論文 - 詳細
| RRC ID | 64357 |
|---|---|
| 著者 | Kurashima K, Shiozaki A, Kudou M, Shimizu H, Arita T, Kosuga T, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, Konishi E, Otsuji E. |
| タイトル | LRRC8A influences the growth of gastric cancer cells via the p53 signaling pathway. |
| ジャーナル | Gastric Cancer |
| Abstract |
BACKGROUND:Leucin-rich repeat containing protein A (LRRC8A), a component of the volume-regulated anion channel (VRAC), is activated by cell swelling and mediates regulatory volume decrease. We previously reported the expression of and important roles for several ion transporters in various gastrointestinal cancers, which have potential as novel targets for cancer treatment; however, the significance of LRRC8A in gastric cancer (GC) remains unclear. MATERIALS AND METHODS:Knockdown experiments were performed by transfecting human GC cell lines with LRRC8A siRNA. Gene expression was then assessed using microarray analysis. Samples from 132 patients with GC were subjected to immunohistochemistry (IHC) for LRRC8A, and its relationships with clinicopathological factors and prognosis were examined. RESULTS:The knockdown of LRRC8A suppressed the proliferation and movement of cells and enhanced apoptosis. The results of the microarray analysis showed the up- or down-regulated expression of genes related to the p53 signaling pathway (JNK, p53, p21, Bcl-2, and FAS) in LRRC8A-knockdown cells. IHC revealed a correlation between the expression of LRRC8A and the pT status (p = 0.015), and multivariate analysis identified the strong expression of LRRC8A as an independent prognostic factor for 5-year survival in GC patients (p = 0.0231). CONCLUSIONS:The present results indicate that LRRC8A functions as a mediator of and/or biomarker for GC. |
| 巻・号 | 24(5) |
| ページ | 1063-1075 |
| 公開日 | 2021-9-1 |
| DOI | 10.1007/s10120-021-01187-4 |
| PII | 10.1007/s10120-021-01187-4 |
| PMID | 33864161 |
| MeSH | Apoptosis Humans Membrane Proteins / genetics Membrane Proteins / metabolism Signal Transduction Stomach Neoplasms* / genetics Tumor Suppressor Protein p53* / genetics |
| IF | 7.088 |
| リソース情報 | |
| ヒト・動物細胞 | MKN7(RCB0999) MKN45(RCB1001) MKN74(RCB1002) HGC-27(RCB0500) NUGC-4(RCB1939) |