| RRC ID |
59648
|
| 著者 |
Zhou ZQ, Zhao JJ, Chen CL, Liu Y, Zeng JX, Wu ZR, Tang Y, Zhu Q, Weng DS, Xia JC.
|
| タイトル |
HUS1 checkpoint clamp component (HUS1) is a potential tumor suppressor in primary hepatocellular carcinoma.
|
| ジャーナル |
Mol Carcinog
|
| 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.
|
| 巻・号 |
58(1)
|
| ページ |
76-87
|
| 公開日 |
2019-1-1
|
| DOI |
10.1002/mc.22908
|
| PMID |
30182378
|
| MeSH |
Animals
Apoptosis
Biomarkers, Tumor / metabolism*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology*
Carcinoma, Hepatocellular / surgery
Case-Control Studies
Cell Cycle
Cell Cycle Proteins / metabolism*
Cell Movement
Cell Proliferation
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic*
Humans
Liver Neoplasms / metabolism
Liver Neoplasms / pathology*
Liver Neoplasms / surgery
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Prognosis
Survival Rate
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
|
| IF |
3.411
|
| 引用数 |
2
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7 |
