Circular RNAs as potential regulators in bone remodeling: a narrative review

Pan, Xuefeng; Cen, Xiao; Zhang, Bo; Pei, Fang; Huang, Wei; Huang, Xinqi

doi:10.21037/atm-21-2114

Cited by 16 publications

(13 citation statements)

References 113 publications

(138 reference statements)

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“…By modulating cell metabolism ( 15 ), cell proliferation ( 16 ), cell apoptosis ( 17 ), and other functions ( 18 ), circRNAs are involved in the incidence and development of some diseases, such as cancers ( 19 ), neurological diseases ( 20 ), heart diseases ( 21 ), and endocrine diseases ( 22 ), and circRNAs can function as therapeutic targets and biomarkers. Meanwhile, emerging researches indicated that circRNAs are also potential regulators of osteoporosis ( 23 ). For example, some studies revealed that hsa_Circ_0001275, hsa_circ_0002060, and hsa_circ_0006859 are recognized as potential novel diagnostic biomarkers of osteoporosis ( 2 , 24 , 25 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of Serum Exosome-Derived circRNA-miRNA-TF-mRNA Regulatory Network in Postmenopausal Osteoporosis Using Bioinformatics Analysis and Validation in Peripheral Blood-Derived Mononuclear Cells

2022

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BackgroundOsteoporosis is one of the most common systemic metabolic bone diseases, especially in postmenopausal women. Circular RNA (circRNA) has been implicated in various human diseases. However, the potential role of circRNAs in postmenopausal osteoporosis (PMOP) remains largely unknown. The study aims to identify potential biomarkers and further understand the mechanism of PMOP by constructing a circRNA-associated ceRNA network.MethodsThe PMOP-related datasets GSE161361, GSE64433, and GSE56116 were downloaded from the Gene Expression Omnibus (GEO) database and were used to obtain differentially expressed genes (DEGs). Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to determine possible relevant functions of differentially expressed messenger RNAs (mRNAs). The TRRUST database was used to predict differential transcription factor (TF)-mRNA regulatory pairs. Afterwards, combined CircBank and miRTarBase, circRNA-miRNA as well as miRNA-TF pairs were constructed. Then, a circRNA-miRNA-TF-mRNA network was established. Next, the correlation of mRNAs, TFs, and PMOP was verified by the Comparative Toxicogenomics Database. And expression levels of key genes, including circRNAs, miRNAs, TFs, and mRNAs in the ceRNA network were further validated by quantitative real-time PCR (qRT-PCR). Furthermore, to screen out signaling pathways related to key mRNAs of the ceRNA network, Gene Set Enrichment Analysis (GSEA) was performed.ResultsA total of 1201 DE mRNAs, 44 DE miRNAs, and 1613 DE circRNAs associated with PMOP were obtained. GO function annotation showed DE mRNAs were mainly related to inflammatory responses. KEGG analysis revealed DE mRNAs were mainly enriched in osteoclast differentiation, rheumatoid arthritis, hematopoietic cell lineage, and cytokine-cytokine receptor interaction pathways. We first identified 26 TFs and their target mRNAs. Combining DE miRNAs, miRNA-TF/mRNA pairs were obtained. Combining DE circRNAs, we constructed the ceRNA network contained 6 circRNAs, 4 miRNAs, 4 TFs, and 12 mRNAs. The expression levels of most genes detected by qRT-PCR were generally consistent with the microarray results. Combined with the qRT-PCR validation results, we eventually identified the ceRNA network that contained 4 circRNAs, 3 miRNAs, 3 TFs, and 9 mRNAs. The GSEA revealed that 9 mRNAs participate in many important signaling pathways, such as “olfactory transduction”, “T cell receptor signaling pathway”, and “neuroactive ligand-receptor interaction”. These pathways have been reported to the occurrence and development of PMOP. To sum up, key mRNAs in the ceRNA network may participate in the development of osteoporosis by regulating related signal pathways.ConclusionsA circRNA-associated ceRNA network containing TFs was established for PMOP. The study may help further explore the molecular mechanisms and may serve as potential biomarkers or therapeutic targets for PMOP.

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Section: Introductionmentioning

confidence: 99%

Identification of Serum Exosome-Derived circRNA-miRNA-TF-mRNA Regulatory Network in Postmenopausal Osteoporosis Using Bioinformatics Analysis and Validation in Peripheral Blood-Derived Mononuclear Cells

2022

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“…Circular RNAs (circRNAs) are a class of covalently closed RNAs widely expressed in eukaryotic cells 12–14 . They are usually derived from reverse splicing of transcripts by a non‐classical splicing mechanism 15–17 .…”

Section: Introductionmentioning

confidence: 99%

“…Circular RNAs (circRNAs) are a class of covalently closed RNAs widely expressed in eukaryotic cells. 12 , 13 , 14 They are usually derived from reverse splicing of transcripts by a non‐classical splicing mechanism. 15 , 16 , 17 Although the majority of circRNAs do not code for proteins, some circRNAs were reported to be translated into protein products in cancer cells with unclear functions.…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10][11] Underatdinsing the molecular mechanisms of cancer progression could provide novel insights into targeted therapies for cancers with high level of maligancny.Circular RNAs (circRNAs) are a class of covalently closed RNAs widely expressed in eukaryotic cells. [12][13][14] They are usually derived from reverse splicing of transcripts by a non-classical splicing…”

