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circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma.
- Source :
-
Cell death & disease [Cell Death Dis] 2018 Oct 25; Vol. 9 (11), pp. 1091. Date of Electronic Publication: 2018 Oct 25. - Publication Year :
- 2018
-
Abstract
- Some types of circular RNA (circRNA) are aberrantly expressed in human diseases including hepatocellular carcinoma (HCC). However, its regulation mechanism and diagnostic roles are largely unknown. Here, we identified that circRNA&#95;104075 (circ&#95;104075) was highly expressed in HCC tissues, cell lines and serum. Mechanistically, HNF4a bound to the -1409 to -1401 region of the circ&#95;104075 promoter to stimulate the expression of circ&#95;104075. Moreover, circ&#95;104075 acted as a ceRNA to upregulate YAP expression by absorbing miR-582-3p. Interestingly, an N <superscript>6</superscript> -methyladenosine (m <superscript>6</superscript> A) motif was identified in the 353-357 region of YAP 3'UTR, and this m <superscript>6</superscript> A modification was essential for the interaction between miR-582-3p and YAP 3'UTR. Further, the diagnostic performance of circ&#95;104075 was evaluated. The area under the receiver operating characteristic (AUC-ROC) for circ&#95;104075 was 0.973 with a sensitivity of 96.0% and a specificity of 98.3%. Collectively, we determined that circ&#95;104075 was highly expressed in HCC and elucidated its upstream and downstream regulatory mechanisms. circ&#95;104075 additionally has the potential to serve as a new diagnostic biomarker in HCC. Targeting circ&#95;104075 may provide new strategies in HCC diagnosis and therapy.
- Subjects :
- Adenosine analogs & derivatives
Adenosine metabolism
Adult
Aged
Animals
Biomarkers, Tumor metabolism
Carcinoma, Hepatocellular blood
Cell Survival
Female
Hep G2 Cells
Hepatocyte Nuclear Factor 4 genetics
Humans
Liver Neoplasms blood
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs metabolism
Middle Aged
Promoter Regions, Genetic
Protein Interaction Domains and Motifs
ROC Curve
YAP-Signaling Proteins
Adaptor Proteins, Signal Transducing metabolism
Carcinogenesis metabolism
Carcinoma, Hepatocellular metabolism
Hepatocyte Nuclear Factor 4 metabolism
Liver Neoplasms metabolism
RNA, Circular metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 9
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 30361504
- Full Text :
- https://doi.org/10.1038/s41419-018-1132-6