Phenytoin Inhibits Cell Proliferation Through MicroRNA-196a-5p in Mouse Lip Mesenchymal Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Feb 12

PMID 33572377

Citations 7

Authors

Hiroki Yoshioka

Sai Shankar Ramakrishnan

Akiko Suzuki

Junichi Iwata

Affiliations

Soon will be listed here.

Abstract

Cleft lip (CL) is one of the most common birth defects. It is caused by either genetic mutations or environmental factors. Recent studies suggest that environmental factors influence the expression of noncoding RNAs [e.g., microRNA (miRNA)], which can regulate the expression of genes crucial for cellular functions. In this study, we examined which miRNAs are associated with CL. Among 10 candidate miRNAs (miR-98-3p, miR-101a-3p, miR-101b-3p, miR-141-3p, miR-144-3p, miR-181a-5p, miR-196a-5p, miR-196b-5p, miR-200a-3p, and miR-710) identified through our bioinformatic analysis of CL-associated genes, overexpression of miR-181a-5p, miR-196a-5p, miR-196b-5p, and miR-710 inhibited cell proliferation through suppression of genes associated with CL in cultured mouse embryonic lip mesenchymal cells (MELM cells) and O9-1 cells, a mouse cranial neural crest cell line. In addition, we found that phenytoin, an inducer of CL, decreased cell proliferation through miR-196a-5p induction. Notably, treatment with a specific inhibitor for miR-196a-5p restored cell proliferation through normalization of expression of CL-associated genes in the cells treated with phenytoin. Taken together, our results suggest that phenytoin induces CL through miR-196a-5p induction, which suppresses the expression of CL-associated genes.

Citing Articles

LncRNA-NONMMUT100923.1 regulates mouse embryonic palatal shelf adhesion by sponging miR-200a-3p to modulate medial epithelial cell desmosome junction during palatogenesis.

Zhang M, Zhou J, Ji Y, Shu S, Zhang M, Liang Y Heliyon. 2023; 9(5):e16329.

PMID: 37251885 PMC: 10208945. DOI: 10.1016/j.heliyon.2023.e16329.

Mitochondrial Metabolism and EV Cargo of Endothelial Cells Is Affected in Presence of EVs Derived from MSCs on Which HIF Is Activated.

Zanotti F, Zanolla I, Trentini M, Tiengo E, Pusceddu T, Licastro D Int J Mol Sci. 2023; 24(6).

PMID: 36983075 PMC: 10055915. DOI: 10.3390/ijms24066002.

MicroRNAs and Gene Regulatory Networks Related to Cleft Lip and Palate.

Iwaya C, Suzuki A, Iwata J Int J Mol Sci. 2023; 24(4).

PMID: 36834963 PMC: 9958963. DOI: 10.3390/ijms24043552.

miR-23a-3p and miR-181a-5p modulate SNAP-25 expression.

Agostini S, Bolognesi E, Mancuso R, Marventano I, Citterio L, Guerini F PLoS One. 2023; 18(1):e0279961.

PMID: 36649268 PMC: 9844927. DOI: 10.1371/journal.pone.0279961.

Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Epilepsy and Their Interaction with Antiseizure Medications.

Tesiye M, Gol M, Fadardi M, Kani S, Costa A, Ghasemi-Kasman M Cells. 2022; 11(24).

PMID: 36552892 PMC: 9777461. DOI: 10.3390/cells11244129.

References

Candini O, Spano C, Murgia A, Grisendi G, Veronesi E, Piccinno M . Mesenchymal progenitors aging highlights a miR-196 switch targeting HOXB7 as master regulator of proliferation and osteogenesis. Stem Cells. 2014; 33(3):939-50. DOI: 10.1002/stem.1897. View

Rattanasopha S, Tongkobpetch S, Srichomthong C, Siriwan P, Suphapeetiporn K, Shotelersuk V . PDGFRa mutations in humans with isolated cleft palate. Eur J Hum Genet. 2012; 20(10):1058-62. PMC: 3449079. DOI: 10.1038/ejhg.2012.55. View

Nie X, Wang Q, Jiao K . Dicer activity in neural crest cells is essential for craniofacial organogenesis and pharyngeal arch artery morphogenesis. Mech Dev. 2011; 128(3-4):200-7. PMC: 4130178. DOI: 10.1016/j.mod.2010.12.002. View

Hegde A, Kaur A, Sood A, Dhanorkar M, Varma H, Singh G . Fetal Hydantoin Syndrome. J Pediatr. 2017; 188:304. DOI: 10.1016/j.jpeds.2017.05.018. View

