Hypoxia-inducible factors drive miRNA-mediated downregulation of <i>L2HGDH</i> and <i>HIF1A</i> in clear cell renal cancer independent of 14q deletion.

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is characterized by pseudohypoxic signaling as well as metabolic and epigenetic aberrations of increasing severity during its pathogenesis and progression. Upon identifying that the markedly lower expression of L2HGDH and HIF1A in ccRCC tumors is not explained only by 14q deletion (⁓40% of ccRCC), we sought to elucidate the mechanisms underscoring their down-regulation independent of 14q deletion, given the marked translational and scientific importance. While lower L2HGDH was found to portend a strikingly worse prognosis in a multivariate survival analysis of ccRCC patients (n=509; TCGA) highlighting its translational importance, the lower expression of HIF1A in ccRCC despite the upregulated HIF1α protein (secondary to VH

SUBMITTER: Seal S 

PROVIDER: S-EPMC12637520 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature