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Background: Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium‐binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article. Methods: The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT‐PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual‐luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit‐8 (CCK‐8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E‐cadherin expression, and a western blot was used to detect the expression of MMP‐2, MMP‐9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α‐KG, and glutamate. Results: S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis. Conclusion: In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment. [ABSTRACT FROM AUTHOR]

Aims: Dozens of causative genes and their mechanisms of nonsyndromic cleft lip with or without cleft palate (NSCL/P) were revealed through genome‐wide association and linkage studies. Results were, however, not always replicated in different populations or methodologies. This study used case–control and family based approaches to investigate the etiology of NSCL/P and its two subtypes: nonsyndromic cleft lip only (NSCLO) and nonsyndromic cleft lip and palate (NSCLP) among the Vietnamese population. Methods: Two hundred and seventeen NSCL/P case‐parent trios (one affected child and two parents), including 105 NSCLO and 112 NSCLP were involved for a family based design; and 273 ethnic and region‐matched healthy controls with no cleft history in their families were recruited for a case–control design. Three SNPs consisting of TFAP2A (rs1675414 and rs303048) and 8q24 (rs987525) were genotyped using the TaqMan SNP genotyping assay. Results: TFAP2A rs1675414 was associated with NSCLO, replicated by both case‐control and family based tests. Other SNPs yielded no evidence of susceptibility to NSCL/P or two subtypes. Conclusion: The current investigation suggests an intriguing role of TFAP2A in the etiology of NSCLO among the Vietnamese population. This study used case‐control and family‐based approaches to investigate the etiology of NSCL/P and its two subtypes: nonsyndromic cleft lip only (NSCLO), nonsyndromic cleft lip and palate (NSCLP) among Vietnamese population. TFAP2A rs1675414 was associated with NSCLO, replicated by both case‐control and family‐based tests. [ABSTRACT FROM AUTHOR]

MITF governs multiple steps in the development of melanocytes, including specification from neural crest, growth, survival, and terminal differentiation. In addition, the level of MITF activity determines the phenotype adopted by melanoma cells, whether invasive, proliferative, or differentiated. However, MITF does not act alone. Here, we review literature on the transcription factors that co-regulate MITF-dependent genes. Ch IP-seq studies have indicated that the transcription factors SOX10, YY1, and TFAP2A co-occupy subsets of regulatory elements bound by MITF in melanocytes. Analyses at single loci also support roles for LEF1, RB1, IRF4, and PAX3 acting in combination with MITF, while sequence motif analyses suggest that additional transcription factors colocalize with MITF at many melanocyte-specific regulatory elements. However, the precise biochemical functions of each of these MITF collaborators and their contributions to gene expression remain to be elucidated. Analogous to the transcriptional networks in morphogen-patterned tissues during embryogenesis, we anticipate that the level of MITF activity is controlled not only by the concentration of activated MITF, but also by additional transcription factors that either quantitatively or qualitatively influence the expression of MITF-target genes. [ABSTRACT FROM AUTHOR]

Background Single genetic variants can affect multiple tissues during development. Thus it is possible that disruption of shared gene regulatory networks might underlie syndromic presentations. In this study, we explore this idea through examination of two critical developmental programs that control orofacial and neural tube development and identify shared regulatory factors and networks. Identification of these networks has the potential to yield additional candidate genes for poorly understood developmental disorders and assist in modeling and perhaps managing risk factors to prevent morbidly and mortality. Methods We reviewed the literature to identify genes common between orofacial and neural tube defects and development. We then conducted a bioinformatic analysis to identify shared molecular targets and pathways in the development of these tissues. Finally, we examine publicly available RNA-Seq data to identify which of these genes are expressed in both tissues during development. Results We identify common regulatory factors in orofacial and neural tube development. Pathway enrichment analysis shows that folate, cancer and hedgehog signaling pathways are shared in neural tube and orofacial development. Developing neural tissues differentially express mouse exencephaly and cleft palate genes, whereas developing orofacial tissues were enriched for both clefting and neural tube defect genes. Conclusion These data suggest that key developmental factors and pathways are shared between orofacial and neural tube defects. We conclude that it might be most beneficial to focus on common regulatory factors and pathways to better understand pathology and develop preventative measures for these birth defects. Birth Defects Research 109:169-179, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Orofacial clefting is a common birth defect with significant morbidity. A panoply of candidate genes have been discovered through synergy of animal models and human genetics. Among these, variants in interferon regulatory factor 6 ( IRF6) cause syndromic orofacial clefting and contribute risk toward isolated cleft lip and palate (1/700 live births). Rare variants in IRF6 can lead to Van der Woude syndrome (1/35,000 live births) and popliteal pterygium syndrome (1/300,000 live births). Furthermore, IRF6 regulates GRHL3 and rare variants in this downstream target can also lead to Van der Woude syndrome. In addition, a common variant (rs642961) in the IRF6 locus is found in 30% of the world's population and contributes risk for isolated orofacial clefting. Biochemical studies revealed that rs642961 abrogates one of four AP-2alpha binding sites. Like IRF6 and GRHL3, rare variants in TFAP2A can also lead to syndromic orofacial clefting with lip pits (branchio-oculo-facial syndrome). The literature suggests that AP-2alpha, IRF6 and GRHL3 are part of a pathway that is essential for lip and palate development. In addition to updating the pathways, players and pursuits, this review will highlight some of the current questions in the study of orofacial clefting. Developmental Dynamics 245:220-232, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is a common pregnancy‐related syndrome characterized by hypertension and proteinuria, and a major cause of maternal mortality. Therefore, there is an urgent need to identify early biomarkers of PE. The aim of the present study was to identify the functions of miR‐576‐5p in PE. Methods: Effects of miR‐576‐5p and transcription factor AP‐2α (TFAP2A) on invasion of human trophoblast HTR8/SVneo cells were investigated. Real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blotting were used to assess the expression of miR‐576‐5p, TFAP2A, E‐cad, and Vimentin in PE tissues and cells. Additionally, immunofluorescence was used to detect the expression of TFAP2A in PE trophoblastic tissue. Subsequently, constructed miR‐576‐5p mimics, miR‐576‐5p inhibitor, and siRNA‐TFAP2A plasmids were transfected into HTR8/SVneo cells for further experiments, including a CCK‐8 assay for cell proliferation, Transwell assay for cell invasion and the luciferase reporter gene system was employed for target verification. Results: A lower expression of miR‐576‐5p and a higher expression of TFAP2A were identified in PE rats. E‐cadherin was highly expressed while Vimentin was downregulated. Further statistical analysis indicated that cell proliferation of HTR8/SVneo cells decreased in the miR‐576‐5p inhibitor group and increased in the miR‐576‐5p mimics and siRNA‐TFAP2A groups. miR‐576‐5p inhibitor suppressed cell invasion, and miR‐576‐5p mimics and siRNA‐TFAP2A improved cell invasion. The analysis of luciferase reporter demonstrated a decreased luciferase activity in miR‐576‐5p mimics group compared with control group, which indicates that TFAP2A may be a target of miR‐576‐5p. Interference of TFAP2A could downregulate E‐cadherin and upregulate Vimentin expression. Conclusion: Overexpression of miR‐576‐5p and knockdown of TFAP2A may elevate cell proliferation and invasion of human trophoblast cells in vitro. Therefore, miR‐576‐5p may be used as a notable biomarker for the diagnosis, prevention, and treatment of PE. miR‐576‐5p targeting TFAP2A deserve further investigation in order to explore their potential role in PE. [ABSTRACT FROM AUTHOR]