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confidence: 99%

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Hsa_hsa_circ_0081069 promotes the progression of colorectal cancer through sponging miR‐665 and regulating E2F3 expression

Xie

Jin

et al. 2022

Clinical Laboratory Analysis

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Background Circular RNAs (circRNAs) have been implicated in the initiation and development of various cancers. This study explored the potential contribution of hsa_hsa_circ_0081069 in the progression of colorectal cancer (CRC). Methods The gene expression was analyzed by qRT‐PCR. Functional roles of hsa_circ_0081069 were examined by shRNA‐mediated silencing using CCK‐8 proliferation assay, Transwell migration and invasion assay, tube formation assay. The tumorigenesis and metastasis of CRC cells were assess in a xenograft mouse model. Results Hsa_circ_0081069 was significantly upregulated in CRC tissues and cells. Hsa_circ_0081069 knockdown suppressed the proliferation, migration and invasion in CRC cells, as well as the angiogenesis. Silencing hsa_circ_0081069 also impaired the tumorigenesis of CRC cells in a xenograft mouse model. Furthermore, miR‐665 was identified as an interacting partner of hsa_circ_0081069, which was negatively regulated by hsa_circ_0081069. miR‐665 targeted the mRNA of E2F3 to suppress its expression. We further demonsatred that miR‐665/E2F3 axis mediated the functional role of hsa_circ_0081069 in regulating the malignant phenotype of CRC cells. Conclusions Collectively, our study suggests that hsa_circ_0081069 could serve as a prognostic marker in progression of CRC. Targeting hsa_circ_0081069 and miR‐665/E2F3 axis could serve as potential therapeutic strategies for CRC treatment.

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“…circRNA can lift the repressive effect of miR-NAs on their target genes through miRNA sponge action [7,8]. circRNAs are irregularly expressed in countless tumors and are involved in regulating NF-κB, PI3K/AKT, TGF-β, and JAK-STAT signaling pathways [9][10][11][12], thereby affecting tumor development. It was shown that circVANGL1 in NSCLC inhibits miR-195 by adsorbing miR-195 and thus negatively regulates downstream genes [13].…”

Section: Introductionmentioning

confidence: 99%

hsa_circ_0000518 Facilitates Non-Small-Cell Lung Cancer Progression via Moderating miR-330-3p and Positively Regulating SLC1A5

Shi

Sui

et al. 2022

Journal of Immunology Research

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Background/Aim. Non-small-cell lung cancer (NSCLC) is the principal agent of cancer deaths globally. The goal of this study was to determine how circular RNA_0000518 (circ_0000518) regulates tumor progression. Materials/Methods. circ_0000518 was selected as a study target involved in NSCLC from GEO (Gene Expression Omnibus) database. circ_0000518 level was gauged by qRT-PCR. It was confirmed as circRNA by actinomycin D inhibition and RNase R assay. Subcellular localization of circ_0000518 was identified by FISH. Cell function was determined by CCK-8, Transwell, and western blot. Glutamine metabolic factors were detected by ELISA. The target regulation relationship between genes was clarified by dual-luciferase reporter assay. In vivo models were established to evaluate the impact of circ_0000518 on tumor growth. Immunohistochemical staining for Ki67, vimentin, and E-cadherin was used to detect cell proliferation and metastasis, respectively. Results. circ_0000518 expression was enhanced in NSCLC. si-circ_0000518 inhibited cell proliferation, invasion, and glutamine metabolism. circ_0000518 functioned as a molecular sponge for miR-330-3p, and inhibition of miR-330-3p in cells markedly reversed circ_0000518 interference-mediated antitumor effects. miR-330-3p interacted with 3 ′ -UTR of SLC1A5. miR-330-3p inhibitor-mediated protumor effect was remarkably reversed in cells after the knockdown of SLC1A5. circ_0000518 knockdown reduced glutamine, glutamate, and α-KG by targeting miR-330-3p. Intertumoral injection of circ_0000518 shRNA adeno-associated virus effectively halted xenograft tumor growth. Conclusion. The current study revealed that circ_0000518 may have a prooncogenic function in the formation and progression of NSCLC, which might be achieved through moderating the miR-330-3p/SLC1A5 axis.

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Circular RNAs as potential regulators in bone remodeling: a narrative review

Cited by 16 publications

References 113 publications

Identification of Serum Exosome-Derived circRNA-miRNA-TF-mRNA Regulatory Network in Postmenopausal Osteoporosis Using Bioinformatics Analysis and Validation in Peripheral Blood-Derived Mononuclear Cells

Identification of Serum Exosome-Derived circRNA-miRNA-TF-mRNA Regulatory Network in Postmenopausal Osteoporosis Using Bioinformatics Analysis and Validation in Peripheral Blood-Derived Mononuclear Cells

Hsa_hsa_circ_0081069 promotes the progression of colorectal cancer through sponging miR‐665 and regulating E2F3 expression

hsa_circ_0000518 Facilitates Non-Small-Cell Lung Cancer Progression via Moderating miR-330-3p and Positively Regulating SLC1A5

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