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Loss of the Novel Mitochondrial Membrane Protein FAM210B Is Associated with Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is an aggressive and challenging disease to treat. Due to the lack of effective early diagnosis and therapy for the illness, it is crucial to identify novel biomarkers that can predict tumor behavior in HCC. In such cases, family with sequence similarity 210 member B (FAM210B) is abundant in various human tissues, but its regulatory mechanisms and role in various tissues remain unclear. In this study, we analyzed the expression pattern of FAM210B in HCC using public gene expression databases and clinical tissue samples. Our results confirmed that FAM210B was dysregulated in both HCC cell lines and HCC paraffin section samples. FAM210B depletion significantly increased the capacity of cells to grow, migrate, and invade in vitro, while overexpression of FAM210B suppressed tumor growth in a xenograft tumor model. Furthermore, we identified FAM210B's involvement in MAPK signaling and p-AKT signaling pathways, both of which are known oncogenic signaling pathways. In summary, our study provides a rational basis for the further investigation of FAM210B as a valuable biological marker for diagnosing and predicting the prognosis of HCC patients.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC10135939 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Loss of the Novel Mitochondrial Membrane Protein FAM210B Is Associated with Hepatocellular Carcinoma.

Zhou Yuanqin Y Pan Xianzhu X Liu Yakun Y Li Xiaofei X Lin Keqiong K Zhu Jicheng J Zhan Li L Kan Chen C Zheng Hong H

Biomedicines 20230421 4

Hepatocellular carcinoma (HCC) is an aggressive and challenging disease to treat. Due to the lack of effective early diagnosis and therapy for the illness, it is crucial to identify novel biomarkers that can predict tumor behavior in HCC. In such cases, family with sequence similarity 210 member B (FAM210B) is abundant in various human tissues, but its regulatory mechanisms and role in various tissues remain unclear. In this study, we analyzed the expression pattern of FAM210B in HCC using publi ...[more]

PMID: 37189851

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Project description:BackgroundComplex molecular events lead to development and progression of liver cirrhosis to HCC. Differentially expressed nuclear membrane associated proteins are responsible for the functional and structural alteration during the progression from cirrhosis to carcinoma. Although alterations/ post translational modifications in protein expression have been extensively quantified, complementary analysis of nuclear membrane proteome changes have been limited. Deciphering the molecular mechanism that differentiate between normal and disease state may lead to identification of biomarkers for carcinoma.ResultsMany proteins displayed differential expression when nuclear membrane proteome of hepatocellular carcinoma (HCC), fibrotic liver, and HepG2 cell line were assessed using 2-DE and ESI-Q-TOF MS/MS. From the down regulated set in HCC, we have identified for the first time a 15 KDa cytochrome b5A (CYB5A), ATP synthase subunit delta (ATPD) and Hemoglobin subunit beta (HBB) with 11, 5 and 22 peptide matches respectively. Furthermore, nitrosylation studies with S-nitrosocysteine followed by immunoblotting with anti SNO-cysteine demonstrated a novel and biologically relevant post translational modification of thiols of CYB5A in HCC specimens only. Immunofluorescence images demonstrated increased protein S-nitrosylation signals in the tumor cells and fibrotic region of HCC tissues. The two other nuclear membrane proteins which were only found to be nitrosylated in case of HCC were up regulated ATP synthase subunit beta (ATPB) and down regulated HBB. The decrease in expression of CYB5A in HCC suggests their possible role in disease progression. Further insight of the functional association of the identified proteins was obtained through KEGG/ REACTOME pathway analysis databases. String 8.3 interaction network shows strong interactions with proteins at high confidence score, which is helpful in characterization of functional abnormalities that may be a causative factor of liver pathology.ConclusionThese findings may have broader implications for understanding the mechanism of development of carcinoma. However, large scale studies will be required for further verification of their critical role in development and progression of HCC.

Dataset Information

Loss of the Novel Mitochondrial Membrane Protein FAM210B Is Associated with Hepatocellular Carcinoma.

Publications

Loss of the Novel Mitochondrial Membrane Protein FAM210B Is Associated with Hepatocellular Carcinoma.

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