MFAP2 Promotes the Proliferation of Cancer Cells and Is Associated With a Poor Prognosis in Hepatocellular Carcinoma

Abstract

Backgrounds: Microfibril-associated protein 2 (MFAP2) is an extracellular matrix protein that regulates the function of microfibrils by interacting with fibrillin. MFAP2 has been reported to play an important role in metabolic diseases and has been shown to be significantly overexpressed in head and neck squamous cell carcinoma and Hepatocellular carcinoma (HCC). However, the molecular function and prognostic value of MFAP2 have never been reported in HCC or other tumors. Methods: In the present study, expression characteristics of MFAP2 in HCC, its influence on the development of HCC, as well as its function and potential mechanism in HCC were verified by Quantitative reverse transcription-polymerase chain reaction, bioinformatics data mining and in vitro cell experiments. Results: MFAP2 was prominently high-expressed in HCC and associated with cancer stages. HCC patients with higher MFAP2 expression displayed lower overall survival (OS) and disease-specific survival(DSS), while there was no significant difference in recurrence-free survival (RFS). In vitro experiments showed that downregulation of MFAP2 inhibited proliferation, migration level of HCC cells. Transcription factors, DNA methyltransferases, immune factors may interact with MFAP2 mRNA to promote tumor progression in HCC. Conclusion: These findings suggest that MFAP2 may play a key role in the development of HCC. Therefore, MFAP2 may be a valuable prognostic marker and an effective anticancer target in HCC.

Upregulation of microfibrillar‑associated protein 2 is closely associated with tumor angiogenesis and poor prognosis in hepatocellular carcinoma

“…However, disease-induced fibrillin mutations may alter the ability of myofibrils to bind MFAP2, and lead to the occurrence and deterioration of the disease. Although some reports have described MFAP2 upregulation in HCC ( 14 ), its exact role therein remains unclear.…”

“…Consequently, MFAP2 is upregulated in breast cancer ( 8 ), thyroid cancer ( 9 ), melanoma ( 10 ), ovarian cancer ( 11 ) and gastric cancer ( 12 , 13 ), and associated with the occurrence and progression of these tumors. Previous studies have also shown that MFAP2 is upregulated in HCC ( 14 ), but its role in the occurrence and development of the disease is unclear. In order to investigate the role of MFAP2 in the occurrence and development of HCC, the aim of the present study was to evaluate the expression of MFAP2 in liver cancer by analyzing the tumor specimens and detailed clinical data of 94 patients.…”

HPV Infection Leaves a DNA Methylation Signature in Oropharyngeal Cancer Affecting Both Coding Genes and Transposable Elements

“…NNMT upregulation was already reported in oral squamous cell carcinoma [ 75 ], but its downregulation was associated with increased sensitivity to 5-fluorouracil in esophageal squamous cell carcinoma cells [ 76 ]. In contrast, MFAP2 upregulation was reported in head and neck cancer [ 77 ] and associated with poor prognosis in gastric and hepatocellular carcinomas [ 78 , 79 ]. Therefore, the downregulation of these genes in HPV-positive relative to HPV-negative OPSCC may contribute to the better prognosis and response to therapy observed in the first group of patients.…”

Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling

“…Different studies have described dysregulated MAGP-1 levels in diverse cancers underlining its implication in tumour progression, particularly in the processes of epithelial mesenchymal transition (EMT) due to its interaction with TGF-β [27]. In this sense, opposite gene expression levels of MFAP2 have been described in different tumour types as being upregulated in gastric [25], thyroid [33] and hepatocellular [34] carcinomas and downregulated in prostate carcinoma and paragangliomas [35].…”