Abstract
BackgroundHepatocellular carcinoma is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. Dysregulation of HomeoboxD10 (HOXD10) was found to suppress or promote cancer progression in different cancer types. The function and regulation of HOXD10 remain unclear in human hepatocellular carcinoma (HCC).MethodsPrimary HCC samples (117), normal liver tissue samples (15), and 13 HCC cell lines (SNU182, SNU449, HBXF344, SMMC7721, Huh7, HepG2, LM3, PLC/PRF/5, BEL7402, SNU387, SNU475, QGY7703, and Huh1) were included in this study. Methylation-specific PCR, flow cytometry, western blot, transwell, siRNA, and chromatin immunoprecipitation assays were employed.ResultsHOXD10 was methylated in 76.9% (90/117) of human primary HCC samples. HOXD10 methylation was significantly associated with vessel cancerous embolus, tumor cell differentiation, and the 3-year overall survival rate (all P < 0.05). The expression of HOXD10 was regulated by promoter region methylation. HOXD10 suppressed colony formation, cell proliferation, cell invasion and migration, and induced G2/M phase arrest and apoptosis in HCC cells. HOXD10 suppressed HCC cell xenograft growth in mice. HOXD10 suppresses HCC growth by inhibiting ERK signaling.ConclusionHOXD10 is frequently methylated in human HCC, and the expression of HOXD10 is regulated by promoter region methylation. HOXD10 suppresses HCC cell growth both in vitro and in vivo. HOXD10 suppresses human HCC by inhibiting ERK signaling.
Highlights
Hepatocellular carcinoma is the fifth most common malignancy and the third leading cause of cancer-related death worldwide
HOXD10 is silenced by promoter region hypermethylation in hepatocellular carcinoma (HCC) cells Semi-quantitative Reverse transcriptase polymerase chain reaction (RT-PCR) was employed to detect the expression of HOXD10 in HCC cells
methylation-specific PCR (MSP) primers were designed around the transcription start site in the CpG islands within the HOXD10 gene promoter region
Summary
Hepatocellular carcinoma is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. The function and regulation of HOXD10 remain unclear in human hepatocellular carcinoma (HCC). Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer-related death worldwide [1]. In China, HCC is the fourth most commonly diagnosed cancer in men, and it is the third leading cause of cancer death for both men and women [2]. Guo et al Clinical Epigenetics (2017) 9:116 development and carcinogenesis by modulating cell growth, migration, cell cycle, and apoptosis [11,12,13,14]. We analyzed the regulation and the function of HOXD10 in human HCC
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