Abstract
Abstract
Background
Gastric cancer (GC), as one of the most common malignancies across the globe, is the fourth leading cause of cancer-related deaths. Though a large body of research has been conducted to develop the therapeutic methods of GC, the survival rate of advanced patients is still poor. We aimed to dig into the potential regulatory mechanism of GC progression.
Methods
Bioinformatics tools and fundamental assays were performed at first to confirm the candidate genes in our study. The functional assays and mechanism experiments were conducted to verify the regulatory mechanisms of the genes underlying GC progression.
Results
Long non-coding RNA (lncRNA) SND1 intronic transcript 1 (SND1-IT1) is highly expressed in exosomes secreted by GC cells. SND1-IT1 was verified to bind to microRNA-1245b-5p (miR-1245b-5p) through competitive adsorption to promote ubiquitin specific protease 3 (USP3) messenger RNA (mRNA) expression. SND1-IT1 was validated to recruit DEAD-box helicase 54 (DDX54) to promote USP3 mRNA stability. SND1-IT1 induces malignant transformation of GES-1 cells through USP3. USP3 mediates the deubiquitination of snail family transcriptional repressor 1 (SNAIL1).
Conclusions
Exosome-mediated lncRNA SND1-IT1 from GC cells enhances malignant transformation of GES-1 cells via up-regulating SNAIL1.
Graphical Abstract
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
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