Open AccessTSG 101 promotes the proliferation, migration and invasion of hepatocellular carcinoma cells by regulating the PEG 10
Author(s) -
Liu Zhiyi,
Tian Zilu,
Cao Kuan,
Zhang Bin,
Wen Quan,
Zhou Xinyu,
Yang Weibin,
Wang Tao,
Shi Hengliang,
Wang Renhao
Publication year - 2019
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.13878
Subject(s) - hepatocellular carcinoma , matrix metalloproteinase , cancer research , cell growth , cell migration , microbiology and biotechnology , cell , chemistry , biology , genetics
The tumour susceptibility gene 101 ( TSG 101) is reported to play important roles in the development and progression of several human cancers. However, its potential roles and underlined mechanisms in human hepatocellular carcinoma ( HCC ) are still needed to be further clarified. In the present study, we reported that knock down of TSG 101 suppressed the proliferation, migration and invasion of HCC cells, while overexpression of TSG 101 facilitated them. Molecularly, the results revealed that knock down of TSG 101 significantly decreased the cell cycle related regulatory factor p53 and p21. In another point, knock down of TSG 101 also obviously decreased the level of metallopeptidase inhibitor TIMP 1 (Tissue inhibitors of metalloproteinases 1), which results in inhibition of MMP 2, MMP 7 and MMP 9. In contrast, overexpression of TSG 101 had opposite effects. The iTRAQ proteomics analysis identified that oncogenic protein PEG 10 (Paternally expressed gene 10) might be a potential downstream target of TSG 101. Further investigation showed that TSG 101 interacted with PEG 10 and protected it from proteasomal degradation thereby regulating the expression of p53, p21 and MMP s. Finally, we found that both TSG 101 and PEG 10 proteins are up‐regulated and presented a direct correlation in HCC patients. In conclusion, these results suggest that TSG 101 is up‐regulated in human HCC patients, which may accelerate the proliferation, migration and invasion of HCC cells through regulating PEG 10.