Open AccessISG15 is downregulated by KLF12 and implicated in maintenance of cancer stem cell‐like features in cisplatin‐resistant ovarian cancer
Author(s) -
Zhang Qi,
Wang Jiamei,
Qiao Huaiyu,
Huyan Lingyue,
Liu Baoqin,
Li Chao,
Jiang Jingyi,
Zhao Fuying,
Wang Huaqin,
Yan Jing
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16503
Subject(s) - isg15 , ovarian cancer , cancer research , cisplatin , ectopic expression , downregulation and upregulation , biology , cancer stem cell , cancer , cell culture , ubiquitin , gene , chemotherapy , genetics
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 Krüppel‐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.