Open AccessDNASE1L3 inhibits proliferation, invasion and metastasis of hepatocellular carcinoma by interacting with β‐catenin to promote its ubiquitin degradation pathway
Author(s) -
Li Bo,
Ge YuZhen,
Yan WeiWei,
Gong Bin,
Cao Kun,
Zhao Rui,
Li Chao,
Zhang YeWei,
Jiang YiHeng,
Zuo Shi
Publication year - 2022
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.13273
Subject(s) - ubiquitin , metastasis , hepatocellular carcinoma , catenin , cancer research , cell growth , in vivo , cytoplasm , cell , in vitro , biology , beta catenin , wnt signaling pathway , microbiology and biotechnology , chemistry , signal transduction , cancer , genetics , gene
As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic β‐catenin destruction complex (GSK‐3β and Axin), promotes the ubiquitination degradation of β‐catenin, and inhibits its nuclear transfer, thus, decreasing c‐Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.