微泡
ATG5型
自噬
外体
癌症研究
下调和上调
竞争性内源性RNA
核糖核酸
生物
环状RNA
小RNA
RNA干扰
肿瘤进展
细胞生物学
癌症
长非编码RNA
基因
细胞凋亡
生物化学
遗传学
作者
Xin Wang,Fenglin Dong,Yingqiao Wang,Honglong Wei,Tao Li,Jie Li
出处
期刊:Research Square - Research Square
日期:2023-03-09
被引量:1
标识
DOI:10.21203/rs.3.rs-2604940/v1
摘要
Abstract Exosomes contribute substantially to the communication between tumor cells and normal cells. Benefiting from the stable structure, circular RNAs (circRNAs) are believed to serve an important function in exosome-mediated intercellular communication. Here, we focused on circRNAs enriched in starvation-stressed hepatocytic exosomes and further investigated their function and mechanism in hepatocellular carcinoma (HCC) progression. Differentially expressed circRNAs in exosomes were identified by RNA sequencing, and circTGFBR2 was identified and chosen for further study. The molecular mechanism of circTGFBR2 in HCC was demonstrated by RNA pulldown, RIP, dual-luciferase reporter assays, rescue experiments and tumor xenograft assay both in vitro and vivo. We confirmed exosomes with enriched circTGFBR2 led to an upregulated resistance of HCC cells to starvation stress. Mechanistically, circTGFBR2 delivered into HCC cells via exosomes serves as a competing endogenous RNA by binding miR-205-5p to facilitate ATG5 expression and enhance autophagy in HCC cells, resulting in resistance to starvation. Thus, we revealed that circTGFBR2 is a novel tumor promoter circRNA in hepatocytic exosomes and promotes HCC progression by enhancing ATG5–mediated protective autophagy via the circTGFBR2/miR-205-5p/ATG5 axis, which may be a potential therapeutic target for HCC.
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