PMID- 35993048 OWN - NLM STAT- MEDLINE DCOM- 20220823 LR - 20220912 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2022 DP - 2022 TI - Integrated Analysis of Crucial Genes and miRNAs Associated with Osteoporotic Fracture of Type 2 Diabetes. PG - 3921570 LID - 10.1155/2022/3921570 [doi] LID - 3921570 AB - PURPOSE: The aim of this study is to explore pathological mechanisms of bone fragility in type 2 diabetes mellitus (T2DM) patients. METHODS: Identifying common genes for T2DM and osteoporosis by taking the intersection is shared by the Comparative Toxicogenomics Database (CTD), DISEASES, and GeneCards databases. The differentially expressed genes (DEGs) and the differentially expressed miRNAs (DEMs) were identified by analyzing the Gene Expression Omnibus (GEO) datasets (GSE35958, GSE43950, and GSE70318). FunRich and miRNet were applied to predict potential upstream transcription factors and downstream target genes of candidate DEMs, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore potential mechanisms using Metascape. Eventually, a miRNA-gene network was constructed by Cytoscape software. RESULTS: 271 common targets and 35 common DEGs between T2DM and osteoporosis were screened out in the above databases, and a total of ten DEMs were obtained in the GSE70318. SP1 was predicted to potentially regulate most of the DEMs. Enrichment analysis showed the PI3K-Akt signaling pathway and AGE-RAGE signaling pathway in diabetic complications may play an important role in diabetic skeletal fragility. Two genes (NAMPT and IGFBP5) were considered as key genes involving in the development of diabetic osteoporosis. Through the construction of the miRNA-gene network, most of the hub genes were found to be potentially modulated by miR-96-5p and miR-7-5p. CONCLUSION: The study uncovered several important genes, miRNAs, and pathological mechanisms involved in diabetic skeletal fragility, among which the PI3K-Akt signaling pathway and AGE-RAGE signaling pathway in diabetic complications may play important roles. CI - Copyright (c) 2022 Liang Mo et al. FAU - Mo, Liang AU - Mo L AUID- ORCID: 0000-0002-5554-6196 AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405 Guangdong Province, China. FAU - Wang, Zhangzheng AU - Wang Z AUID- ORCID: 0000-0003-3871-5143 AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405 Guangdong Province, China. FAU - Huang, Haoran AU - Huang H AUID- ORCID: 0000-0002-6450-2486 AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405 Guangdong Province, China. FAU - Li, Jianxiong AU - Li J AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405 Guangdong Province, China. FAU - Ma, Chao AU - Ma C AD - Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, 51000 Guangdong Province, China. FAU - Zhang, Jiahao AU - Zhang J AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405 Guangdong Province, China. FAU - Huang, Fayi AU - Huang F AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405 Guangdong Province, China. FAU - He, Wei AU - He W AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405 Guangdong Province, China. FAU - Liu, Yuhao AU - Liu Y AUID- ORCID: 0000-0002-0447-6677 AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405 Guangdong Province, China. FAU - Zhou, Chi AU - Zhou C AUID- ORCID: 0000-0003-1905-9494 AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405 Guangdong Province, China. LA - eng PT - Journal Article DEP - 20220810 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (Glycation End Products, Advanced) RN - 0 (MIRN7 microRNA, human) RN - 0 (MIRN96 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Receptor for Advanced Glycation End Products) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Computational Biology MH - *Diabetes Mellitus, Type 2/complications/genetics/metabolism MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic MH - Glycation End Products, Advanced/genetics/metabolism MH - Humans MH - *MicroRNAs/genetics/metabolism MH - *Osteoporosis/etiology/genetics/metabolism MH - *Osteoporotic Fractures/etiology/genetics/metabolism MH - Phosphatidylinositol 3-Kinases/genetics MH - Proto-Oncogene Proteins c-akt/genetics MH - Receptor for Advanced Glycation End Products/genetics/metabolism PMC - PMC9385370 COIS- The authors declare that they have no conflicts of interest. EDAT- 2022/08/23 06:00 MHDA- 2022/08/24 06:00 PMCR- 2022/08/10 CRDT- 2022/08/22 04:37 PHST- 2022/01/05 00:00 [received] PHST- 2022/07/17 00:00 [accepted] PHST- 2022/08/22 04:37 [entrez] PHST- 2022/08/23 06:00 [pubmed] PHST- 2022/08/24 06:00 [medline] PHST- 2022/08/10 00:00 [pmc-release] AID - 10.1155/2022/3921570 [doi] PST - epublish SO - Biomed Res Int. 2022 Aug 10;2022:3921570. doi: 10.1155/2022/3921570. eCollection 2022.