Deoxyribonuclease 1-like 3 inhibits colorectal malignancy through antagonizing NEDD4-triggered CDKN1A ubiquitination

被引:0
作者
Yu, Lifei [1 ]
Huang, Jin [1 ]
机构
[1] Nanjing Med Univ, Changzhou 2 Peoples Hosp, Affiliated Hosp, Dept Gastroenterol, 29 Xinglong Ln, Changzhou 213000, Jiangsu, Peoples R China
关键词
CDKN1A; colorectal cancer; NEDD4; ubiquitination; PROMOTES PROLIFERATION; DNA FRAGMENTATION; CANCER CELLS; CARCINOMA; DNASE1L3; EXPRESSION; MIGRATION; DIAGNOSIS; BIOMARKER; CHROMATIN;
D O I
10.1002/cbin.12108
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Deoxyribonuclease 1-like 3 (DNASE1L3) has been shown to play nonnegligible roles in several types of carcinomas. Nevertheless, the biological function, clinical relevance, and influence of DNASE1L3 in colorectal cancer (CRC) remain obscure. Immunohistochemistry was adopted to examine DNASE1L3 and CDKN1A expression in CRC tissue, and the clinical significance of DNASE1L3 was assessed. Cell counting kit-8, colony formation, and transwell assays were employed for assessing tumor proliferation and migration. The mechanisms underlying the impact of DNASE1L3 were explored via western blot analysis, co-immunoprecipitation, and ubiquitination assay. It was observed that DNASE1L3 was downregulated in CRC tissues and was tightly associated with patient prognosis. DNASE1L3 impaired CRC cell proliferation and migration through elevating CDKN1A via suppressing CDKN1A ubiquitination. Meanwhile, DNASE1L3 was positively related to CDKN1A. In mechanism, DNASE1L3 and CDKN1A interacted with the E3 ubiquitin ligase NEDD4. Moreover, DNASE1L3 was competitively bound to NEDD4, thus repressing NEDD4-mediated CDKN1A ubiquitination and degradation. These discoveries implied the potential mechanisms of DNASE1L3 during tumorigenesis, suggesting that DNASE1L3 may serve as a new potential therapeutic agent for CRC.
引用
收藏
页码:325 / 333
页数:9
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