Exosome-mediated lncRNA SND1-IT1 from gastric cancer cells enhances malignant transformation of gastric mucosa cells via up-regulating SNAIL1.
Exosome-mediated lncRNA SND1-IT1 from gastric cancer cells enhances malignant transformation of gastric mucosa cells via up-regulating SNAIL1.
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DOI：
10.1186/s12967-022-03306-w
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发表时间：
2022-06-23
影响因子：
7.4
通讯作者：
Shi, Yang
中科院分区：
文献类型：
--
作者：
Jin, Guohua;Zhang, Jianguang;Cao, Tingting;Chen, Bang;Tian, Yu;Shi, Yang
胃癌是全球最常见的恶性肿瘤之一，是导致癌症相关死亡的第四大原因。虽然人们对GC的治疗方法进行了大量的研究，但晚期患者的存活率仍然很低。我们的目标是深入挖掘GC进展的潜在调控机制。首先通过生物信息学工具和基础分析来确定我们研究中的候选基因。通过功能分析和机制实验验证了胃癌进展相关基因的调控机制。长非编码RNA(Long Non-Coding RNA，LncRNA)SND1内含子转录本1(SND1-IT1)在GC细胞分泌的外体中高表达。SND1-IT1通过竞争吸附与microRNA-1245b-5p(miR-1245b-5p)结合，促进泛素特异性蛋白酶3(USP3)信使RNA(MRNA)的表达。SND1-IT1被证实可以招募DEAD-box Helicase 54(DDX54)来促进USP3mRNA的稳定性。SND1-IT1通过USP3诱导GES-1细胞恶性转化USP3介导蜗牛家族转录抑制因子1(SNAIL1)的去泛素化。来自GC细胞的Exosome介导的LncRNA SND1-IT1通过上调SNAIL1促进GES-1细胞的恶性转化。网上版载有补充材料，可在10.1186/s12967-022-03306-w查阅。
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. 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. 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). Exosome-mediated lncRNA SND1-IT1 from GC cells enhances malignant transformation of GES-1 cells via up-regulating SNAIL1. The online version contains supplementary material available at 10.1186/s12967-022-03306-w.
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