Circ_0000020 elevates the expression of PIK3CA and facilitates the malignant phenotypes of glioma cells via targeting miR-142-5p

Wang, Xu; Zhu, Ye

doi:10.1186/s12935-021-01767-5

Cited by 8 publications

(3 citation statements)

References 46 publications

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“…MORC2 is highly expressed in human glioma cells compared with normal glial cells. Human glioma cell lines have been used widely in studies of glioma pathogenesis (14)(15)(16). First of all, the expression of MORc2 in several human glioma cell lines (U251, SHG44, LN229 and T98G) was determined using RT-qPCR.…”

Section: Resultsmentioning

confidence: 99%

Microrchidia family CW‑type zinc finger 2 promotes the proliferation, invasion, migration and epithelial‑mesenchymal transition of glioma by regulating PTEN/PI3K/AKT signaling via binding to N‑myc downstream regulated gene 1 promoter

et al. 2021

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Glioma is a common malignant tumor of the central nervous system with high incidence and mortality. The present study aimed to investigate the role of Microrchidia family CW-type zinc finger 2 (MORC2) in the development of glioma. Firstly, MORc2 expression was detected in several glioma cell lines (U251, SHG44, LN229 and T98G). Following MORC2 silencing, cell proliferation was evaluated using the cell Counting Kit-8 assay and the expression of proliferation-related proteins was assessed via immunofluorescence staining or western blotting. cell invasion and migration were assessed using transwell and wound healing assays, respectively. Western blotting and immunofluorescence staining were employed to determine the expression of epithelial-mesenchymal transition (EMT)-associated proteins. The protein expression of N-myc downstream regulated gene 1 (NDRG1) and PTEN/PI3K/AKT signaling was determined with western blot analysis. Then, the luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to evaluate the binding between MORC2 and NDRG1 promoter. Subsequently, cellular functional experiments were performed to assess the effects of NdRG1 on the progression of glioma after NdRG1 and MORc2 overexpression. In addition, tumor-bearing experiments were conducted using a U251 tumor-bearing nude mice model to detect tumor growth. The expression of proliferation (proliferating cell nuclear antigen, cyclin-dependent kinase 2 and cyclin E1), migration [matrix metalloproteinase (MMP)2 and MMP9], EMT (E-cadherin, N-cadherin and Vimentin) and PTEN/PI3K/AKT signaling proteins in tumor tissues was examined with immunohistochemistry assay or western blotting. Results revealed that MORc2 was notably unregulated in glioma cells compared with the normal human astrocyte. Loss-function of MORc2 inhibited the proliferation, invasion, migration and EMT of glioma cells. Importantly, MORc2 silencing upregulated NdRG1 expression and inactivated PTEN/PI3K/AKT signaling. Additionally, the luciferase reporter-and ChIP assays confirmed that MORC2 could bind to the NdRG1 promoter. NdRG1 upregulation suppressed the progression of glioma and these effects were partially reversed by MORc2 overexpression. Results of tumor-bearing experiments suggested that gain-function of NdRG1 inhibited tumor growth and downregulated the expression of proliferation, migration and EMT-related proteins in tumorous tissue in U251 tumor-bearing mice, which was partially counteracted after MORc2 overexpression. In addition, MORc2 overexpression abrogated the inhibitory effect of NdRG1 on PTEN/PI3K/AKT signaling. In summary, MORC2 promoted the progression of glioma by inactivation of PTEN/PI3K/AKT signaling via binding to NdRG1 promoter, providing a novel and potent target for the treatment of glioma.

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Section: Resultsmentioning

confidence: 99%

Microrchidia family CW‑type zinc finger 2 promotes the proliferation, invasion, migration and epithelial‑mesenchymal transition of glioma by regulating PTEN/PI3K/AKT signaling via binding to N‑myc downstream regulated gene 1 promoter

et al. 2021

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“…It is widely accepted that CircRNA-miRNA network has a close relationship with osteogenic differentiation [ 18 ]. In a recent study, it was reported that Circ_0000020 promotes glioma cell growth, and links with poor prognosis [ 19 ]. However, the role of Circ_0000020 in regulating osteogenic differentiation is not studied well.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circ_0000020 promotes osteogenic differentiation to reduce osteoporosis via sponging microRNA miR-142-5p to up-regulate Bone Morphogenetic Protein BMP2

