| RRC ID |
86056
|
| 著者 |
Fang N, Liu B, Pan Q, Gong T, Zhan M, Zhao J, Wang Q, Tang Y, Li Y, He J, Xiang T, Sun F, Lu L, Xia J.
|
| タイトル |
SMG5 Inhibition Restrains Hepatocellular Carcinoma Growth and Enhances Sorafenib Sensitivity.
|
| ジャーナル |
Mol Cancer Ther
|
| Abstract |
Hepatocellular carcinoma (HCC) has a pathogenesis that remains elusive with restricted therapeutic strategies and efficacy. This study aimed to investigate the role of SMG5, a crucial component in nonsense-mediated mRNA decay (NMD) that degrades mRNA containing a premature termination codon, in HCC pathogenesis and therapeutic resistance. We demonstrated an elevated expression of SMG5 in HCC and scrutinized its potential as a therapeutic target. Our findings revealed that SMG5 knockdown not only inhibited the migration, invasion, and proliferation of HCC cells but also influenced sorafenib resistance. Differential gene expression analysis between the control and SMG5 knockdown groups showed an upregulation of methionine adenosyltransferase 1A in the latter. High expression of methionine adenosyltransferase 1A, a catalyst for S-adenosylmethionine (SAM) production, as suggested by The Cancer Genome Atlas data, was indicative of a better prognosis for HCC. Further, an ELISA showed a higher concentration of SAM in SMG5 knockdown cell supernatants. Furthermore, we found that exogenous SAM supplementation enhanced the sensitivity of HCC cells to sorafenib alongside changes in the expression of Bax and Bcl-2, apoptosis-related proteins. Our findings underscore the important role of SMG5 in HCC development and its involvement in sorafenib resistance, highlighting it as a potential target for HCC treatment.
|
| 巻・号 |
23(8)
|
| ページ |
1188-1200
|
| 公開日 |
2024-8-1
|
| DOI |
10.1158/1535-7163.MCT-23-0729
|
| PII |
743186
|
| PMID |
38647536
|
| MeSH |
Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Apoptosis / drug effects
Carcinoma, Hepatocellular* / drug therapy
Carcinoma, Hepatocellular* / genetics
Carcinoma, Hepatocellular* / metabolism
Carcinoma, Hepatocellular* / pathology
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation* / drug effects
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic / drug effects
Humans
Liver Neoplasms* / drug therapy
Liver Neoplasms* / genetics
Liver Neoplasms* / metabolism
Liver Neoplasms* / pathology
Methionine Adenosyltransferase / genetics
Methionine Adenosyltransferase / metabolism
Mice
Sorafenib* / pharmacology
|
| IF |
5.615
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7 |
