title: H2.0-like homeobox 1 acts as a tumor suppressor in hepatocellular carcinoma.
abstract: H2.0-like homeobox 1 (HLX1) is a homeobox transcription factor gene expressed primarily in cytotrophoblast cell types in the early pregnancy human placenta and involved in the development of enteric nervous system. However, the biological function of HLX1 in hepatocellular carcinoma (HCC) remains unclear. In the present study, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR, western blot, and immunohistochemical staining were used to examine the expression level of HLX1 in a total of 125 cases of HCC tissues and their matched adjacent nontumorous tissues (ANLTs), and its correlation with clinical features of HCC patients was analyzed. Our findings showed that the expression level of HLX1 was significantly reduced in HCCs compared to ANLTs. Besides, it was also remarkably downregulated in HCC cell lines compared to normal liver cell line. We further found that the HLX1 level was significantly associated with the tumor size (p = 0.016), tumor number (p = 0.004), vascular invasion (p = 0.031), Edmondson-Steiner grade (p = 0.041), tumor-node-metastasis (TNM) stage (p < 0.001), and Barcelona clinic liver cancer (BCLC) stage (p = 0.008). Moreover, HLX1 was an independent risk factor for overall survival (OS, p = 0.020) and disease-free survival (DFS, p = 0.024) of HCC patients. In vitro experiments showed that overexpression of HLX1 markedly suppressed the invasion, migration, proliferation, and colony formation of HCC cells; in contrast, downregulation of HLX1 significantly promoted the invasion, migration, proliferation, and colony formation of HCC cells. In vivo study indicated that overexpression of HLX1 significantly inhibited the tumorigenic capacity of HCC cells in nude mice. Based on these findings, we suggest that HLX1 acts as a tumor suppressor in HCC.
authors.affiliation: Department of General Surgery, Second Xiangya Hospital, Central South University, Renmin Middle Road 139, Changsha, 410011, Hunan, China. liutingchenjing@sina.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Peace Hospital Changzhi Medical College, Changzhi, 046000, Shanxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Second Xiangya Hospital, Central South University, Renmin Middle Road 139, Changsha, 410011, Hunan, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Lei
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C084058:HLX protein, human; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors
keywords: H2.0-like homeobox 1; Hepatocellular carcinoma; Metastasis; Prognosis; Proliferation