Abstract
Gastric cancer (GC) is one of the most common malignant tumors all over the world. And recurrence and metastasis are still the main causes of low survival rate for advanced GC. USP1 has been shown overexpressed in multiple cancers, which indicate its important biomarker in tumorigenesis and development. Our study is aimed at defining the exact role of USP1 on GC metastasis and the underlying mechanism. USP1 was firstly found overexpressed in GC tissues and relatively high-expression levels conferred poor survival rates. Then, real-time cellular analysis (RTCA) showed that USP1 knockdown inhibited GC metastasis both in vitro and in vivo. Mechanically, we demonstrated that USP1 promoted GC metastasis via upregulating ID2 expression and further confirmed that USP1 stabilized ID2 expression through deubiquitinating ID2 in GC. In conclusion, our study showed that USP1 promoted GC metastasis via stabilizing ID2 expression, which provides a potential biomarker and therapy target for GC.
Highlights
Gastric cancer (GC) is one of the most common malignant tumors all over the world, with estimated 951,600 new cases and 723,100 deaths occurring in 2012 [1]
The results showed that more intensive USP1 staining was found in GC tissues than that in adjacent normal tissues (Figure 2(c))
USP1 is a member of ubiquitin-specific protease (USP) which consists of 785 amino acids with a speculated molecular mass of 88.2 kDa [32]
Summary
Gastric cancer (GC) is one of the most common malignant tumors all over the world, with estimated 951,600 new cases and 723,100 deaths occurring in 2012 [1]. Endoscopic submucosal dissection or surgical resection of stomach is still the best choice for early GC, but for advanced patients, even with maximal treatments, the overall survival rates for 5 years are still low owing to recurrence and metastasis [5]. Molecular target treatment has shown its advantages in improving the prognosis of advanced GC patients in recent years [6]. Ubiquitination is an important posttranscriptional modification (PTM) which participate in a number of cellular processes, such as protein degradation, gene expression, and DNA repair [7]. Previous studies have shown that USP1 is overexpressed in multiple cancers, such as osteosarcoma, multiple myeloma, glioblastoma, and non-small-cell lung cancer (NSCLC) [16,17,18,19]. In the research of Zhiqiang et al, low expression of USP1 was found in non-small-cell lung
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