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Antifibrotic Potential of MiR-335-3p in Hereditary Gingival Fibromatosis.
J Dent Res 2019; 98(10):1140-1149JD

Abstract

Hereditary gingival fibromatosis (HGF) is a highly genetically heterogeneous disease, and current therapeutic method is limited to surgical resection with a high recurrence rate. MicroRNAs (miRNAs) are able to fine-tune large-scale target genes. Here we established a simple but effective computational strategy based on available miRNA target prediction algorithms to pinpoint the most potent miRNA that could negatively regulate a group of functional genes. Based on this rationale, miR-335-3p was top ranked by putatively targeting 85 verified profibrotic genes and 79 upregulated genes in HGF patients. Experimentally, downregulation of miR-355-3p was demonstrated in HGF-derived gingival fibroblasts as well as in transforming growth factor β-stimulated normal human gingival fibroblasts (NHGFs) compared to normal control. Ectopic miR-335-3p attenuated, whereas knockdown of miR-335-3p promoted, the fibrogenic activity of human gingival fibroblasts. Mechanically, miR-335-3p directly targeted SOS1, SMAD2/3, and CTNNB1 by canonical and noncanonical base paring. In particular, different portfolios of fibrotic markers were suppressed by silencing SOS1, SMAD2/3, or CTNNB1, respectively. Thus, our study first proposes a novel miRNA screening approach targeting a functionally related gene set and identifies miR-335-3p as a novel target for HGF treatment. Mechanically, miR-335-3p suppresses the fibrogenic activity of human gingival fibroblasts by repressing multiple core molecules in profibrotic networks. Our strategy provides a new paradigm in the treatment for HGF as well as other diseases.

Authors+Show Affiliations

1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31323181

Citation

Gao, Q, et al. "Antifibrotic Potential of MiR-335-3p in Hereditary Gingival Fibromatosis." Journal of Dental Research, vol. 98, no. 10, 2019, pp. 1140-1149.
Gao Q, Yang K, Chen D, et al. Antifibrotic Potential of MiR-335-3p in Hereditary Gingival Fibromatosis. J Dent Res. 2019;98(10):1140-1149.
Gao, Q., Yang, K., Chen, D., Song, Y., Qiao, W., Sun, X., ... Bian, Z. (2019). Antifibrotic Potential of MiR-335-3p in Hereditary Gingival Fibromatosis. Journal of Dental Research, 98(10), pp. 1140-1149. doi:10.1177/0022034519863300.
Gao Q, et al. Antifibrotic Potential of MiR-335-3p in Hereditary Gingival Fibromatosis. J Dent Res. 2019;98(10):1140-1149. PubMed PMID: 31323181.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antifibrotic Potential of MiR-335-3p in Hereditary Gingival Fibromatosis. AU - Gao,Q, AU - Yang,K, AU - Chen,D, AU - Song,Y, AU - Qiao,W, AU - Sun,X, AU - Meng,L, AU - Bian,Z, Y1 - 2019/07/19/ PY - 2019/7/20/pubmed PY - 2019/7/20/medline PY - 2019/7/20/entrez KW - bioinformatics KW - extracellular matrix KW - fibrosis KW - gingiva KW - heterogeneity KW - microRNAs SP - 1140 EP - 1149 JF - Journal of dental research JO - J. Dent. Res. VL - 98 IS - 10 N2 - Hereditary gingival fibromatosis (HGF) is a highly genetically heterogeneous disease, and current therapeutic method is limited to surgical resection with a high recurrence rate. MicroRNAs (miRNAs) are able to fine-tune large-scale target genes. Here we established a simple but effective computational strategy based on available miRNA target prediction algorithms to pinpoint the most potent miRNA that could negatively regulate a group of functional genes. Based on this rationale, miR-335-3p was top ranked by putatively targeting 85 verified profibrotic genes and 79 upregulated genes in HGF patients. Experimentally, downregulation of miR-355-3p was demonstrated in HGF-derived gingival fibroblasts as well as in transforming growth factor β-stimulated normal human gingival fibroblasts (NHGFs) compared to normal control. Ectopic miR-335-3p attenuated, whereas knockdown of miR-335-3p promoted, the fibrogenic activity of human gingival fibroblasts. Mechanically, miR-335-3p directly targeted SOS1, SMAD2/3, and CTNNB1 by canonical and noncanonical base paring. In particular, different portfolios of fibrotic markers were suppressed by silencing SOS1, SMAD2/3, or CTNNB1, respectively. Thus, our study first proposes a novel miRNA screening approach targeting a functionally related gene set and identifies miR-335-3p as a novel target for HGF treatment. Mechanically, miR-335-3p suppresses the fibrogenic activity of human gingival fibroblasts by repressing multiple core molecules in profibrotic networks. Our strategy provides a new paradigm in the treatment for HGF as well as other diseases. SN - 1544-0591 UR - https://www.unboundmedicine.com/medline/citation/31323181/Antifibrotic_Potential_of_MiR-335-3p_in_Hereditary_Gingival_Fibromatosis L2 - http://journals.sagepub.com/doi/full/10.1177/0022034519863300?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -