Targeting endoplasmic reticulum stress-induced CLGN resensitizes hepatocellular carcinoma to apoptosis: paeonol synergistically enhances efficacy by dual inhibition of CLGN and NF-κB.

ABSTRACT:

Purpose

Endoplasmic reticulum stress (ERS) drives hepatocellular carcinoma (HCC) progression and therapy resistance. This study identifies Calmegin (CLGN) as a novel ERS-induced pro-survival factor and explores shCLGN combined with Paeonol (Pae) to overcome apoptosis resistance via NF-κB suppression.

Materials and methods

CLGN was discovered by transcriptome sequencing of tunicamycin (TM)-induced ERS in HepG2 cells and validated via Western blot. Clinical significance was assessed using 93 paired HCC/adjacent tissues (IHC/WB) and TCGA data. Functional roles of CLGN (proliferation: CCK-8/EdU; migration/invasion: Transwell; apoptosis: flow cytometry). shCLGN efficacy alone or with Pae was tested in vitro and in vivo (xenografts). Transcriptome sequencing combined

SUBMITTER: Yan S 

PROVIDER: S-EPMC12698408 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature