Abstract：
BACKGROUND:As an important means of communication, exosomes play an important role in the development of hepatocellular carcinoma (HCC). METHODS:Bioinformatics analysis, dual-luciferase reporter assays, methylation-specific quantitative PCR, and ChIP-PCR analysis were used to gain insight into the underlying mechanism of miR-21 in HCC. RESULTS:The detection of miRNAs in exosomes of HCC showed that miR-21 expression in exosomes was positively correlated with the expression level of miR-21 in cells and negatively correlated with the expression of its target genes PTEN, PTENp1 and TETs. HCC cell-derived exosomes could increase miR-21 and p-Akt expression in HCC cells and downregulate the expression of PTEN, PTENp1 and TETs. MiR-21 inhibitors or PTENp1 overexpression vectors could weaken the effect of the abovementioned exosomes and simultaneously weaken their role in promoting cell proliferation and migration and inhibiting apoptosis. Further studies showed that miR-21 not only directly regulated the expression of PTEN, PTENp1 and TETs but also increased the methylation level of the PTENp1 promoter by regulating the expression of TETs, thereby inhibiting the expression of PTENp1 and further downregulating the expression of PTEN. CONCLUSIONS:Exosomal miR-21 can regulate the expression of the tumor suppressor genes PTEN and PTENp1 in various ways and affect the growth of HCC cells.
journal_name
Mol Cancerjournal_title
Molecular cancerauthors
Cao LQ,Yang XW,Chen YB,Zhang DW,Jiang XF,Xue Pdoi
10.1186/s12943-019-1075-2subject
Has Abstractpub_date
2019-10-27 00:00:00pages
148issue
1issn
1476-4598pii
10.1186/s12943-019-1075-2journal_volume
18pub_type
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