Abstract 153P
Background
Long non-coding RNAs (LncRNAs) widely involved in various processes in cancers. Exosomes are important elements in tumor microenvironment, and usually transmit miRNAs or LncRNAs in cancer cells. Rapid progression of residual hepatocellular carcinoma after insufficient radiofrequency ablation has been confirmed, however, the role of exosomes in the underlying mechanism has never been unmasked.
Methods
The expression of LINC00174 was modified in the Huh7 and Huh7-H cell lines respectively. Western blot was used to examine the level of the exosomal protein marker. Transwell assay and western blot were used to evaluate the migration function of the HCC cells. qRT-PCR and western blot were used to examine the expression of LINC00174 level in the exosomes derived from the modified HCC cells. Online UCSC and JASPAR were used to predict the LINC00174 transcription. ChIP and a luciferase reporter assay were used to validate the positive regulation of MYC on LINC00174 transcription.
Results
LINC00174 was upregulated in both the cells and exosomes of cells. LINC00174 affected HCC cell migration and EMT via ERK and JNK pathways. The changes of c-JUN and p-c-JUN level in HCC cells treated with exosomes containing different level of LINC00174. JASPAR revealed the binding motif of c-JUN protein on the promoter region of its targets. ChIP and luciferase reporter assay validated that c-JUN was a positive regulator of MYCBP transcription. Exosomal LINC00174 activated Ras-regulated ERK and JNK pathways to enhance c-JUN expression and phosphorylation, and therefore upregulated MYCBP to strengthen MYC transcriptional activity, finally resulting in accelerated HCC progression.
Conclusions
Exosomal LINC00174 facilitates EMT via ERK-JNK/c-JUN/MYCBP/c-MYC signaling, providing a new way for the HCC patients unfortunately received the insufficient RFA.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Zhe jiang Cancer Hospital.
Funding
National Natural Science Funds of China (Grant number: 81702371).
Disclosure
The author has declared no conflicts of interest.
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