Ubiquitin specific peptidase 5 mediates Histidine‐rich protein Hpn induced cell apoptosis in hepatocellular carcinoma through P14‐P53 signaling

Abstract

Hpn is a small histidine-rich cytoplasmic protein from Helicobacter pylori and has been recognized as a high-risk factor for several cancers including gastric cancer, colorectal cancer, and MALT lymphoma. However, the relationship between Hpn and cancers remains elusive. In this study, we discovered that Hpn protein effectively suppressed cell growth and induced apoptosis in hepatocellular carcinoma (HCC). A two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics was performed to find the molecular targets of Hpn in HCC cells. It was identified that twelve proteins were differentially expressed, with USP5 being one of the most significantly downregulated protein. The P14 -P53 signaling was activated by USP5 knockdown in HCC cells. Furthermore, USP5 overexpression significantly rescued the suppressive effect of Hpn on the viability of HCC cells. In conclusion, our study suggests that Hpn plays apoptosis-inducing roles through suppressing USP5 expression and activating the P14 -P53 signaling. Therefore, Hpn may be a potential candidate for developing novel anti-HCC drugs.

Ubiquitin specific peptidase 5 enhances STAT3 signaling and promotes migration and invasion in Pancreatic Cancer

“…Also, USP22 is responsible for hepatocellular carcinoma migration 19 . USP5 has been reported in targeting several proteins, such as P53, FOXM1, SLUG, βcatenin, c-Maf, TUFM, HDAC2 et al 4 - 9 , 20 , 21 . USP5 has also been implicated in a wide variety of cellular events, such as the efficient repair of DNA Double-Strand Breaks, alternative RNA Splicing, neural pain, tumor cell proliferation and progression 6 , 9 , 15 , 16 , 22 .…”

“…USP5 has also been implicated in a wide variety of cellular events, such as the efficient repair of DNA Double-Strand Breaks, alternative RNA Splicing, neural pain, tumor cell proliferation and progression 6 , 9 , 15 , 16 , 22 . Intriguingly, USP5 has been confirmed to mediate p53 signaling 20 , wnt-β-catenin pathway 5 , Type I interferon signaling pathway 23 , Notch and RTK signaling pathway 24 . A recent study confirmed that upregulated USP5 can promote pancreatic cancer 10 .…”

Discovery of small molecule antagonists of the USP5 zinc finger ubiquitin-binding domain

“…USP5 has been associated with tumorigenesis [15][16][17][18][19] , neurodegeneration [20][21][22] , and viral infections 23,24 . In addition, USP5 plays a role in regulation of ubiquitin levels in DNA damage repair 25 and stress granules 26 .…”

IMPDH2 promotes cell proliferation and epithelial‑mesenchymal transition of non‑small cell lung cancer by activating the Wnt/β‑catenin signaling pathway

“…In particular, it has been previously reported that IMPDH2 was the predominant isoform in neoplastic and replicating cells (5). Accumulating evidence has also suggested that IMPDH2 may be closely implicated in different types of malignancy (18)(19)(20)(21). In addition, it was revealed that IMPDH2 may be a useful biomarker for patient prognosis (20,21).…”