CTNNB1 Knockdown Inhibits Cell Proliferation and Aldosterone Secretion Through Inhibiting Wnt/β-Catenin Signaling in H295R Cells

Abstract

Aldosterone-producing adenomas (APA) is one of the causative factors of primary aldosteronism. Previous studies have suggested that there are somatic CTNNB1 mutations in APA, but the specific mechanism of CTNNB1 mutation in APA tumorigenesis and aldosterone secretion remains unclear. In the present study, human adrenocortical carcinoma cell line H295 R was used to establish stable CTNNB1 knockdown cell lines. Cell proliferation and aldosterone secretion of H295 R cells in response to angiotensin Ⅱ (Agn Ⅱ) were analyzed. We found that CTNNB1 knockdown reduced β-catenin expression and inhibited proliferation of H295 R cells. CTNNB1 knockdown inhibited Wnt/β-catenin signaling pathway and downregulated expression of downstream genes including axin 2, lymphoid enhancer binding factor 1 ( LEF1), and cyclin D1. In addition, CTNNB1 knockdown decreased responses of H295 R cells to Agn Ⅱ and decreased aldosterone secretion. Our findings suggest that CTNNB1 knockdown can inhibit H295 R cell proliferation and decrease aldosterone secretion in the responses of H295 R cells to Ang II through inhibiting Wnt/β-catenin signaling pathway, indicating that targeting Wnt/β-catenin signaling pathway may be an important approach to decrease aldosterone secretion in the treatment of aldoster-producing adenomas.

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause

“…Both interventions reduced the aldosterone production relative to vehicle-treated cells, as anticipated by published experiments (Fig. 2c,d) 22,23 . However, neither silencing of CTNNB1 nor ICG-001 blunted the fold-increase in aldosterone secretion seen in mutant-transfected cells compared to wild-type (Fig.…”

Determination of WWOX Function in Modulating Cellular Pathways Activated by AP-2α and AP-2γ Transcription Factors in Bladder Cancer

“…Along with AKT3, they repress one another but seem to also be regulated by other mechanisms since high AKT3 level during AP-2γ did not inhibit GSK3B, similar to CTNNB1. Nevertheless, the last two increase proliferation when overexpressed [92,93] which certifies the above data on WWOX or AP-2γ.…”

Diabetes mellitus induces a novel inflammatory network involving cancer progression: Insights from bioinformatic analysis and in vitro validation

“…Analysis of single-cell RNA sequencing of COAD. pathway and downregulates the expression of downstream genes, including axin 2, lymphoid enhancer-binding factor 1 (LEF1), and cyclin D1, thereby inhibiting tumor proliferation (36). In our study, CTNNB1 was highly expressed in all the tumors except CESC, OV, UCEC, and UCS, confirming its carcinogenicity.…”

“…On the one hand, CTNNB1 promotes tumor development and progression through Survivin, which inhibits apoptosis, promotes cell cycle progression, and enhances angiogenesis ( 35 ). On the other hand, CTNNB1 knockdown inhibits the Wnt/β-catenin signaling pathway and downregulates the expression of downstream genes, including axin 2, lymphoid enhancer-binding factor 1 ( LEF1 ), and cyclin D1, thereby inhibiting tumor proliferation ( 36 ). In our study, CTNNB1 was highly expressed in all the tumors except CESC, OV, UCEC, and UCS, confirming its carcinogenicity.…”