| RRC ID |
44784
|
| 著者 |
Sugihara H, Ishimoto T, Watanabe M, Sawayama H, Iwatsuki M, Baba Y, Komohara Y, Takeya M, Baba H.
|
| タイトル |
Identification of miR-30e* regulation of Bmi1 expression mediated by tumor-associated macrophages in gastrointestinal cancer.
|
| ジャーナル |
PLoS One
|
| Abstract |
Bmi1 is overexpressed in a variety of human cancers including gastrointestinal cancer. The high expression level of Bmi1 protein is associated with poor prognosis of gastrointestinal cancer patients. On the other hand, tumor-associated macrophages (TAMs) contribute to tumor growth, invasion, and metastasis by producing various mediators in the tumor microenvironment. The aim of this study was to investigate TAM-mediated regulation of Bmi1 expression in gastrointestinal cancer. The relationship between TAMs and Bmi1 expression was analyzed by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and results showed a positive correlation with tumor-infiltrating macrophages (CD68 and CD163) and Bmi1 expression in cancer cells. Co-culture with TAMs triggered Bmi1 expression in cancer cell lines and enhanced sphere formation ability. miRNA microarray analysis of a gastric cancer cell line co-cultured with macrophages was conducted, and using in silico methods to analyze the results, we identified miR-30e* as a potential regulator of Bmi1 expression. Luciferase assays using miR-30e* mimic revealed that Bmi1 was a direct target for miR-30e* by interactions with the putative miR-30e* binding sites in the Bmi1 3' untranslated region. qRT-PCR analysis of resected cancer specimens showed that miR-30e* expression was downregulated in tumor regions compared with non-tumor regions, and Bmi1 expression was inversely correlated with miR-30e* expression in gastric cancer tissues, but not in colon cancer tissues. Our findings suggest that TAMs may cause increased Bmi1 expression through miR-30e* suppression, leading to tumor progression. The suppression of Bmi1 expression mediated by TAMs may thus represent a possible strategy as the treatment of gastrointestinal cancer.
|
| 巻・号 |
8(11)
|
| ページ |
e81839
|
| 公開日 |
2013-1-1
|
| DOI |
10.1371/journal.pone.0081839
|
| PII |
PONE-D-13-27717
|
| PMID |
24312366
|
| PMC |
PMC3842972
|
| MeSH |
Base Sequence
Blotting, Western
Cell Line, Tumor
Coculture Techniques
Gastrointestinal Neoplasms / genetics*
Gastrointestinal Neoplasms / pathology
Gene Expression Regulation*
Humans
Macrophages / metabolism*
MicroRNAs / genetics*
Oligonucleotide Array Sequence Analysis
Polycomb Repressive Complex 1 / genetics
Polycomb Repressive Complex 1 / metabolism*
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
|
| IF |
2.74
|
| 引用数 |
40
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
NUGC-4(RCB1939)
THP-1(RCB1189) |
