HUS1 checkpoint clamp component (HUS1) is a potential tumor suppressor in primary hepatocellular carcinoma

Abstract

The HUS1 checkpoint clamp component (HUS1), which is a member of an evolutionarily conserved, genotoxin-activated checkpoint complex (Rad9-Rad1-Hus1 [9-1-1] complex), is involved in cell cycle arrest and DNA repair in response to DNA damage. We conducted this study to investigate the biological significances of HUS1 expression in hepatocellular carcinoma (HCC) development. The mRNA and protein expression levels of HUS1 were determined using Real-time PCR and Western blot, respectively. One hundered and twenty four paraffin sections from HCC tissues were analyzed by immunohistochemistry to assess the association between HUS1 expression and clinicopathological characteristics of patients. The Kaplan-Meier method was performed to calculate the OS and RFS curves. Cell proliferation and colony formation assays, cell migration and invasion assays and cell cycle assays were used to determine the suppressor role of HUS1 in vitro. A mouse model was used to determine the effect of HUS1 on tumorigenesis. The expression of HUS1 was significantly decreased in HCC cell lines and tissues, and low HUS1 expression was associated with poor prognosis of HCC patients. Upregulation of HUS1 expression inhibited the cell proliferation, colony formation, migration, and invasion, as well as arrested cell cycle at G0/G1 in HCC cells in vitro. Moreover, sufficient HUS1 expression inhibited the tumor growth in nude mice. Our study revealed for the first time that HUS1 is a potential tumor suppressor that might produce an antitumor effect in human HCC. Furthermore, HUS1 may serve as a prognostic indicator and could be used for therapeutic application in HCC patients.

SEC61G identified as a prognostic biomarker of head and neck squamous cell carcinoma

“…HUS1, an important DNA damage checkpoint, participates in the regulation of the cell cycle [22,23]. HUS1 can act as a potential tumor suppressor of hepatocellular carcinoma [24]. However, there is still no report regarding the potential correlation between HUS1 expression and oncogenesis in HNSCC.…”

Prognosis and modulation mechanisms of COMMD6 in human tumours based on expression profiling and comprehensive bioinformatics analysis

“…3 Gene dysregulation, such as activation of oncogenes and inactivation of tumour suppressing genes, is a common trait of human cancers and have been involved in each of these hallmarks. 4,5 Therefore, a better understanding of key tumour-driven genes will help to elucidate the mechanism of tumorigenesis at the molecular level, as well as improve the accurate prevention and treatment of malignant tumours.…”

Insight into the Web of Stress Responses Triggered at Gene Expression Level by Porphyrin-PDT in HT29 Human Colon Carcinoma Cells

“…PDT-induced DNA damage was indirectly evidenced by the upregulation of eight genes involved in DNA damage repair mechanisms, such as cell cycle arrest ( CDKN1A [ 34 ], GADD45A / G [ 35 ], CHEK2 [ 36 ] and HUS1 [ 37 ], or other DNA damage responses ( DDIT3 [ 38 ], DDB2 [ 39 ] and XPC [ 40 ] ( Table 2 ). As shown in Figure 10 d, the CDKN1A and GADD45A genes involved in cell cycle arrest were found overexpressed in both adhered and detached cells.…”