期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 9, 页码 4395-4407出版社
WILEY
DOI: 10.1111/jcmm.16503
关键词
cancer stem cell; cisplatin resistance; ISG15; KLF12; ovarian cancer
资金
- National Natural Science Foundation of China [81602510, 81872257, 81602439]
- Natural Science Foundation of Liaoning Province of China [2020-MS-185]
The study suggests that ISG15 may have context-dependent effects on tumor progression, with ISG15 being decreased in cisplatin-resistant ovarian cancer cells. Ectopic expression of ISG15 was found to inhibit CSC-like phenotypes and tumor formation, while downregulation of ISG15 promoted CSC-like features in cisplatin-sensitive ovarian cancer cells. Low ISG15 expression was associated with poor prognosis in ovarian cancer patients, indicating a potential therapeutic target.
Drug resistance is often developed during clinical chemotherapy of ovarian cancers. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) is possibly dependent on tumour context to promote or suppress progression of various tumours. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) was decreased in cisplatin-resistant ovarian cancer cells. The current study identified that both ectopic wild type and nonISGylatable mutant ISG15 expression inhibited CSC-like phenotypes of cisplatin-resistant ovarian cancer cells. Moreover, ectopic ISG15 expression suppressed tumour formation in nude mice. In addition, ISG15 downregulation promoted CSC-like features of cisplatin-sensitive ovarian cancer cells. Furthermore, low ISG15 expression was associated with poor prognosis in patients with ovarian cancer. Transcriptional repressor Kruppel-like factor 12 (KLF12) downregulated ISG15 in cisplatin-resistant cells. Our data indicated that downregulating ISG15 expression, via weakening effect of KLF12, might be considered as new therapeutic strategy to inhibit CSC phenotypes in the treatment of cisplatin-resistant ovarian cancer.
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