J Cancer 2022; 13(1):225-242. doi:10.7150/jca.63608 This issue

Research Paper

Epigenetic modifications inhibit the expression of MARVELD1 and in turn tumorigenesis by regulating the Wnt/β-catenin pathway in pan-cancer

Jingchun Zhang1,2, Qingwei Li1,2, Qinliang Sun3, Bojun Wang1,2, Ying Cui1,2, Changjie Lou1,2, Yuanfei Yao1,2✉, Yanqiao Zhang1✉

1. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
2. Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang Province, China.
3. Department of Ultrasound, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

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Zhang J, Li Q, Sun Q, Wang B, Cui Y, Lou C, Yao Y, Zhang Y. Epigenetic modifications inhibit the expression of MARVELD1 and in turn tumorigenesis by regulating the Wnt/β-catenin pathway in pan-cancer. J Cancer 2022; 13(1):225-242. doi:10.7150/jca.63608. Available from https://www.jcancer.org/v13p0225.htm

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Graphic abstract

MARVEL domain-containing 1 (MARVELD1) is one of the MARVEL domain-containing proteins. Expression of MARVELD1 in tumor and non-tumor tissues, the relationship between its expression and cancer prognosis, and upstream regulation of MARVELD1 were examined using pan-cancer data from The Cancer Genome Atlas. MARVELD1 expression was significantly downregulated in tissues used for pan-cancer analysis compared to that in normal tissues. Low expression of MARVELD1 was associated with poor disease outcomes in pan-cancer. Colon cancer patients with low expression of MARVELD1 had worse progression free survival and overall survival than those with high expression levels in our cohort. Hypermethylation and histone modification in the MARVELD1 promoter locus synergistically affected its expression in pan-cancer. The function of MARVELD1 in colon cancer remains to be studied. Gene Ontology enrichment analysis revealed that MARVELD1 may modulate processes associated with inhibition of tumorigenesis in colon cancer. Both upstream transcription factors and downstream functional enrichment of MARVELD1 were related to the Wnt/β-catenin signaling pathway. Overexpression of MARVELD1 inhibited the expression of β-catenin and its entry into the nucleus. MARVELD1 also inhibited the proliferation, migration, and invasion of colon cancer cells. With Wnt/β-catenin activator LiCl treatment, rescue experiments demonstrated that the role of MARVELD1 in colon cancer progression was dependent on the Wnt/β-catenin pathway. These results indicate that MARVELD1 acts as a tumor suppressor and inhibits tumorigenesis via the Wnt/β-catenin pathway.

Keywords: MARVELD1, prognosis, epigenetic modification, pan-cancer, Wnt pathway