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Inhibiting of circ-TLK1 inhibits the progression of glioma through down-regulating PANX1 via targeting miR-17-5p

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Abstract

Glioma remains the most common malignant tumors in the central nervous system and often has poor prognosis. In recent years, it has been gradually revealed that non-coding RNA effects glioma progression. In this study, we aimed to investigate the significance of circular RNA TLK1 (Circ-TLK1) in predicting the survival of glioma patients as well as its role in glioma development via both in-vitro and in-vivo experiments. We found that Circ-TLK1 was conspicuously up-regulated in glioma tissues compared with adjacent normal tissues, and the up-regulated Circ-TLK1 was significantly correlated with glioma patients’ larger tumor volume and higher grades. Functionally, Circ-TLK1 over-expression facilitated glioma growth, migration and invasion, inhibited cell apoptosis, and accelerated PANX1/MAPK/ERK expression, while Circ-TLK1 low expression had the opposite effects. In addition, bioinformatics analysis showed that miR-17-5p was a potential target of Circ-TLK1 and targeted at PANX1. Furthermore, through dual luciferase viability assay, Circ-TLK1 acted as a competing endogenous RNA by sponging miR-17-5p, which targeted and inhibited PANX1/MAPK/ERK expression. MiR-17-5p overexpression mitigated glioma progression, which was significantly inhibited with Circ-TLK1 upregulation. In conclusion, this study confirmed a novel axis of Circ-TLK1-miR-17-5p-PANX1 in modulating glioma development, providing more references for glioma diagnosis and targeted therapy.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

BSA:

Bovine Serum Albumin

CCK8:

Cell Counting Kit-8

CircRNAs:

Circular RNAs

EC:

Endometrial Cancer

ERK:

Mitogen-Activated Protein Kinase 1

IHC:

Immunohistochemistry

LSCC:

Laryngeal Squamous Cell Carcinoma

MAPK:

Mitogen Activated Kinase-Like Protein

miRNAs:

MicroRNAs

MMP3:

Matrix Metallopeptidase 3

NTN4:

Netrin 4

PANX1:

Pannexin1

PDGF:

Platelet Derived Growth Factor

qRT-PCR:

Quantitative Reverse-Transcription Polymerase Chain Reaction

SELK:

Selenoprotein K;

VEGFA:

Vascular Endothelial Growth Factor A

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This research did not receive any specific grant from funding agencies in the public, commercial, or not- for- profit sectors.

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Contributions

WS made study concept and manuscript review; ZZW prepared and edited manuscript; ZZW, XC, QLL, YA and MW collected data; ZZW and WS analyzed the statistics; ZZW, XC and WS researched literature; ZZW, XC, QLL, YA and MW did clinical studies. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Wei Shi.

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The authors declare that they have no competing interests.

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Our study was approved by the Ethics Review Board of Second Affiliated Hospital of Xi’an Jiaotong University.

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Wang, Z., Chen, X., Liang, Q. et al. Inhibiting of circ-TLK1 inhibits the progression of glioma through down-regulating PANX1 via targeting miR-17-5p. J Mol Histol 52, 1007–1020 (2021). https://doi.org/10.1007/s10735-021-09993-x

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  • DOI: https://doi.org/10.1007/s10735-021-09993-x

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