| RRC ID |
56668
|
| 著者 |
Jiang J, Liu Z, Ge C, Chen C, Zhao F, Li H, Chen T, Yao M, Li J.
|
| タイトル |
NK3 homeobox 1 (NKX3.1) up-regulates forkhead box O1 expression in hepatocellular carcinoma and thereby suppresses tumor proliferation and invasion.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality in China, and the molecular mechanism of uncontrolled HCC progression remains to be explored. NK3 homeobox 1 (NKX3.1), an androgen-regulated prostate-specific transcription factor, suppresses tumors in prostate cancer, but its role in HCC is unknown, especially in hepatocellular carcinoma. In the present study, the differential expression analyses in HCC tissues and matched adjacent noncancerous liver tissues revealed that NKX3.1 is frequently down-regulated in human primary HCC tissues compared with matched adjacent noncancerous liver tissues. We also noted that NKX3.1 significantly inhibits proliferation and mobility of HCC cells both in vitro and in vivo Furthermore, NKX3.1 overexpression resulted in cell cycle arrest at the G1/S phase via direct binding to the promoter of forkhead box O1 (FOXO1) and up-regulation of expression. Of note, FOXO1 silencing in NKX3.1-overexpressing cells reversed the inhibitory effects of NKX3.1 on HCC cell proliferation and invasion. Consistently, both FOXO1 and NKX3.1 were down-regulated in human HCC tissues, and their expression was significantly and positively correlated with each other. These results suggest that NKX3.1 functions as a tumor suppressor in HCC cells through directly up-regulating FOXO1 expression.
|
| 巻・号 |
292(47)
|
| ページ |
19146-19159
|
| 公開日 |
2017-11-24
|
| DOI |
10.1074/jbc.M117.793760
|
| PII |
S0021-9258(20)32889-1
|
| PMID |
28972178
|
| PMC |
PMC5702659
|
| MeSH |
Animals
Apoptosis
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology*
Case-Control Studies
Cell Cycle
Cell Movement
Cell Proliferation*
Forkhead Box Protein O1 / genetics
Forkhead Box Protein O1 / metabolism*
Gene Expression Regulation, Neoplastic*
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Liver Neoplasms / pathology*
Male
Mice
Mice, Inbred NOD
Mice, SCID
Neoplasm Invasiveness
Prognosis
Survival Rate
Transcription Factors / genetics
Transcription Factors / metabolism*
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
|
| IF |
4.106
|
| 引用数 |
10
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7 |
