MRPL42 Knockdown Suppresses the Malignant Functions of Hepatocellular Carcinoma by Regulating Oxidative Phosphorylation

Abstract

Objective

The diagnosis and treatment of hepatocellular carcinoma (HCC) remain unsatisfactory, underscoring the urgent need to explore new regulatory factors. This study aimed to uncover the regulatory role of mitochondrial ribosomal protein L42 (MRPL42) in HCC development and assess its clinical potential as a therapeutic target and prognostic biomarker.

Methods

MRPL42 expression in HCC was analyzed in datasets obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. MRPL42 expression was detected via reverse transcription quantitative polymerase chain reaction and immunohistochemistry, and its diagnostic and prognostic abilities were assessed via receiver operating characteristic (ROC) curves and Kaplan–Meier curves. Cell proliferation was assessed via the Cell Counting Kit-8 assay, migration via the wound healing assay, and invasion via Transwell experiments. The molecular mechanisms underlying MRPL42 knockdown-mediated suppression of HCC progression were analyzed via transcriptome sequencing. Western blot analysis was used to measure protein levels. The ATP content and mitochondrial respiratory chain complex I activity were determined via commercial reagent kits.

Results

MRPL42 overexpression predicted HCC occurrence and poor prognosis. MRPL42 knockdown suppressed the malignant functions of HCC. Transcriptomic analysis revealed that differentially expressed genes after MRPL42 knockdown were closely linked to oxidative phosphorylation (OXPHOS). MRPL42 knockdown inhibited the protein expression of the mitochondrial activity markers PGC-1α and MT-ND1 and reduced ATP content and mitochondrial respiratory chain complex I activity, indicating that MRPL42 deficiency impaired mitochondrial OXPHOS. Furthermore, MRPL42 knockdown suppressed the malignant functions of HCC cells by regulating OXPHOS.

Conclusion

MRPL42 is overexpressed in HCC and is a potential biomarker for HCC diagnosis and prognosis. In regulating OXPHOS, MRPL42 knockdown suppressed HCC malignant function, highlighting its potential as a therapeutic target.

Keywords

Hepatocellular carcinoma (HCC) / Mitochondrial respiratory chain / Metabolic reprogramming / Biomarker / MRPL42

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Funding

Guangxi Key Research and Development Program(no. AB22080064)

Guangxi Nanning Qingxiu District Key Research and Development Program of Science and Technology Plan(no. 2020050)

Guangxi Medical and Health Appropriate Technology Development, Promotion and Application Project(no. S2021097)

Guangxi Natural Science Foundation(No. 2017GXNSFAA198126，No.2014GXNSFAA118238)

the Foundation of Scientiffc Research and Technology Development Project of Guangxi Province, China (GuiKeGong1355005-3-5)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to the Huazhong University of Science and Technology