[NPLOC4 promotes proliferation, invasion, and migration of hepatocellular carcinoma cells via enhancing Wnt/β-catenin-mediated mitophagy].
Dysregulation of mitophagy contributes to the initiation and progression of hepatocellular carcinoma (HCC). Nuclear protein localization 4 homolog (NPLOC4) is an essential protein involved in various cellular processes and has been implicated in multiple cancers. Recent studies have suggested that NPLOC4 participates in the regulation of mitophagy; however, its role in HCC remains unclear. This study aims to investigate the role of NPLOC4 in mitophagy and its underlying regulatory mechanisms in HCC.
RNA sequencing data from the GSE277232 and GSE251942 datasets obtained from the Gene Expression Omnibus (GEO) database were analyzed together with mitophagy-related genes collected from the GeneCards database to identify differentially expressed mitophagy-related genes in HCC. NPLOC4 expression was further analyzed and validated by Western blotting. Small interfering RNA (siRNA)-mediated knockdown of NPLOC4 was performed in HCC cells for functional loss-of-function assays. Mitophagy levels were evaluated by analyzing the expression of mitophagy-related proteins, transmission electron microscopy, and immunofluorescence staining.
Bioinformatics analysis identified NPLOC4 as a key differentially expressed mitophagy-related gene. NPLOC4 was significantly upregulated in HCC tissues and was associated with poor clinical prognosis (all P<0.05). Knockdown of NPLOC4 inhibited HCC cell proliferation, migration, and invasion, while promoting apoptosis (all P<0.05). In addition, NPLOC4 knockdown suppressed mitophagy and the Wnt/β-catenin signaling pathway in HCC cells (all P<0.05). Treatment with the Wnt agonist BML-284 abolished the inhibitory effect of NPLOC4 knockdown on mitophagy (P<0.05), indicating that NPLOC4 regulates mitophagy through activation of the Wnt/β-catenin pathway. Furthermore, treatment with the mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazone (CCCP) reversed the inhibitory effects of NPLOC4 knockdown on HCC cell proliferation, migration, and invasion (all P<0.05), suggesting that NPLOC4 silencing suppresses HCC progression by regulating mitophagy.
NPLOC4 is highly expressed in HCC. Downregulation of NPLOC4 inhibits activation of the Wnt/β-catenin signaling pathway, thereby inhibiting mitophagy and ultimately inhibiting HCC cell proliferation, migration, and invasion. These findings suggest that NPLOC4 may serve as a potential biomarker and therapeutic target for HCC.
RNA sequencing data from the GSE277232 and GSE251942 datasets obtained from the Gene Expression Omnibus (GEO) database were analyzed together with mitophagy-related genes collected from the GeneCards database to identify differentially expressed mitophagy-related genes in HCC. NPLOC4 expression was further analyzed and validated by Western blotting. Small interfering RNA (siRNA)-mediated knockdown of NPLOC4 was performed in HCC cells for functional loss-of-function assays. Mitophagy levels were evaluated by analyzing the expression of mitophagy-related proteins, transmission electron microscopy, and immunofluorescence staining.
Bioinformatics analysis identified NPLOC4 as a key differentially expressed mitophagy-related gene. NPLOC4 was significantly upregulated in HCC tissues and was associated with poor clinical prognosis (all P<0.05). Knockdown of NPLOC4 inhibited HCC cell proliferation, migration, and invasion, while promoting apoptosis (all P<0.05). In addition, NPLOC4 knockdown suppressed mitophagy and the Wnt/β-catenin signaling pathway in HCC cells (all P<0.05). Treatment with the Wnt agonist BML-284 abolished the inhibitory effect of NPLOC4 knockdown on mitophagy (P<0.05), indicating that NPLOC4 regulates mitophagy through activation of the Wnt/β-catenin pathway. Furthermore, treatment with the mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazone (CCCP) reversed the inhibitory effects of NPLOC4 knockdown on HCC cell proliferation, migration, and invasion (all P<0.05), suggesting that NPLOC4 silencing suppresses HCC progression by regulating mitophagy.
NPLOC4 is highly expressed in HCC. Downregulation of NPLOC4 inhibits activation of the Wnt/β-catenin signaling pathway, thereby inhibiting mitophagy and ultimately inhibiting HCC cell proliferation, migration, and invasion. These findings suggest that NPLOC4 may serve as a potential biomarker and therapeutic target for HCC.