Double-Targeted Knockdown of miR-21 and CXCR4 Inhibits Malignant Glioma Progression by Suppression of the PI3K/AKT and Raf/MEK/ERK Pathways

Liu, Feijiao; Yang, Bo

doi:10.1155/2020/7930160

Cited by 8 publications

(5 citation statements)

References 49 publications

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“…MiR-21 can also increase the expression of cyclin E1 and cyclin D1 in lung cancer cells, and increase the expression of CDK6 in laryngeal squamous cell carcinoma (Dai et al, 2019;Lyu et al, 2019). Of note, inhibition of miR-21 expression in glioma has been proved to inhibit the progression of glioma (Guan et al, 2020;Liu & Yang, 2020). Consistent with previous research, we found that FXT suppressed cell viability and promoted apoptosis in glioma by downregulating miR-21-3p.…”

Section: Discussionsupporting

confidence: 90%

Fraxetin exerts anticancer effect in glioma by suppressing MiR‐21‐3p

Yao

Pan

et al. 2021

Drug Development Research

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Fraxetin (FXT) exerts anticancer function in multiple cancers, but its function on glioma was ill‐defined. This article expounded the mechanism by which FXT exerts an anticancer effect in glioma. The effect of gradient concentration of FXT on the viability of glioma cell lines was determined by cell counting kit 8. Effects of FXT on proliferation, apoptosis, and cell cycle in glioma cell lines were determined by colony formation assay, flow cytometry, and Hoechst 33342 staining. Expressions of apoptosis‐related gene, cycle‐related gene, and glioma‐related miRNAs after FXT (25 and 50 μmol/L) treatment were determined by quantitative reverse transcription polymerase chain reaction and western blot as needed. After miR‐21‐3p overexpression, cell viability and apoptosis of glioma cell lines treated with FXT (50 μmol/L) were tested again. Although 1 μmol/L FXT had no significant effect on cell viability, 5, 10, 25, and 50 μmol/L FXT suppressed cell viability in a concentration‐dependent manner. FXT inhibited proliferation, promoted apoptosis, and induced cell cycle arrest in G0/G1 phase in glioma cell lines. These effects may be achieved by elevated expressions of Bax and cleaved caspase‐3 and diminished expressions of Bcl‐2, Bcl‐XL, cyclin E1, cyclin D1, and cyclin‐dependent kinase‐6. FXT attenuated the contents of miR‐21‐3p and miR‐455‐3p, and escalated the contents of miR‐124‐3p and miR‐7‐5p. The regulation of FXT on cell viability, proliferation and apoptosis was reversed by miR‐21‐3p overexpression. FXT suppressed the development of glioma cells by downregulating miR‐21‐3p.

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Section: Discussionsupporting

confidence: 90%

Fraxetin exerts anticancer effect in glioma by suppressing MiR‐21‐3p

Yao

Pan

et al. 2021

Drug Development Research

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“…As an extensively studied miRNA, miR-21 can mediate inflammation [ 70 ], oxidative stress [ 71 ], cell apoptosis [ 72 ], proliferation [ 73 ], and regulate multiple signal pathways, including the protein kinase B (AKT) signaling pathway [ 74 , 75 ], extracellular regulated protein kinases (ERK) signaling pathway [ 76 , 77 ], and nuclear factor kappa-B (NF- κ B) [ 78 ]. Plenty of studies have proven that miR-21 participates in the occurrence and development of tumors [ 79 , 80 ], cardiovascular [ 81 ] and lung diseases [ 82 , 83 ], glaucoma intraocular pressure [ 84 ], age-related skin wound healing [ 85 ], sepsis, and acute kidney injury [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

