Construction of CeRNA Regulatory Networks for Osteoporosis

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2023 Jun 16

PMID 37326104

Authors

Hongtao Chen

Hailong Wang

Xu Liu

Long Li

Yiliyaer Abudusimu

Yilihamu Tuoheti

Affiliations

Soon will be listed here.

Abstract

Osteoporosis increases the risk of fracture. Improving the diagnosis and treatment of osteoporosis has clinical applications. The differentially expressed genes (DEcircRs, DEmRs, DEmiRs) of osteoporotic patients and controls were analyzed using the GEO database, and enrichment analysis of DEmRs was performed. circRNAs and mRNAs, which were predicted to have a target relationship with DEmRs, were obtained to compare competing endogenous RNA (ceRNA) regulatory networks by comparison with differentially expressed genes. Molecular experiments were utilized to validate the expression of genes within the network. The interactions between genes within the ceRNA network were validated by luciferase reporter assays. Following overexpression of circ_0070304 in bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of the cells was assessed by Alizarin Red staining. A total of 110 intersectional DEmRs between patients with osteoporosis and controls from GSE35958 and GSE56815, which were mainly enriched in estrogen, the thyroid hormone signaling pathway, and adherens junctions were identified. A ceRNA network [circ_0070304/miR‑183‑5p/ring finger and CCCH‑type domains 2 (RC3H2)] was then constructed. Circ_0070304 acted as a sponge for miR‑183‑5p and regulated RC3H2 expression. Overexpression of circ_0070304 upregulated ROCK1 and induced osteogenic differentiation. The ceRNA regulatory network that was obtained is expected to be a new target for osteoporosis treatment and to provide new insights into the diagnosis and treatment of osteoporosis in greater depth.

References

Zhang Q, Fan L, Hou F, Dong A, Wang Y, Tong Y . New Insights into the RNA-Binding and E3 Ubiquitin Ligase Activities of Roquins. Sci Rep. 2015; 5:15660. PMC: 4614863. DOI: 10.1038/srep15660. View

Zeng Y, Zhang L, Zhu W, He H, Sheng H, Tian Q . Network based subcellular proteomics in monocyte membrane revealed novel candidate genes involved in osteoporosis. Osteoporos Int. 2017; 28(10):3033-3042. PMC: 5812280. DOI: 10.1007/s00198-017-4146-5. View

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

De Martinis M, Ginaldi L, Allegra A, Sirufo M, Pioggia G, Tonacci A . The Osteoporosis/Microbiota Linkage: The Role of miRNA. Int J Mol Sci. 2020; 21(23). PMC: 7727697. DOI: 10.3390/ijms21238887. View

Lin C, Yu S, Jin R, Xiao Y, Pan M, Pei F . Circulating miR-338 Cluster activities on osteoblast differentiation: Potential Diagnostic and Therapeutic Targets for Postmenopausal Osteoporosis. Theranostics. 2019; 9(13):3780-3797. PMC: 6587346. DOI: 10.7150/thno.34493. View

Compston J, McClung M, Leslie W . Osteoporosis. Lancet. 2019; 393(10169):364-376. DOI: 10.1016/S0140-6736(18)32112-3. View

Davis C, Dukes A, Drewry M, Helwa I, Johnson M, Isales C . MicroRNA-183-5p Increases with Age in Bone-Derived Extracellular Vesicles, Suppresses Bone Marrow Stromal (Stem) Cell Proliferation, and Induces Stem Cell Senescence. Tissue Eng Part A. 2017; 23(21-22):1231-1240. PMC: 5689127. DOI: 10.1089/ten.TEA.2016.0525. View

Gao Z, Yao K, Cai P, Long N, Cao Y, He F . Establishment of a Survival Risk Prediction Model for Adolescent and Adult Osteosarcoma Patients. Biomed Res Int. 2022; 2022:9559496. PMC: 9427311. DOI: 10.1155/2022/9559496. View

10.

Almeida M, Laurent M, Dubois V, Claessens F, OBrien C, Bouillon R . Estrogens and Androgens in Skeletal Physiology and Pathophysiology. Physiol Rev. 2016; 97(1):135-187. PMC: 5539371. DOI: 10.1152/physrev.00033.2015. View

11.

Fu M, Fang L, Xiang X, Fan X, Wu J, Wang J . Microarray analysis of circRNAs sequencing profile in exosomes derived from bone marrow mesenchymal stem cells in postmenopausal osteoporosis patients. J Clin Lab Anal. 2021; 36(1):e23916. PMC: 8761433. DOI: 10.1002/jcla.23916. View

12.

Pan X, Cen X, Zhang B, Pei F, Huang W, Huang X . Circular RNAs as potential regulators in bone remodeling: a narrative review. Ann Transl Med. 2021; 9(19):1505. PMC: 8573438. DOI: 10.21037/atm-21-2114. View

13.

De Martinis M, Sirufo M, Suppa M, Ginaldi L . IL-33/IL-31 Axis in Osteoporosis. Int J Mol Sci. 2020; 21(4). PMC: 7072890. DOI: 10.3390/ijms21041239. View

14.

Cosman F, de Beur S, LeBoff M, Lewiecki E, Tanner B, Randall S . Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014; 25(10):2359-81. PMC: 4176573. DOI: 10.1007/s00198-014-2794-2. View

15.

Maruyama T, Araki T, Kawarazaki Y, Naguro I, Heynen S, Aza-Blanc P . Roquin-2 promotes ubiquitin-mediated degradation of ASK1 to regulate stress responses. Sci Signal. 2014; 7(309):ra8. DOI: 10.1126/scisignal.2004822. View

16.

. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994; 843:1-129. View

17.

DAmelio P, Sassi F . Gut Microbiota, Immune System, and Bone. Calcif Tissue Int. 2017; 102(4):415-425. DOI: 10.1007/s00223-017-0331-y. View

18.

Liang B, Burley G, Lin S, Shi Y . Osteoporosis pathogenesis and treatment: existing and emerging avenues. Cell Mol Biol Lett. 2022; 27(1):72. PMC: 9441049. DOI: 10.1186/s11658-022-00371-3. View

19.

Benisch P, Schilling T, Klein-Hitpass L, Frey S, Seefried L, Raaijmakers N . The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors. PLoS One. 2012; 7(9):e45142. PMC: 3454401. DOI: 10.1371/journal.pone.0045142. View

20.

Williams G, Bassett J . Thyroid diseases and bone health. J Endocrinol Invest. 2017; 41(1):99-109. PMC: 5754375. DOI: 10.1007/s40618-017-0753-4. View