Variants in MiRNA Regulome and Their Association with the Risk of Nonsyndromic Orofacial Clefts

Abstract

Aim: To investigate the associations between single nucleotide polymorphisms (SNPs) in miRNA regulome and nonsyndromic orofacial clefts. Materials & methods: The associations were evaluated by logistic regression model in stage I (504 cases and 455 controls) and stage II (1500 cases and 1386 controls). Functional experiments including luciferase activity assay, cell apoptosis and proliferation, serum miRNA expression, and mouse embryo RNA sequencing were performed. Results: Rs3830766 in the enhancer of hsa-miR-4260 was associated with cleft lip only (CLO) and enhancer activity. Hsa-miR-4260 expression decreased in the serum of CLO. Overexpression of miR-4260 inhibited cell proliferation and promoted cell apoptosis. UBB was the target gene of hsa-miR-4260. Conclusion: Rs3830766 in the hsa-miR-4260 enhancer that can interact with UBB was relevant to CLO.

Keywords::

• CLO
• miRNA regulome
• NSOFC
• SNPs

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0124

Acknowledgments

We thank all the participants, research staff and students who contributed to this study. We thank Wiley Editing Services (https://wileyeditingservices.com/cn/) for providing the English writing assistance.

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (81830031, 81970969, 81570959), the State Key Lab of Reproductive Medicine of Nanjing Medical University (JX116GSP20171416), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD-2018-87), the Natural Science Foundation of Jiangsu Province (BL2014073 and 15KJA320002 to L Wang), the Qing Lan Project (Y Pan), Six Distinguished Talent (2016-WSW-008) and Jiangsu Provincial Medical Talent (ZDRCC2016023 Y Pan), the Jiangsu Provincial Key Medical Discipline (zdxka2016026), the Natural Science Foundation of Jiangsu Province (BK20180667 to D Li), and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (18KJB320011). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript and funded by the National Natural Science Foundation of China (81570959).

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81830031, 81970969, 81570959), the State Key Lab of Reproductive Medicine of Nanjing Medical University (JX116GSP20171416), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD-2018-87), the Natural Science Foundation of Jiangsu Province (BL2014073 and 15KJA320002 to L Wang), the Qing Lan Project (Y Pan), Six Distinguished Talent (2016-WSW-008) and Jiangsu Provincial Medical Talent (ZDRCC2016023 Y Pan), the Jiangsu Provincial Key Medical Discipline (zdxka2016026), the Natural Science Foundation of Jiangsu Province (BK20180667 to D Li), and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (18KJB320011). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.