Identification of key genes in cleft lip with or without cleft palate regulated by miR-199a-5p

Chen, Gang; Li, Meng-Xue; Wang, Heng-Xue; Hong, Jia-Wei; Shen, Jun-Yu; Wang, Qi; Shi, Qiao-Mei; Ge, Xing; Zhang, Ding; Zhang, Jinpeng; Xu, Li‐Chun

doi:10.1016/j.ijporl.2018.06.005

Cited by 14 publications

(10 citation statements)

References 46 publications

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“…Recent studies show that miRs play important roles in craniofacial development ( Shin et al, 2012 ; Seelan et al, 2014 ; Warner et al, 2014 ; Mukhopadhyay et al, 2019 ); for example, administration of miR-23b and miR-133 duplex results in facial defects in zebrafish ( Ding et al, 2016 ). A bioinformatic study suggested that miR-199a-5p may be associated with CL/P through the modulation of transforming growth factor (TGF)-α expression ( Chen et al, 2018 ). miR-140-5p overexpression inhibits cell proliferation through the suppression of genes associated with CP, Fgf9 , and Pdgfra in MEPM cells ( Li et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid

Yoshioka

Mikami

Ramakrishnan

et al. 2021

Front. Cell Dev. Biol.

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Cleft lip with/without cleft palate (CL/P) is one of the most common congenital birth defects, showing the complexity of both genetic and environmental contributions [e.g., maternal exposure to alcohol, cigarette, and retinoic acid (RA)] in humans. Recent studies suggest that epigenetic factors, including microRNAs (miRs), are altered by various environmental factors. In this study, to investigate whether and how miRs are involved in cleft palate (CP) induced by excessive intake of all-trans RA (atRA), we evaluated top 10 candidate miRs, which were selected through our bioinformatic analyses, in mouse embryonic palatal mesenchymal (MEPM) cells as well as in mouse embryos treated with atRA. Among them, overexpression of miR-27a-3p, miR-27b-3p, and miR-124-3p resulted in the significant reduction of cell proliferation in MEPM cells through the downregulation of CP-associated genes. Notably, we found that excessive atRA upregulated the expression of miR-124-3p, but not of miR-27a-3p and miR-27b-3p, in both in vivo and in vitro. Importantly, treatment with a specific inhibitor for miR-124-3p restored decreased cell proliferation through the normalization of target gene expression in atRA-treated MEPM cells and atRA-exposed mouse embryos, resulting in the rescue of CP in mice. Taken together, our results indicate that atRA causes CP through the induction of miR-124-3p in mice.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid

Yoshioka

Mikami

Ramakrishnan

et al. 2021

Front. Cell Dev. Biol.

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“…Constructing miRNA-mRNA networks is widely used to unveil the miRNA’s regulatory roles in diseases. Chen et al built the connection between 429 unknown target genes and extensively reported miRNA, miR-199a-5p (Chen et al, 2018). However, simplex methods led to certain bias of results and identify lots of DEGs without biological roles as well.…”

Section: Discussionmentioning

confidence: 99%

Distinct Expression of miR-378 in Nonsyndromic Cleft Lip and/or Cleft Palate: A Cogitation of Skewed Sex Ratio in Prevalence

Xie

Shi

et al. 2020

The Cleft Palate Craniofacial Journal

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Objective: Nonsyndromic cleft lip and/or cleft palate (NSCL/P) is an isolated phenotype of orofacial clefts with skewed sex ratio in prevalence. This study aims to identify differentially expressed genes (DEGs) and microRNAs (DEMs) of NSCL/P by integrated bioinformatics analysis, revealing mechanisms for sexual dimorphism in prevalence. Materials and Methods: First, we downloaded the expression profile data from Gene Expression Omnibus database to identify DEGs and DEMs. Second, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses performed DEGs’ functions. Then, clustered DEGs were identified through protein–protein interaction networks. Combining clustered DEGs with key genes searched in GeneCards enlarged NSCL/P-related genes. Moreover, the genes were linked by transcription factors (TFs). Subsequently, connected by the above TFs, DEMs and genes were used to establish the miRNA-TF-messenger RNA (mRNA) regulatory networks. Results: The DEGs in sex-ignored group, female-only group, and male-only group were obtained, respectively. Among the DEMs, miR-378 was downregulated in females but upregulated in males. In female-only group, the miRNA-TF-mRNA regulatory networks showed miR-378-SP1-POLE2/CDK6/EZR regulatory axis was found to be key candidates of NSCL/P. Conclusions: Our findings suggest that different expression of miR-378 is consistent with the skewed sex ratio in the prevalence of NSCL/P.

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“…Many different microRNAs have been identified to temporally and spatially regulate morphogens and transcription factors during palatogenesis (Eberhart et al, 2008;Seelan et al, 2014;Ding et al, 2016;Reiss and Bhakdi, 2017;Schoen et al, 2017). Not surprisingly, microRNAs have been suggested as be new targets for investigating in CL/P studies (Li et al, 2010;Wang et al, 2013Wang et al, , 2017Ma et al, 2014;Gao et al, 2015;Li D. et al, 2016;Li J. et al, 2016;Schoen et al, 2017Schoen et al, , 2018Chen et al, 2018;Grassia et al, 2018;Pan et al, 2018;Suzuki et al, 2018;Wu N. et al, 2018;Xu M. et al, 2018).…”

Section: Ecm Structural Molecules and Soluble Factorsmentioning

confidence: 99%

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

Paiva

Maas

Santos

et al. 2019

Front. Cell Dev. Biol.

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Craniofacial development comprises a complex process in humans in which failures or disturbances frequently lead to congenital anomalies. Cleft lip with/without palate (CL/P) is a common congenital anomaly that occurs due to variations in craniofacial development genes, and may occur as part of a syndrome, or more commonly in isolated forms (non-syndromic). The etiology of CL/P is multifactorial with genes, environmental factors, and their potential interactions contributing to the condition. Rehabilitation of CL/P patients requires a multidisciplinary team to perform the multiple surgical, dental, and psychological interventions required throughout the patient's life. Despite progress, lip/palatal reconstruction is still a major treatment challenge. Genetic mutations and polymorphisms in several genes, including extracellular matrix (ECM) genes, soluble factors, and enzymes responsible for ECM remodeling (e.g., metalloproteinases), have been suggested to play a role in the etiology of CL/P; hence, these may be considered likely targets for the development of new preventive and/or therapeutic strategies. In this context, investigations are being conducted on new therapeutic approaches based on tissue bioengineering, associating stem cells with biomaterials, signaling molecules, and innovative technologies. In this review, we discuss the role of genes involved in ECM composition and remodeling during secondary palate formation and pathogenesis and genetic etiology of CL/P. We also discuss potential therapeutic approaches using bioactive molecules and principles of tissue bioengineering for state-of-the-art CL/P repair and palatal reconstruction.

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Identification of key genes in cleft lip with or without cleft palate regulated by miR-199a-5p

Cited by 14 publications

References 46 publications

MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid

MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid

Distinct Expression of miR-378 in Nonsyndromic Cleft Lip and/or Cleft Palate: A Cogitation of Skewed Sex Ratio in Prevalence

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

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