| RRC ID |
86341
|
| 著者 |
Hirose K, Masuda T, Otsu H, Tobo T, Hosoda K, Abe T, Nakano Y, Hashimoto M, Tatsumi T, Ikehara T, Ofuchi T, Itoyama S, Ando Y, Tsuda Y, Yonemura Y, Sugimachi K, Oki E, Yoshizumi T, Mimori K.
|
| タイトル |
Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
Polarity genes form intracellular protein complexes that establish epithelial cell polarity and homeostasis for various normal cellular functions. Partitioning Defective 6B (PARD6B), a polarity gene, functions as a scaffold node for the Par protein complex. However, its contribution to colon cancer is not well understood. In this study, we showed that PARD6B regulates tumor progression in colorectal cancer (CRC). PARD6B is located on chromosome 20, which is frequently amplified in CRC, and its expression in CRC correlates with DNA copy number amplification, including enhancer regions. Immunohistochemistry and single-cell analyses also showed that PARD6B expression was significantly higher in cancer cells. Furthermore, unlike other polarity gene groups comprising the Par complex, PARD6B mRNA expression was the only independent poor prognostic factor. In vitro and in vivo experiments revealed that PARD6B positively regulates cell proliferation and cell cycle progression. In silico analysis also showed that PARD6B expression positively regulated MYC expression, a pathway believed to be associated. Additional in silico and in vitro analyses supported the hypothesis that PARD6B regulates miR-34c, which directly targets and represses MYC expression. Pan-cancer analysis indicated that PARD6B is highly expressed in gastrointestinal tumors, including CRC, and that high PARD6B mRNA expression is a poor prognostic factor in other cancer types. In summary, highly expressed PARD6B can promote CRC growth by upregulating MYC expression while suppressing miR-34c expression, making PARD6B a potential prognostic biomarker and therapeutic target for CRC.
|
| 巻・号 |
116(9)
|
| ページ |
2507-2522
|
| 公開日 |
2025-9-1
|
| DOI |
10.1111/cas.70119
|
| PMID |
40533910
|
| PMC |
PMC12400055
|
| MeSH |
Animals
Cell Line, Tumor
Cell Polarity / genetics
Cell Proliferation / genetics
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / metabolism
Colorectal Neoplasms* / pathology
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Mice
Mice, Nude
MicroRNAs / genetics
MicroRNAs / metabolism
Prognosis
Proto-Oncogene Proteins c-myc* / genetics
Proto-Oncogene Proteins c-myc* / metabolism
|
| IF |
4.966
|
| リソース情報 |
| ヒト・動物細胞 |
HCT116(RCB2979)
OLO205(RCB2127)
CACO‐2(RCB0988) |
