Abstract
BackgroundHepatocellular carcinoma (HCC) is a common cause of cancer mortality worldwide. Recent studies have shown that the polytopic enzyme membrane associated ring-CH-type finger 6 (MARCH6) participates in tumorigenesis, but its function in HCC development needs to be investigated. This study aimed to explore the role of MARCH6 in HCC.MethodsExpression of MARCH6 in human HCC samples was checked by immunohistochemical staining assay. Clinical relevance of MARCH6 and activating transcription factor 2 (ATF2) was analyzed from TCGA database. CCK-8, EdU staining, colony formation and transwell were performed to assess cell proliferation, growth and migration. Xenografted tumorigenesis was used to examine in vivo role MARCH6. Immunoblotting was applied to detect protein abundance.ResultsWe found that MARCH6 expression was elevated in human HCC samples. Over-expression of MARCH6 was associated with poor prognosis of HCC patients. Up-expression of MARCH6 promoted cell growth and migration of HCC cells. In contrast, the HCC cell growth and migration were suppressed by MARCH6 knockdown. Furthermore, the DNA synthesis was enhanced by MARCH6. The expression of ATF2 was potentiated by MARCH6 over-expression, while it was suppressed by MARCH6 silencing. TCGA database showed positive correlation between the expression of MARCH6 and ATF2. Importantly, ATF2 expression contributed to the oncogenic function of HCC cells.ConclusionOur findings suggest that MARCH6-mediated ATF2 up-regulation contributes to HCC development. MARCH6 may be a promising target for the diagnosis and treatment of HCC.
Highlights
Hepatocellular carcinoma (HCC) is a common cause of cancer mortality worldwide
membrane associated ring-CH-type finger 6 (MARCH6) is highly expressed in human HCC cells Firstly, we evaluated the clinical relevance of MARCH6 from The Cancer Genome Atlas (TCGA) database
Spearman correlation analysis in TCGA HCC tissues revealed that MARCH6 was positively correlated with MKI67, CTNNB1, CDH2, FN1 and WNTSA, which were demonstrated as oncogene in cancer growth and metastasis (Supplementary Fig. 1)
Summary
Hepatocellular carcinoma (HCC) is a common cause of cancer mortality worldwide. Recent studies have shown that the polytopic enzyme membrane associated ring-CH-type finger 6 (MARCH6) participates in tumorigenesis, but its function in HCC development needs to be investigated. This study aimed to explore the role of MARCH6 in HCC. Protein ubiquitination is an important post-transcriptional modification that regulates protein stability. The stability of MARCH6 was regulated by ubiquitin-specific protease 19 [12]. Recent studies indicated that MARCH6 was positively corrected with androgen receptor (AR) gene expression, which shared common regulation with MARCH6 by the transcription factor Sp1 in prostate cancer [13]. Additional studies suggested that MARCH6 and IDOL E3 ubiquitin ligase circuit played a multifaceted role in the regulation of cholesterol homeostasis in hepatocytes [14]. The specific functions of MARCH6 in HCC remain unclear
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