Unveiling dysregulated lncRNAs and networks in non-syndromic cleft lip with or without cleft palate pathogenesis

• Published in: Scientific reports 2024-01, Vol.14 (1), p.1047-1047, Article 1047
• Main Authors: Wu, Caihong, Liu, Haojie, Zhan, Zhuorong, Zhang, Xinyu, Zhang, Mengnan, You, Jiawen, Ma, Junqing
• Format: Article
• Language: English
• Subjects: 631/114; 631/136; 631/208; Birth defects; Cleft lip/palate; Gene expression; Humanities and Social Sciences; Molecular modelling; multidisciplinary; Non-coding RNA; Pathogenesis; RNA-binding protein; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-51747-8

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital facial malformation with a complex, incompletely understood origin. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression, potentially shedding light on NSCL/P's etiology. This study aimed to identify critical lncRNAs and construct regulatory networks to unveil NSCL/P's underlying molecular mechanisms. Integrating gene expression profiles from the Gene Expression Omnibus (GEO) database, we pinpointed 30 dysregulated NSCL/P-associated lncRNAs. Subsequent analyses enabled the creation of competing endogenous RNA (ceRNA) networks, lncRNA-RNA binding protein (RBP) interaction networks, and lncRNA cis and trans regulation networks. RT-qPCR was used to examine the regulatory networks of lncRNA in vivo and in vitro. Furthermore, protein levels of lncRNA target genes were validated in human NSCL/P tissue samples and murine palatal shelves. Consequently, two lncRNAs and three mRNAs: FENDRR (log2FC = − 0.671, P = 0.040), TPT1-AS1 (log2FC = 0.854, P = 0.003), EIF3H (log2FC = − 1.081, P = 0.041), RBBP6 (log2FC = 0.914, P = 0.037), and SRSF1 (log2FC = 0.763, P = 0.026) emerged as potential contributors to NSCL/P pathogenesis. Functional enrichment analyses illuminated the biological functions and pathways associated with these lncRNA-related networks in NSCL/P. In summary, this study comprehensively delineates the dysregulated transcriptional landscape, identifies associated lncRNAs, and reveals pivotal sub-networks relevant to NSCL/P development, aiding our understanding of its molecular progression and setting the stage for further exploration of lncRNA and mRNA regulation in NSCL/P.