PMID- 32169113 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20210618 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 11 IP - 1 DP - 2020 Mar 13 TI - Genome-wide identification of long noncoding RNAs and their competing endogenous RNA networks involved in the odontogenic differentiation of human dental pulp stem cells. PG - 114 LID - 10.1186/s13287-020-01622-w [doi] LID - 114 AB - BACKGROUND: Long noncoding RNAs (lncRNAs) play an important role in the multiple differentiations of mesenchymal stem cells (MSCs). However, few studies have focused on the regulatory mechanism of lncRNAs in the odontogenic differentiation of human dental pulp stem cells (hDPSCs). METHODS: hDPSCs were induced to differentiate into odontoblasts in vitro, and the expression profiles of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in differentiated and undifferentiated cells were obtained by microarray. Bioinformatics analyses including Gene Ontology (GO) analysis, pathway analysis, and binding site prediction were performed for functional annotation of lncRNA. miRNA/odontogenesis-related gene networks and lncRNA-associated ceRNA networks were constructed. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to verify the expression of selected genes. RNA fluorescence in situ hybridization (FISH), qRT-PCR, and western blot analysis were used to explore the location and function of lncRNA-G043225. Dual-luciferase reporter assay was performed to confirm the binding sites of miR-588 with G043225 and Fibrillin 1 (FBN1). RESULTS: We identified 132 lncRNAs, 114 miRNAs, and 172 mRNAs were differentially expressed. GO analysis demonstrated that regulation of the neurogenic locus notch homolog (Notch), Wnt, and epidermal growth factor receptor (ERBB) signaling pathways and activation of mitogen-activated protein kinase (MAPK) activity were related to odontogenic differentiation. Pathway analysis indicated that the most significant pathway was the forkhead box O (FoxO) signaling pathway, which is related to odontogenic differentiation. Two odontogenesis-related gene-centered lncRNA-associated ceRNA networks were successfully constructed. The qRT-PCR validation results were consistent with the microarray analysis. G043225 mainly locating in cytoplasm was proved to promote the odontogenic differentiation of hDPSCs via miR-588 and FBN1. CONCLUSION: This is the first study revealing lncRNA-associated ceRNA network during odontogenic differentiation of hDPSCs using microarray, and it could provide clues to explore the mechanism of action at the RNA-RNA level as well as novel treatments for dentin regeneration based on stem cells. FAU - Chen, Zhao AU - Chen Z AD - Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. FAU - Zhang, Kaiying AU - Zhang K AD - Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. FAU - Qiu, Wei AU - Qiu W AD - Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. FAU - Luo, Yifei AU - Luo Y AD - Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. FAU - Pan, Yuhua AU - Pan Y AD - Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. FAU - Li, Jianjia AU - Li J AD - Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. FAU - Yang, Yeqing AU - Yang Y AD - Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. FAU - Wu, Buling AU - Wu B AD - Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. bulingwu@smu.edu.cn. AD - College of Stomatology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. bulingwu@smu.edu.cn. FAU - Fang, Fuchun AU - Fang F AD - Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. fangfuchun520@163.com. AD - College of Stomatology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. fangfuchun520@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200313 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (MIRN588 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) SB - IM MH - Cell Differentiation MH - Dental Pulp MH - Gene Regulatory Networks MH - Humans MH - In Situ Hybridization, Fluorescence MH - *MicroRNAs/genetics MH - Odontogenesis MH - *RNA, Long Noncoding/genetics MH - Stem Cells PMC - PMC7071724 OTO - NOTNLM OT - Competing endogenous RNA OT - Human dental pulp stem cells OT - Long noncoding RNA OT - MicroRNA OT - Odontogenic differentiation COIS- The authors declare that they have no competing interests. EDAT- 2020/03/15 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/03/13 CRDT- 2020/03/15 06:00 PHST- 2019/10/03 00:00 [received] PHST- 2020/02/26 00:00 [accepted] PHST- 2020/02/03 00:00 [revised] PHST- 2020/03/15 06:00 [entrez] PHST- 2020/03/15 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/03/13 00:00 [pmc-release] AID - 10.1186/s13287-020-01622-w [pii] AID - 1622 [pii] AID - 10.1186/s13287-020-01622-w [doi] PST - epublish SO - Stem Cell Res Ther. 2020 Mar 13;11(1):114. doi: 10.1186/s13287-020-01622-w.