Ries R, Yu W, Holton N, Cao H, Amendt B . Inhibition of the miR-17-92 Cluster Separates Stages of Palatogenesis. J Dent Res. 2017; 96(11):1257-1264. PMC: 5613877. DOI: 10.1177/0022034517716915. View

Nakatomi M, Ludwig K, Knapp M, Kist R, Lisgo S, Ohshima H . deficiency interacts with hypoxia and induces a morphogenetic regulation during mouse lip development. Development. 2020; 147(21). DOI: 10.1242/dev.189175. View

Wang S, Sun C, Meng Y, Zhang B, Wang X, Su Y . A pilot study: Screening target miRNAs in tissue of nonsyndromic cleft lip with or without cleft palate. Exp Ther Med. 2017; 13(5):2570-2576. PMC: 5443217. DOI: 10.3892/etm.2017.4248. View

Li L, Meng T, Jia Z, Zhu G, Shi B . Single nucleotide polymorphism associated with nonsyndromic cleft palate influences the processing of miR-140. Am J Med Genet A. 2010; 152A(4):856-62. DOI: 10.1002/ajmg.a.33236. View

Couly G, Grapin-Botton A, Coltey P, Ruhin B, Le Douarin N . Determination of the identity of the derivatives of the cephalic neural crest: incompatibility between Hox gene expression and lower jaw development. Development. 1998; 125(17):3445-59. DOI: 10.1242/dev.125.17.3445. View

10.

Lin H, Guo S, Dutcher S . RPGRIP1L helps to establish the ciliary gate for entry of proteins. J Cell Sci. 2018; 131(20). PMC: 6215392. DOI: 10.1242/jcs.220905. View

11.

Hornstein E, Mansfield J, Yekta S, Hu J, Harfe B, McManus M . The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature. 2005; 438(7068):671-4. DOI: 10.1038/nature04138. View

12.

Naguibneva I, Ameyar-Zazoua M, Polesskaya A, Ait-Si-Ali S, Groisman R, Souidi M . The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol. 2006; 8(3):278-84. DOI: 10.1038/ncb1373. View

13.

Barritt L, Miller J, Scheetz L, Gardner K, Pierce M, Soukup G . Conditional deletion of the human ortholog gene Dicer1 in Pax2-Cre expression domain impairs orofacial development. Indian J Hum Genet. 2013; 18(3):310-9. PMC: 3656520. DOI: 10.4103/0971-6866.107984. View

14.

Millicovsky G, Johnston M . Maternal hyperoxia greatly reduces the incidence of phenytoin-induced cleft lip and palate in A/J mice. Science. 1981; 212(4495):671-2. DOI: 10.1126/science.7221553. View

15.

Wu N, Yan J, Han T, Zou J, Shen W . Integrated assessment of differentially expressed plasma microRNAs in subtypes of nonsyndromic orofacial clefts. Medicine (Baltimore). 2018; 97(25):e11224. PMC: 6023672. DOI: 10.1097/MD.0000000000011224. View

16.

Li L, Zhu G, Meng T, Shi J, Wu J, Xu X . Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate. Am J Med Genet A. 2011; 155A(12):2940-8. DOI: 10.1002/ajmg.a.34254. View

17.

Li D, Zhang H, Ma L, Han Y, Xu M, Wang Z . Associations between microRNA binding site SNPs in FGFs and FGFRs and the risk of non-syndromic orofacial cleft. Sci Rep. 2016; 6:31054. PMC: 4980626. DOI: 10.1038/srep31054. View

18.

Moens C, Selleri L . Hox cofactors in vertebrate development. Dev Biol. 2006; 291(2):193-206. DOI: 10.1016/j.ydbio.2005.10.032. View

19.

Goldman A, Baker M, Piddington R, Herold R . Inhibition of programmed cell death in mouse embryonic palate in vitro by cortisol and phenytoin: receptor involvement and requirement of protein synthesis. Proc Soc Exp Biol Med. 1983; 174(2):239-43. DOI: 10.3181/00379727-174-41731. View

20.

Balaraman S, Schafer J, Tseng A, Wertelecki W, Yevtushok L, Zymak-Zakutnya N . Plasma miRNA Profiles in Pregnant Women Predict Infant Outcomes following Prenatal Alcohol Exposure. PLoS One. 2016; 11(11):e0165081. PMC: 5102408. DOI: 10.1371/journal.pone.0165081. View