PMID- 34079579
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220423
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 12
DP  - 2021
TI  - Construction of a circRNA-miRNA-mRNA Regulatory Network Reveals Potential 
      Mechanism and Treatment Options for Osteosarcoma.
PG  - 632359
LID - 10.3389/fgene.2021.632359 [doi]
LID - 632359
AB  - BACKGROUND: Osteosarcoma is a common malignant primary bone tumor in adolescents 
      and children. Numerous studies have shown that circRNAs were involved in the 
      proliferation and invasion of various tumors. However, the role of circRNAs in 
      osteosarcoma remains unclear. Here, we aimed to explore the regulatory network 
      among circRNA-miRNA-mRNA in osteosarcoma. METHODS: The circRNA (GSE140256), 
      microRNA (GSE28423), and mRNA (GSE99671) expression profiles of osteosarcoma were 
      collected from the Gene Expression Omnibus (GEO) database. Differentially 
      expressed circRNAs, miRNAs and mRNAs were identified. CircRNA-miRNA interactions 
      and miRNA-mRNA interactions were determined by Circular RNA Interactome 
      (CircInteractome) database and microRNA Data Integration Portal (mirDIP) 
      database, respectively. Then, we constructed a regulatory network. Function 
      enrichment analysis of miRNA and mRNA was performed by DIANA-miRPath v3.0 and 
      Metascape database, respectively. mRNAs with significant prognostic value were 
      identified based on expression profiles from The Cancer Genome Atlas (TCGA) 
      database, and we constructed a subnetwork for them. To make the most of the 
      network, we used the CLUE database to predict potential drugs for the treatment 
      of osteosarcoma based on mRNA expression in the network. And we used the STITCH 
      database to analyze and validate the interactions among these drugs and mRNAs, 
      and to further screen for potential drugs. RESULTS: A total of 9 circRNAs, 19 
      miRNAs, 67 mRNAs, 54 pairs of circRNA-miRNA interactions and 110 pairs of 
      miRNA-mRNA interactions were identified. A circRNA-miRNA-mRNA network was 
      constructed. Function enrichment analysis indicated that these miRNAs and mRNAs 
      in the network were involved in the process of tumorigenesis and immune response. 
      Among these mRNAs, STC2 and RASGRP2 with significantly prognostic value were 
      identified, and we constructed a subnetwork for them. Based on mRNA expression in 
      the network, three potential drugs, quinacridine, thalidomide and zonisamide, 
      were screened for the treatment of osteosarcoma. Among them, quinacridine and 
      thalidomide have been proved to have anti-tumor effects in previous studies, 
      while zonisamide has not been reported. And a corresponding drug-protein 
      interaction network was constructed. CONCLUSION: Overall, we constructed a 
      circRNA-miRNA-mRNA regulatory network to investigate the possible mechanism in 
      osteosarcoma, and predicted that quinacridine, thalidomide and zonisamide could 
      be potential drugs for the treatment of osteosarcoma.
CI  - Copyright (c) 2021 He, Zhou, Wang, Xu and Cheng.
FAU - He, Yi
AU  - He Y
AD  - Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Zhou, Haiting
AU  - Zhou H
AD  - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Wang, Wei
AU  - Wang W
AD  - Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Xu, Haoran
AU  - Xu H
AD  - Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Cheng, Hao
AU  - Cheng H
AD  - Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
DEP - 20210517
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC8166411
OTO - NOTNLM
OT  - GEO
OT  - TCGA
OT  - circRNA
OT  - network
OT  - osteosarcoma
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/06/04 06:00
MHDA- 2021/06/04 06:01
PMCR- 2021/05/17
CRDT- 2021/06/03 06:40
PHST- 2020/11/23 00:00 [received]
PHST- 2021/04/20 00:00 [accepted]
PHST- 2021/06/03 06:40 [entrez]
PHST- 2021/06/04 06:00 [pubmed]
PHST- 2021/06/04 06:01 [medline]
PHST- 2021/05/17 00:00 [pmc-release]
AID - 10.3389/fgene.2021.632359 [doi]
PST - epublish
SO  - Front Genet. 2021 May 17;12:632359. doi: 10.3389/fgene.2021.632359. eCollection 
      2021.