Abstract
Solute carrier family 25 member 20 (SLC25A20) is a mitochondrial-membrane–carrier protein involved in the transport of acylcarnitines into mitochondrial matrix for oxidation. A previous-integrated-proteogenomic study had identified SLC25A20 as one of the top-three prognostic biomarkers in HCC. However, the expression and the biological function of SLC25A20 have not yet been investigated in HCC. In the present study, we found that SLC25A20 expression is frequently down-regulated in HCC cells mainly due to the up-regulation of miR-132-3p. Down-regulation of SLC25A20 is associated with a poor prognosis in patients with HCC. SLC25A20 suppressed HCC growth and metastasis, both in vitro and in vivo, by suppression of G1–S cell transition, epithelial-to-mesenchymal transition (EMT), and induction of cell apoptosis. Mechanistically, SLC25A20 down-regulation promoted HCC growth and metastasis through suppression of fatty-acid oxidation. Altogether, SLC25A20 plays a critical tumor-suppressive role in carcinogenesis of HCC; SLC25A20 may serve as a novel prognostic factor and therapeutic target for patients with HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide[1]
To determine whether the protein-expression level of SLC25A20 is decreased in HCC tissues, we performed immunohistochemical analysis to further analyze the expression of SLC25A20 in the paired tumor and the peritumor tissues from another 226 patients with HCC
Kaplan–Meier survival analysis further indicated that patients with HCC, with low expression levels of SLC25A20, had a significant shorter overall survival (OS) and recurrence-free survival (RFS) compared with those patients with high SLC25A20 expression levels (Fig. 1F), which was validated by bioinformatic analysis based on the online web portal Kaplan–Meier Plotter[12] (Fig. 1G)
Summary
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide[1]. Most patients are diagnosed with it in advanced stages due to the lack of specific molecular markers for early detection. In spite of the great progressions that have been made during the recent years, the effective therapies for HCC are still limited, owing to the poor understanding of the molecular mechanisms underlying the metastatic growth of HCC2,3. It is critical to identify novel molecular mechanisms involved in the carcinogenesis of HCC, which could. The solute carrier family 25 member 20 (SLC25A20), known as carnitine/acylcarnitine transporter (CACT), is a mitochondrial-membrane–carrier protein involved in the transport of acylcarnitines into mitochondrial matrix for oxidation[4,5]. Mutations in SLC25A20 are usually lethal in the newborns and infants[9], further implying its critical physiological functions. A mass spectrometry (MS)-based proteomics study in a large cohort of tumor tissues from 159 HBV-related HCC patients has identified SLC25A20 as one of the robust and representative prognostic proteins in HCC10, implying that
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