Circular RNA Circ_0006282 Promotes Cell Proliferation and Metastasis in Gastric Cancer by Regulating MicroRNA-144-5p/Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein β Axis

Ye, Hua; Wang, Hailong; Wang, Haizhen; Wu, Xiangming; Yang, Li; Wang, Chenlin; Li, Xi; Li, Min; Wang, Lina; Dong, Changcheng; Yin, Fei

doi:10.2147/cmar.s283952

Cited by 12 publications

(7 citation statements)

References 37 publications

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“…Other evidence has shown that miR-let-7c-5p inhibits the proliferation and migration of cervical carcinoma cells [ 26 ] and negatively regulates NLRC5 protein expression in ethanol-induced hepatic injury [ 27 ]. Interestingly, miR-149-5p is capable of inhibiting the growth of gastric cancer, cholangiocarcinoma and glioblastoma [ 28 – 30 ]. MiR-149-5p can also inhibit M1 macrophage-associated inflammation in experimental abdominal aortic aneurysm formation [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

miR-let-7c-5p and miR-149-5p inhibit proinflammatory cytokine production in osteoarthritis and rheumatoid arthritis synovial fibroblasts

Law

Lee

Lin

et al. 2021

Aging

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Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common types of arthritis. Both are characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. miRNAs play critical roles in the disease processes of arthritic disorders. However, little is known about the effects of miRNAs on critical inflammatory cytokine production with OA and RA progression. Here, we found higher levels of proinflammatory cytokines including interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in human OA and RA synovial fibroblasts (SFs) compared with normal SFs. Searches of open-source microRNA (miRNA) software determined that miR-let-7c-5p and miR-149-5p interfere with IL-1β, IL-6 and TNF-α transcription; levels of all three proinflammatory cytokines were lower in human OA and RA patients compared with normal controls. Anti-inflammatory agents dexamethasone, celecoxib and indomethacin reduced proinflammatory cytokine production by promoting the expression of miR-let-7c-5p and miR-149-5p. Similarly, ibuprofen and methotrexate also enhanced miR-let-7c-5p and miR-149-5p expression in human SFs. The evidence suggests that increasing miR-let-7c-5p and miR-149-5p expression is a novel strategy for OA and RA.

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Section: Discussionmentioning

confidence: 99%

miR-let-7c-5p and miR-149-5p inhibit proinflammatory cytokine production in osteoarthritis and rheumatoid arthritis synovial fibroblasts

Law

Lee

Lin

et al. 2021

Aging

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“…The myoblast proliferation was promoted after miR-144-5p treatment, which was the opposite of what was found in gastric cancer cells, that miR-144-5p could inhibit the cell proliferation [ 24 ]; therefore, we believed that miR-144-5p promoted growth and displayed anti-cancer activities. As a member of the dipeptidyl peptidase 4 protein family, FAP has both dipeptidyl peptidase and endopeptidase activities, could modulate fibrinolysis, seems to mostly appear in many kinds of fibroblasts, and is essential for cell survival [ 26 ].…”

Section: Discussionmentioning

confidence: 77%

“…It has been reported that some miRNA families like miR-1 and miR-133 family were myogenic specific and could regulate myogenesis [ 21 , 22 ]. miR-144-5p as a member of miR-144, could target RANKL and suppress cytokines expression [ 23 ] and involve in circ_0006282/miR-144-5p/YWHAB axis [ 24 ], but no research has reported its role on myogenesis.…”

Section: Introductionmentioning

confidence: 99%

CircMGA Depresses Myoblast Proliferation and Promotes Myotube Formation through miR-144-5p/FAP Signal

