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IGF2BP2-modified circular RNA circCHD7 promotes endometrial cancer progression via stabilizing PDGFRB and activating JAK/STAT signaling pathway.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 2024 Aug; Vol. 31 (8), pp. 1221-1236. Date of Electronic Publication: 2024 May 22. - Publication Year :
- 2024
-
Abstract
- Circular RNAs (circRNAs) represent a class of covalently closed, single-stranded RNAs and have been linked to cancer progression. N6-methyladenosine (m <superscript>6</superscript> A) methylation is a ubiquitous RNA modification in cancer cells. Increasing evidence suggests that m <superscript>6</superscript> A can mediate the effects of circRNAs in cancer biology. In contrast, the post-transcriptional systems of m <superscript>6</superscript> A and circRNA in the progression of endometrial cancer (EC) remain obscure. The current study identified a novel circRNA with m <superscript>6</superscript> A modification, hsa&#95;circ&#95;0084582 (circCHD7), which was upregulated in EC tissues. Functionally, circCHD7 was found to promote the proliferation of EC cells. Mechanistically, circCHD7 interacted with insulin-like growth factor 2 mRNA-binding protein (IGF2BP2) to amplify its enrichment. Moreover, circCHD7 increased the mRNA stability of platelet-derived growth factor receptor beta (PDGFRB) in an m <superscript>6</superscript> A-dependent manner, thereby enhancing its expression. In addition, the circCHD7/IGF2BP2/PDGFRB axis activated the JAK/STAT signaling pathway and promoted EC cell proliferation. In conclusion, these findings provide new insights into the regulation of circRNA-mediated m <superscript>6</superscript> A modification, and the new "circCHD7-PDGFRB" model of regulation offers new perspectives on circCHD7 as a potential target for EC therapy.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Female
Mice
Receptor, Platelet-Derived Growth Factor beta genetics
Receptor, Platelet-Derived Growth Factor beta metabolism
Animals
Cell Proliferation genetics
STAT Transcription Factors metabolism
STAT Transcription Factors genetics
Janus Kinases metabolism
Janus Kinases genetics
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
RNA, Circular genetics
RNA, Circular metabolism
RNA-Binding Proteins genetics
RNA-Binding Proteins metabolism
Endometrial Neoplasms genetics
Endometrial Neoplasms pathology
Endometrial Neoplasms metabolism
Signal Transduction
Disease Progression
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5500
- Volume :
- 31
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 38778089
- Full Text :
- https://doi.org/10.1038/s41417-024-00781-9