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CircRNA BIRC6 promotes non-small cell lung cancer cell progression by sponging microRNA-145

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Abstract

Purpose

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality world-wide. Recently, a number of circular RNAs (circRNAs) has been found to be differentially expressed in human NSCLCs, correlating with clinico-pathological features. As yet, the expression and potential role of circRNA BIRC6 (circBIRC6) in NSCLC have not been studied.

Methods

Expression of circBIRC6 and its target microRNA-145 (miR-145) in human NSCLC cells and tissues was assessed using qRT-PCR. In vitro genetic strategies were used to exogenously alter circBIRC6 and miR-145 expression. Their impact on in vitro and in vivo NSCLC cell behavior was studied.

Results

We found that circBIRC6 was upregulated in primary human NSCLC tissues and NSCLC cells, whereas its potential target, miR-145, was downregulated. In A549 NSCLC cells and primary human NSCLC cells, shRNA-induced silencing of circBIRC6 potently inhibited their growth, proliferation, migration and invasion. Conversely, we found that exogenous overexpression of circBIRC6 promoted these characteristics. Using RNA immunoprecipitation (RIP) in A549 cells, we found that Argonaute 2 (Ago2) immunoprecipitated together with both circBIRC6 and miR-145. Additional studies revealed that the miR-145 level increased after circBIRC6 silencing in A549 cells, but decreased after circBIRC6 overexpression. Of note, we found that the circBIRC6 silencing-induced anti-A549 activity could be attenuated by a miR-145 inhibitor. Lastly, we found that circBIRC6 silencing inhibited the growth of NSCLC xenografts in severe combined immunodeficient mice.

Conclusions

From our data we conclude that circBIRC6 overexpression promotes NSCLC cell progression, possibly by sponging miR-145.

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Availability of supporting data

All data generated during this study are included in this article.

Abbreviations

Ago2:

Argonaute 2

circRNA:

circular RNA

circBIRC6:

circRNA BIRC6

ECL:

enhanced chemiluminescence

EMT:

epithelial-mesenchymal transition

FSCN1:

fascin1

FBS:

fetal bovine serum

mTOR:

mammalian target of rapamycin

miR-145:

microRNA-145

ncRNA:

non-coding RNA

NSCLC:

non-small cell lung cancer

PI:

propidium iodide

RIP:

RNA immunoprecipitation

SCID:

severe combined immunodeficient

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Acknowledgements

We thank Dr. Jiang from Nanjing Medical University for manuscript editing and study design.

Authors’ information

Not applicable.

Funding

This project was supported by a Medicine and Health Grant from Wenzhou Municipal Science and Technology Bureau (Y20180213). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. Han Yang and Mengjing Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Han Yang, Lihao Zhao & Gang Li

  2. Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, South Bai-xiang street, Ouhai District, Wenzhou, 325000, Zhejiang, China

    Mengjing Zhao & Yuxia Duan

  3. Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China

    Ping Li

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  1. Han Yang
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All listed authors participated in designing the study, performing the experiments and the statistical analyses, and writing the manuscript. All authors have read and approved the final version.

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Correspondence to Ping Li, Yuxia Duan or Gang Li.

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This study was approved by the Ethics Committee of Wenzhou Medical University.

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Yang, H., Zhao, M., Zhao, L. et al. CircRNA BIRC6 promotes non-small cell lung cancer cell progression by sponging microRNA-145. Cell Oncol. 43, 477–488 (2020). https://doi.org/10.1007/s13402-020-00503-x

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