Characterizing the tumor suppressor activity of FLCN in Birt-Hogg-Dube syndrome cell models through transcriptomic and proteomic analysis.

ABSTRACT: Birt-Hogg-Dubé syndrome (BHD) patients are uniquely susceptible to all renal tumor subtypes. However, the underlying mechanism of carcinogenesis is unclear. To study cancer development in BHD, we used human proximal kidney (HK2) cells and found that long-term folliculin (FLCN) knockdown was required to increase the tumorigenic potential of these cells, as evidenced by the formation of larger spheroids under nonadherent conditions. Transcriptomic and proteomic analyses revealed links between the FLCN, cell cycle control and DNA damage response (DDR) machinery. In addition, HK2 cells lacking FLCN had an altered transcriptome profile and enriched cell cycle control genes. G₁/S cell cycle checkpoint signaling was compromised by increased protein levels of cyclin D1 (CCND1) and hyper

SUBMITTER: Jones RA 

PROVIDER: S-EPMC12143978 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature