XCI-escaping gene KDM5C contributes to ovarian development via downregulating miR-320a
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Abstract
Mechanisms underlying female gonadal dysgenesis remain unclarified and relatively unstudied. Whether X-chromosome inactivation (XCI)-escaping genes and microRNAs (miRNAs) contribute to this condition is currently unknown. We compared 45,X Turner Syndrome women with 46,XX normal women, and investigated differentially expressed miRNAs in Turner Syndrome through plasma miRNA sequencing. We found that miR-320a was consistently upregulated not only in 45,X plasma and peripheral blood mononuclear cells (PBMCs), but also in 45,X fetal gonadal tissues. The levels of miR-320a in PBMCs from 45,X, 46,XX, 46,XY, and 47,XXY human subjects were inversely related to the expression levels of XCI-escaping gene KDM5C in PBMCs. In vitro models indicated that KDM5C suppressed miR-320a transcription by directly binding to the promoter of miR-320a to prevent histone methylation. In addition, we demonstrated that KITLG, an essential gene for ovarian development and primordial germ cell survival, was a direct target of miR-320a and that it was downregulated in 45,X fetal gonadal tissues. In conclusion, we demonstrated that downregulation of miR-320a by the XCI-escaping gene KDM5C contributed to ovarian development by targeting KITLG.
Keywords
Ingenuity Pathway Analysis Turner Syndrome Ovarian Development Primordial Follicle Gonadal Dysgenesis
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Abbreviations
- miRNA
microRNA
- TS
Turner syndrome
- PBMCs
Peripheral blood mononuclear cells
- XCI
X-chromosome inactivation
- H3K4me3
H3-tri-methylated K4
Notes
Acknowledgements
This work is supported by the National Basic Research Program of China (No. 2013CB967404 to H. F. H), the National Natural Science Foundation of China (No. 81490742 and 31471405 to H. F. H, No. 81401219 to J. Y. Z.), the NSFC-CIHR Joint Health Research Program (No. 8161101434 to H. F. H., No. 81361128007 to J. Z. S.), the Shanghai Municipal Commission of Science and Technology Program (No. 14DJ1400100 to H. F. H., No. 15411966700 to J. Y. Z.), and the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1184 to H. F. H). We thank LetPub (http://www.letpub.com) for its linguistic assistance during the preparation of this manuscript.
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Conflictof interest
The authors have declared no conflicts of interest.
Supplementary material
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