Wang

Zhang

et al. 2022

Animals

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Circular RNAs are endogenous and abundant in skeletal muscle, and may not only be involved in regulating gene expression in a variety of ways, but also function as important regulators in poultry muscle development. Our previous research found that circMGA was differentially expressed during chicken muscle embryo development; however, as a novel circular RNA, the regulating mechanism of circMGA in myogenesis has never been studied before. In this study, we aimed to investigate the functional roles and related molecular mechanisms of circMGA in chicken primary myoblast cells. CircMGA originated from the exon 13–14 of MGA gene, was differentially expressed during embryo development and myogenesis differentiation, and could inhibit myoblast cell proliferation by repressing cell cycle related genes and promote myotube formation through MyoD and MyHC. Biotin-labeled miRNA pulldown assay and luciferase reporter assay result showed that miR-144-5p could directly target circMGA and FAP, indicating that there could be a competing endogenous RNA mechanism between circMGA and FAP. In function, miR-144-5p showed opposite regulation in myoblast cell with circMGA and FAP, just as expected. circMGA co-transfected with miR-144-5p or si-FAP could effectively eliminate the inhibition of miR-144-5p on myoblast proliferation and differentiation. In conclusion, we found a novel circRNA, named circMGA, which generated from the 13–14 exon of the MGA gene, and could inhibit myoblast proliferation and promote myotube formation by acting as the sponge of miR-144-5p and through miR-144-5p/FAP signal. Moreover, circMGA could effectively eliminate the inhibition of miR-144-5p on myoblast differentiation, thus releasing FAP and promoting myotube formation.

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“…In another study investigating the effects of circ_0006282 and miR-144-5p in gastric cancer, a regulatory network with YWHAB was observed. Notably, YWHAB was positively modulated by miR-144-5p expression (21). miR-542-5p, a predictive breast cancer biomarker, is correlated with poor patient survival when overexpressed in tamoxifen-treated ER + ve breast cancer and YWHAB is a downstream target of miR-542-5p (22).…”

Section: Introductionmentioning

confidence: 94%

Investigating the Roles of YWHAB in Breast Cancer

Winstone,

Gatien,

GOPAUL

et al. 2024

Preprint

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Background: miR-526b and miR-655 have been shown to promote aggressive breast cancer phenotypes. Analysis of cell-free secretions of MCF7-miRNA-high cells identified eight differentially secreted proteins, including 14-3-3 Beta (YWHAB). Here, we investigated the roles of YWHAB in breast cancer and tested its potential as a biomarker. Methods: Breast tumor cell lines MCF7, SKBR3, Hs578T, MCF7-COX2 and stable miRNA-overexpressing MCF7-miR526b, MCF7-miR655, SKBR3-526b cells were used in vitro assays including mRNA, protein expression, and functional assays. In silico data was used to support our findings by identifying potential links between miRNAs and YWHAB and to test diagnostic and prognostic biomarker potential. Biomarker potential was validated using breast tumor biopsy tissue and plasma samples. Results: YWHAB expression is significantly upregulated in miRNA-overexpressing cell lines both at total RNA and secretory RNA levels. These miRNAs have previously been shown to increase cell migration. Following YWHAB-KD cell migration and proliferation decreased, E-Cad expression increased, and Vimentin decreased, evidently showing YWHAB involved in EMT. In silico data showed increased expression of YWHAB mRNA in breast cancer biopsy tissue and blood plasma and increased YWHAB protein in breast tumors. High expression of YWHAB is associated with poor breast cancer patient survival. YWHAB expression was measured in breast tissues and blood plasma and found to be significantly high in all advanced stages and hormonal subtypes of tumors, compared to control tissue. YWHABshowed high sensitivity as a tumour biomarker (AUC of 0.7340, p = 0.0012) and in combination with pri-miR526b showed strong potential as a blood biomarker (AUC of 0.711, p = 0.032). Conclusion: High expression of YWHAB is associated with poor survival. It can be used as a prognostic marker, and therapeutic target in aggressive cancers to mitigate cell migration. In combination with pri-miR526b, YWHAB is a promising blood biomarker for breast cancer detection.

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Circular RNA Circ_0006282 Promotes Cell Proliferation and Metastasis in Gastric Cancer by Regulating MicroRNA-144-5p/Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein β Axis

Cited by 12 publications

References 37 publications

miR-let-7c-5p and miR-149-5p inhibit proinflammatory cytokine production in osteoarthritis and rheumatoid arthritis synovial fibroblasts

miR-let-7c-5p and miR-149-5p inhibit proinflammatory cytokine production in osteoarthritis and rheumatoid arthritis synovial fibroblasts

CircMGA Depresses Myoblast Proliferation and Promotes Myotube Formation through miR-144-5p/FAP Signal

Investigating the Roles of YWHAB in Breast Cancer

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