Hepatocellular carcinoma ferroptosis associative long non-coding RNA (HEPFAL)

Hepatocellular carcinoma ferroptosis associative long non-coding RNA (HEPFAL/KB-68A7.1) is a 644-nucleotide cytoplasm-enriched lncRNA identified as a tumor suppressor in HCC. Low expression of HEPFAL is correlated with larger tumors, higher aggressiveness, and poor prognosis in HCC patients[1][2]. Mechanistically, HEPFAL binds the histone methyltransferase NSD1, sequestering it in the cytoplasm, thereby decreasing its nuclear availability. This leads to reduced activation of oncogenic targets, notably WNT10B, via decreased H3K36 di-methylation and increased H3K27 tri-methylation at target promoters, repressing activation of the Wnt/β-catenin signaling pathway—critical for HCC growth and metastasis[1][2]. HEPFAL also accelerates ferroptosis (an iron-dependent, non-apoptotic cell death pathway) by reducing expression of SLC7A11, further suppressing HCC progression[3]. Thus, HEPFAL is emerging as a novel molecular target for both prognosis and possibly therapeutic intervention in HCC.

Other names

HEPFALKB-68A7.1

Drugs targeting HEPFAL (KB-68A7.1) would likely modulate its interaction with NSD1, influencing histone methylation, WNT10B expression, and thereby repressing Wnt/β-catenin signaling. Potential promotion of ferroptosis by reducing SLC7A11 expression, increasing susceptibility of HCC cells to ferroptotic cell death.