Liu

Yang

Mou

et al. 2022

Oxidative Medicine and Cellular Longevity

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Purpose. Our study is aimed at investigating the mechanism by which electroacupuncture (EA) promoted nerve regeneration by regulating the release of exosomes and exosome-mediated miRNA-21 (miR-21) transmission. Furthermore, the effects of Schwann cells- (SC-) derived exosomes on the overexpression of miR-21 for the treatment of PNI were investigated. Methods. A sciatic nerve injury model of rat was constructed, and the expression of miR-21 in serum exosomes and damaged local nerves was detected using RT-qPCR after EA treatment. The exosomes were identified under a transmission electron microscope and using western blotting analysis. Then, the exosome release inhibitor, GW4869, and the miR-21-5p-sponge used for the knockdown of miR-21 were used to clarify the effects of exosomal miR-21 on nerve regeneration promoted by EA. The nerve conduction velocity recovery rate, sciatic nerve function index, and wet weight ratio of gastrocnemius muscle were determined to evaluate sciatic nerve function recovery. SC proliferation and the level of neurotrophic factors were assessed using immunofluorescence staining, and the expression levels of SPRY2 and miR-21 were detected using RT-qPCR analysis. Subsequently, the transmission of exosomal miR-21 from SC to the axon was verified in vitro. Finally, the exosomes derived from the SC infected with the miR-21 overexpression lentivirus were collected and used to treat the rat SNI model to explore the therapeutic role of SC-derived exosomes overexpressing miR-21. Results. We found that EA inhibited the release of serum exosomal miR-21 in a PNI model of rats during the early stage of PNI, while it promoted its release during later stages. EA enhanced the accumulation of miR-21 in the injured nerve and effectively promoted the recovery of nerve function after PNI. The treatment effect of EA was attenuated when the release of circulating exosomes was inhibited or when miR-21 was downregulated in local injury tissue via the miR-21-5p-sponge. Normal exosomes secreted by SC exhibited the ability to promote the recovery of nerve function, while the overexpression of miR-21 enhanced the effects of the exosomes. In addition, exosomal miR-21 secreted by SC could promote neurite outgrowth in vitro. Conclusion. Our results demonstrated the mechanism of EA on PNI from the perspective of exosome-mediated miR-21 transport and provided a theoretical basis for the use of exosomal miR-21 as a novel strategy for the treatment of PNI.

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“…The relationship between the influence of different chemokines on migration and dissemination of glial tumor cells is relatively well described in the literature [29,30]. Research involving chemokine and glial tumor cells has classically attempted to limit or suppress the phenomenon of chemoattraction inducing cell migration to decrease the distant spread of tumor cells [31][32][33][34][35][36][37][38]. However, so far, this approach has not been successfully deployed in the clinic in the treatment of primary brain tumors contrary to other types of cancer [39].…”

Section: Discussionmentioning

confidence: 99%

Chemoattraction of Neoplastic Glial Cells with CXCL10, CCL2 and CCL11 as a Paradigm for a Promising Therapeutic Approach for Primary Brain Tumors

Déry

Charest

Guérin

et al. 2021

IJMS

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Chemoattraction is a normal and essential process, but it can also be involved in tumorigenesis. This phenomenon plays a key role in glioblastoma (GBM). The GBM tumor cells are extremely difficult to eradicate, due to their strong capacity to migrate into the brain parenchyma. Consequently, a complete resection of the tumor is rarely a possibility, and recurrence is inevitable. To overcome this problem, we proposed to exploit this behavior by using three chemoattractants: CXCL10, CCL2 and CCL11, released by a biodegradable hydrogel (GlioGel) to produce a migration of tumor cells toward a therapeutic trap. To investigate this hypothesis, the agarose drop assay was used to test the chemoattraction capacity of these three chemokines on murine F98 and human U87MG cell lines. We then studied the potency of this approach in vivo in the well-established syngeneic F98-Fischer glioma-bearing rat model using GlioGel containing different mixtures of the chemoattractants. In vitro assays resulted in an invasive cell rate 2-fold higher when chemokines were present in the environment. In vivo experiments demonstrated the capacity of these specific chemoattractants to strongly attract neoplastic glioblastoma cells. The use of this strong locomotion ability to our end is a promising avenue in the establishment of a new therapeutic approach in the treatment of primary brain tumors.

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Double-Targeted Knockdown of miR-21 and CXCR4 Inhibits Malignant Glioma Progression by Suppression of the PI3K/AKT and Raf/MEK/ERK Pathways

Cited by 8 publications

References 49 publications

Fraxetin exerts anticancer effect in glioma by suppressing MiR‐21‐3p

Fraxetin exerts anticancer effect in glioma by suppressing MiR‐21‐3p

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

Chemoattraction of Neoplastic Glial Cells with CXCL10, CCL2 and CCL11 as a Paradigm for a Promising Therapeutic Approach for Primary Brain Tumors

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