| RRC ID |
73016
|
| 著者 |
Kitayama S, Ikeda K, Sato W, Takeshita H, Kawakami S, Inoue S, Horie K.
|
| タイトル |
Testis-expressed gene 11 inhibits cisplatin-induced DNA damage and contributes to chemoresistance in testicular germ cell tumor.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Testicular germ cell tumor (TGCT) is a rare cancer but the most common tumor among adolescent and young adult males. Patients with advanced TGCT often exhibit a worse prognosis due to the acquisition of therapeutic resistance. Cisplatin-based chemotherapy is a standard treatment for advanced TGCTs initially sensitive to cisplatin, as exemplified by embryonal carcinoma. The acquisition of cisplatin resistance, however, could be a fatal obstacle for TGCT management. To identify cisplatin resistance-related genes, we performed transcriptome analysis for cisplatin-resistant TGCT cells compared to parental cells. In two types of cisplatin-resistant TGCT cell models that we established from patient-derived TGCT cells, and from the NEC8 cell line, we found that mRNA levels of the high-mobility-group nucleosome-binding gene HMGN5 and meiosis-related gene TEX11 were remarkably upregulated compared to those in the corresponding parental cells. We showed that either HMGN5 or TEX11 knockdown substantially reduced the viability of cisplatin-resistant TGCT cells in the presence of cisplatin. Notably, TEX11 silencing in cisplatin-resistant TGCT cells increased the level of cleaved PARP1 protein, and the percentage of double-strand break marker γH2AX-positive cells. We further demonstrated the therapeutic efficiency of TEX11-specific siRNA on in vivo xenograft models derived from cisplatin-resistant patient-derived TGCT cells. Taken together, the present study provides a potential insight into a mechanism of cisplatin resistance via TEX11-dependent pathways that inhibit apoptosis and DNA damage. We expect that our findings can be applied to the improvement of cisplatin-based chemotherapy for TGCT, particularly for TEX11-overexpressing tumor.
|
| 巻・号 |
12(1)
|
| ページ |
18423
|
| 公開日 |
2022-11-1
|
| DOI |
10.1038/s41598-022-21856-3
|
| PII |
10.1038/s41598-022-21856-3
|
| PMID |
36319719
|
| PMC |
PMC9626550
|
| MeSH |
Adolescent
Cell Line, Tumor
Cisplatin / pharmacology
DNA Damage
Drug Resistance, Neoplasm
HMGN Proteins
Humans
Male
Neoplasms, Germ Cell and Embryonal*
Testicular Neoplasms* / genetics
Testis / metabolism
Trans-Activators / genetics
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
NEC8(RCB0489) |
