PKA inhibition failed to change LGALS16 and CGB3/5 expression in our cell model. The CRISPR/Cas9 LGALS16 knockout cell pool expressed a significantly lower amount of CGB3/5, a reduced level of CGB protein, and an unaltered cell growth rate in response to 8‐Br‐cAMP in comparison with wild‐type JEG‐3 cells. Collectively, these findings suggest that LGALS16 is required for the trophoblast‐like differentiation of JEG‐3 cells, and its expression is mediated through p38 MAPK and EPAC signaling pathway branches.

Expression and secretion of galectin‐12 in the context of neutrophilic differentiation of human promyeloblastic HL‐60 cells

“…LGALS12 as a type of tumor suppressor gene cannot be excluded, similar to other tissue-specific galectins (Kaminker et al, 2024;Kim et al, 2013;Nagy, 2002;Satelli et al, 2011;Wiersma et al, 2013;Yang et al, 2001). These findings together allow us to suggest that the ATRA-induced phenotype of HL-60 cells with a high LGALS12 represents antitumorigenic N1 cells, while DMSO-induced phenotype with a low LGALS12 represents protumorigenic N2 cells (Figure 5), that is, LGALS12 may be considered as a regulatory marker of cell plasticity or polarization of neutrophils similar to macrophages (Lin et al, 2020;Wan et al, 2016).…”