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RETRACTED ARTICLE: circ_001504 promotes the development of renal cell carcinoma by sponging microRNA-149 to increase NUCB2

Cancer Gene Therapy volume 28, pages 667–678 (2021)Cite this article

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This article was retracted on 29 May 2023

A Correction to this article was published on 30 December 2021

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Abstract

Renal cell carcinoma (RCC) accounts for over 90% of primary renal tumors in adults. Although treatment approaches have steadily improved over the years, the prognosis outcome remains poor. With the aim of developing novel targets for RCC treatment, we explored the role of the circular RNA (circRNA) circ_001504 in the progression of RCC. We initially detected the expression of circ_001504 and microRNA (miRNA)-149 in RCC tissues and cells. RT-qPCR results showed that circ_001504 was highly expressed in RCC tissues, whereas miR-149 was poorly expressed. Interestingly, downregulation of circ_001504 suppressed malignant phenotypes in RCC cells, and upregulation of miR-149 exerted a similar effect. Bioinformatics analysis suggested potential binding sites between circ_001504 and miR-149, verified by a dual-luciferase reporter gene assay. Next, we identified nucleobindin 2 (NUCB2), a calcium-binding protein, as a target gene of miR-149. Furthermore, our data suggested that circ_001504 might serve as a competing endogenous RNA of miR-149, serving to elevate the expression of NUCB2. The silencing of circ_001504 resulted in decreased NUCB2 expression, which could be reversed by miR-149 inhibition. In addition, in vivo experiments demonstrated that circ_001504 depletion could suppress tumor growth in an established mouse RCC model. Collectively, reduced expression of circ_001504 lowered NUCB2 expression by sponging miR-149, thereby attenuating RCC progression, providing insight into circ_001504/miR-149/NUCB2 feedback loop into RCC treatment.

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Fig. 1: Upregulation of circ_001504 in RCC tissue and cells.
Fig. 2: Downregulation of circ_001504 contributes to inhibition of cell proliferation, migration, and invasion in RCC.
Fig. 3: The proliferation, migration, and invasion of RCC cells are inhibited while cell cycle and apoptosis are potentiated by overexpression of miR-149.
Fig. 4: circ_001504 competitively sponges miR-149, thus further reducing cell proliferation, migration, and invasion but enhancing cell cycle and apoptosis in RCC.
Fig. 5: circ_001504 increases NUCB2 expression by acting as a ceRNA of miR-149.
Fig. 6: Xenograft tumor growth in nude mice in vivo is inhibited by the downregulation of circ_001504.
Fig. 7: The circ_001504 participates progression of RCC by sponging miR-149 and regulating the expression of NUCB2.

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Acknowledgements

We would like to show sincere appreciation to the reviewers for critical comments on this article.

Funding

The study was supported by Project of Jilin Provincial Finance Department (No. 2019SCZT084).

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Authors and Affiliations

  1. Jilin University, 130000, Changchun, P. R. China

    Rui Xin, Danhua Qu, Huiying Xu & Dawei Chen

  2. Department of Radiology, the Second Hospital of Jilin University, 130000, Changchun, P. R. China

    Rui Xin

  3. Department of Respiratory and Critical Diseases, the Second Hospital of Jilin University, 130000, Changchun, P. R. China

    Danhua Qu

  4. Department of Ultrasound, the First Hospital of Jilin University, 130000, Changchun, P. R. China

    Huiying Xu

  5. Department of Radiation Protection, School of Public Health, Jilin University, 130000, Changchun, P. R. China

    Dawei Chen

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Contributions

RX and DQ designed the study. HX collated the data, DC carried out data analyses and produced the initial draft of the paper. RX contributed to drafting the paper. All authors have read and approved the final submitted paper.

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Correspondence to Dawei Chen.

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This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1038/s41417-023-00630-1

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Xin, R., Qu, D., Xu, H. et al. RETRACTED ARTICLE: circ_001504 promotes the development of renal cell carcinoma by sponging microRNA-149 to increase NUCB2. Cancer Gene Ther 28, 667–678 (2021). https://doi.org/10.1038/s41417-020-00247-8

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