Exosome-mediated lncRNA SND1-IT1 from gastric cancer cells enhances malignant transformation of gastric mucosa cells via up-regulating SNAIL1

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

Hypoxic Macrophage-derived Exosomes Mediate Colorectal Cancer Progression through Targeting the Hippo Signaling Pathway

“…The results suggested that HMDEs were enriched with 678 proteins and 40 proteins increased while 28 proteins decreased compared to NMDEs (Supplementary1). These results were different from those of the hypoxic tumor cell-derived exosomes which was reported to be identi ed 3710 proteins under 0.5% O 2 for 24h [8,29]. Two explanations might be responsible for the differences.…”

“…Gastric cancer cells-derived exosomes are enriched with elevated lncRNA SND1-IT1 which enhances the malignant transformation of GES-1 cells by up-regulating SNAIL1 [29]. In terms of the function of exosome-derived proteins, exosomes secreted by hypoxic tumor cells are rich in 3710 proteins that promote macrophages to polarize toward M2-type macrophages and thus participate in tumor progression [8].…”

Research Progress for Targeting Deubiquitinases in Gastric Cancers

“…Although the regulatory mechanisms of some GC-related DUBs remain to be discovered, non-coding RNAs have been reported to modulate the expression of DUBs, such as USP3 and CYLD, in GC ( Table 1 ). Intriguingly, three studies discovered that non-coding RNAs are also key mediators of interactions between GC cells and other cell types, including gastric mucosa cells, CAFs, and M2-polarized macrophages, and that USP3, USP7, and CYLD are linked to this process [ 24 , 27 , 76 ]. Furthermore, several infectious agents, cytokines, and antitumor agents also affect the expression of several DUBs, such as USP3, USP7, USP10, USP29, CYLD, and A20 [ 21 , 27 , 32 , 54 , 73 , 97 , 98 , 122 ] ( Table 1 ), which implicates unknown pro-cancer effects under certain circumstances.…”

“…Hsa_circ_0017639, a circular RNA, is increased in GC cell lines and promotes proliferation and migration by increasing USP3 expression by sponging miR-224-5p [ 23 ]. In addition, Jin et al demonstrated that exosomal lncRNA SND1-IT1 secreted from GC cells not only recruited DDX54, a DEAD-box RNA helicase that binds to specific RNAs, to enhance USP3 mRNA stability, but also bound to miR-1245b-5p to upregulate USP3 expression, thus leading to SNAIL1 stabilization and inducing the malignant transformation of gastric mucosa cells [ 24 ]. Taken together, these studies suggest that targeting USP3 may be a potential treatment for GC.…”

Nanotherapeutic approaches for delivery of long non-coding RNAs: an updated review with emphasis on cancer

“…By competitively adsorbing USP3 to miRNA-1245b-5p, SND1-IT1 induces malignant transformation of GES-1 cells. 134 3.1.3. Exosomes for delivery of lncRNAs in hepatocellular cancer.…”