Zhou

Miao

et al. 2021

Bioengineered

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This study was designed to study functions of Circ_0000020 during osteogenic differentiation. First, we used RT-qPCR to detect the expression of Circ_0000020, miR-142-5p and osteogenesisrelated genes, whereas western blot analysis detected the expression of osteogenesis markers after the osteogenic differentiation of primary BMSCs isolated from rats. Alkaline phosphatase (ALP) activity and alizarin red Sstaining validated osteoblast phenotypes. Flow cytometry was used to detect cell apoptosis. Sh-Circ_0000020 was used to study the function of Circ_0000020 in osteogenic differentiation of BMSCs. Luciferase assay and RNA immunoprecipitation were used to validate the interaction between Circ_0000020 and miR-142-5p, and BMP2 and miR-142-5p. Cotransfection of miR-142-5p and sh-Circ_0000020 was used to verify the downstream signaling pathway. Circ_0000020 expression was up-regulated during osteogenic differentiation, whereas miR-142-5p expression was significantly decreased. Silencing Circ_0000020 inhibited osteogenic differentiation and promoted apoptosis, and inhibited ALP activity and mineralization ability. Moreover, Circ_0000020 interacts directly with miR-142-5p which binds to the BMP2 3 UTR and inhibits its expression. Additionally, co-transfection of miR-142-5p inhibitors and sh-Circ_0000020 rescued down-regulated BMP2, increased the expression osteogenesis-related gene expressions, and thereby rescued the inhibition of osteogenic differentiation induced by Circ_0000020 silencing. Furthermore, co-transfection of miR-142-5p inhibitors and sh-Circ_0000020 reversed Circ_0000020 silencing-induced downregulation of p-Smad1/5/8, Runx2, and Osterix protein levels. Circ_0000020 regulates BMP2 expression through sponging miR-142-5p as ceRNA, thereby positively regulating BMSCs osteogenic differentiation through Circ_0000020/miR-142-5p/BMP2/ SMAD-dependent signaling pathway.

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“…Studies have shown that circRNA_104348 can promote hepatocellular carcinoma progression by modulating the miR-187-3p/RTKN2 (Rhotekin 2) axis 12 . Circ_0000020 can elevate the expression of PIK3CA (phosphatidylinositol 3-kinase C) and facilitate the malignant phenotypes of glioma cells by targeting miR-142-5p 13 . An increasing number of circRNAs have been found to be unbalanced in LUAC and can be used as therapeutic targets in the future.…”

Section: Introductionmentioning

confidence: 99%

hsa_circ_0008234 inhibits the progression of lung adenocarcinoma by sponging miR-574-5p

Jiang

et al. 2021

Cell Death Discov.

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AbstractcircRNAs are a novel type of noncoding RNA (ncRNA) that have been identified as an important regulator of gene expression and play a part in the progression of various diseases. However, the function of circ_0008234 in lung adenocarcinoma (LUAC) remains unknown. Through the GEO (Gene Expression Omnibus) database, circ_0008234 was first found to be downregulated in LUAC tissues. It could inhibit cell growth and accelerate apoptosis in vitro and in vivo. In terms of its possible mechanism, circ_0008234 mainly was present in the cytoplasm and competed with miR-574-5p to regulate RND3 (Rho family GTPase 3). Our results revealed that circ_0008234 inhibited the progression of LUAC through a competing endogenous RNA (ceRNA)-based mechanism and provided potential biomarkers and therapeutic targets for LUAC treatment.

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Circ_0000020 elevates the expression of PIK3CA and facilitates the malignant phenotypes of glioma cells via targeting miR-142-5p

Cited by 8 publications

References 46 publications

Microrchidia family CW‑type zinc finger 2 promotes the proliferation, invasion, migration and epithelial‑mesenchymal transition of glioma by regulating PTEN/PI3K/AKT signaling via binding to N‑myc downstream regulated gene 1 promoter

Microrchidia family CW‑type zinc finger 2 promotes the proliferation, invasion, migration and epithelial‑mesenchymal transition of glioma by regulating PTEN/PI3K/AKT signaling via binding to N‑myc downstream regulated gene 1 promoter

Circular RNA circ_0000020 promotes osteogenic differentiation to reduce osteoporosis via sponging microRNA miR-142-5p to up-regulate Bone Morphogenetic Protein BMP2

hsa_circ_0008234 inhibits the progression of lung adenocarcinoma by sponging miR-574-5p

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