Validation of ZMYND8 as a new treatment target in hepatocellular carcinoma

• Published in: Journal of cancer research and clinical oncology 2021-12, Vol.147 (12), p.3517-3534
• Main Authors: Choi, Sangjoon, Lee, Keun-Woo, Koh, Hyun Hee, Park, Sujin, Yeo, So-Young, Joh, Jae-Won, Choi, Moon Seok, Kim, Seok-Hyung, Park, Cheol-Keun, Ha, Sang Yun
• Format: Article
• Language: English
• Subjects: Apoptosis; Cancer Research; DNA microarrays; Gene expression; Hematology; Hepatocellular carcinoma; Immunohistochemistry; Internal Medicine; Liver cancer; Medical prognosis; Medicine; Medicine & Public Health; Microvasculature; Oncology; Original Article – Cancer Research; Patients; Proteins; Tumorigenicity; Tumors; Xenografts; Zinc finger proteins; α-Fetoprotein
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-021-03768-3

Background ZMYND8 (Zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8) has been known to play an important role in tumor regulation in various types of cancer. However, the results of ZMYND8 expression and their clinical significance in hepatocellular carcinoma (HCC) have not yet been published. In the present study, we investigate the expression of ZMYND8 protein and mRNA in HCC and elucidate its prognostic significance. Methods ZMYND8 protein and mRNA expression in 283 and 234 HCCs were investigated using immunohistochemistry and microarray gene expression profiling data. The relationships between ZMYND8 expression with clinicopathologic features and prognosis of HCC patients were evaluated. Furthermore, we performed the invasion, migration, apoptosis, soft agar formation assay and sphere formation assay in HCC cell lines, and evaluated tumorigenicity in a nude mouse model, after ZMYND8 knockdown. Results Overexpression of ZMYND8 protein and mRNA was observed in 20.5% and 26.9% of HCC cases, respectively. High ZMYND8 expression showed significant correlations with microvascular invasion, high Edmondson grade, advanced American Joint Committee on Cancer, and increased alpha-fetoprotein level. ZMYND8 mRNA overexpression was an independent prognostic factor for predicting early recurrence as well as short recurrence-free survival (RFS). Downregulation of ZMYND8 reduced migration and invasion of HCC cells, and promoted apoptosis of HCC cells in an in vitro model. In a xenograft nude mouse model, knockdown of ZMYND8 significantly reduced tumor growth. Conclusion ZMYND8 mRNA overexpression could be a prognostic marker of shorter RFS in HCC patients after curative resection. ZMYND8 might play an important role in the proliferation and progression of HCC and could be a promising candidate for targeted therapy.