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RETRACTED ARTICLE: Downregulation of microRNA-324-3p inhibits lung cancer by blocking the NCAM1-MAPK axis through ALX4

Cancer Gene Therapy volume 28, pages 455–470 (2021)Cite this article

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A Retraction to this article was published on 10 June 2021

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Abstract

Lung cancer remains the principal cause of cancer-related death worldwide. As microRNAs (miRNAs) are critically involved in lung cancer, we investigated the potential role of miR-324-3p in lung cancer via the ALX4/NCAM1/MAPK axis. The expression of miR-324-3p and ALX4 was detected in clinical samples, and their interaction confirmed by miRNA-targeted luciferase reporter assay. The mechanisms involved in the miR-324-3p-ALX4 interaction in lung cancer cell biological processes were analyzed through gain- and loss-of function approaches. In addition, cultured lung cancer cells were treated with the p38MAPK pathway activator P79350 in order to explore the role of this pathway in the abovementioned axis. Further, a tumor xenograft model in nude mice was constructed to confirm the in vitro findings. miR-324-3p was highly expressed in lung cancer tissues and cells, and inhibited the expression of ALX4 in A549 cells. After confirming the targeted inhibition of ALX4 by miR-324-3p, we showed that this interaction upregulated the expression of NCAM1 and activated the MAPK pathway. The inhibition of miR-324-3p could suppress lung cancer cell invasion, migration, and autophagy, and retarded the growth of subcutaneous tumors in nude mice. Downregulation of ALX4 or NCAM1 overexpression reversed these favorable effects of decreased miR-324-3p. Our study demonstrated the promotive effect of miR-324-3p on the development and progression of lung cancer, thus suggesting a new target for treatment of this devastating disease.

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Fig. 1: miR-324-3p expression is high in NSCLC tissues and lung cancer cells, and inhibition of miR-324-3p reduces invasion and migration of lung cancer cells and promotes their apoptosis.
Fig. 2: Targeted inhibition of ALX4 expression by miR-324-3p in lung cancer cells.
Fig. 3: miR-324-3p inhibition decreases the progression of lung cancer by upregulating ALX4.
Fig. 4: miR-324-3p inhibition disrupts the NCAM1-MAPK axis by upregulating ALX4 in lung cancer cells.
Fig. 5: miR-324-3p downregulation decreases lung cancer cell migration and invasion but elevates apoptosis by blocking the NCAM1-MAPK axis.
Fig. 6: The targeted inhibition of ALX4 by miR-324-3p promotes autophagy of lung cancer cells.
Fig. 7: miR-324-3p inhibition diminishes lung cancer cell autophagy by inactivating the NCAM1-MAPK axis.
Fig. 8: miR-324-3p downregulation suppresses tumorigenesis of lung cancer cells in vivo by blocking the NCAM1-MAPK axis through ALX4.
Fig. 9: The putative underlying mechanism of miR-324-3p in lung cancer.

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Acknowledgements

This study was supported by Bao’an District Scientific and Technology Innovation Bureau (NO. 2017JD100).

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Authors and Affiliations

  1. Department of Thoracic Surgery, West China Hospital, Sichuan University, 610000, Chengdu, P.R. China

    Tieniu Song

  2. Department of Nephrology (2nd Section), Lanzhou University Second Hospital, 730030, Lanzhou, P.R. China

    Hui Zhou

  3. Department of Thoracic Surgery, Lanzhou University Second Hospital, 730030, Lanzhou, P.R. China

    Xiaoping Wei & Yuqi Meng

  4. Department of Thoracic Surgery, Shenzhen Hospital of Southern Medical University, 518000, Shenzhen, P.R. China

    Quanwei Guo

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  1. Tieniu Song
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Correspondence to Tieniu Song.

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This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1038/s41417-021-00357-x

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Song, T., Zhou, H., Wei, X. et al. RETRACTED ARTICLE: Downregulation of microRNA-324-3p inhibits lung cancer by blocking the NCAM1-MAPK axis through ALX4. Cancer Gene Ther 28, 455–470 (2021). https://doi.org/10.1038/s41417-020-00231-2

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