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LncRNA MAFG-AS1 promotes the malignant phenotype of ovarian cancer by upregulating NFKB1-dependent IGF1

Cancer Gene Therapy volume 29, pages 277–291 (2022)Cite this article

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Abstract

Long non-coding RNAs (lncRNAs) were recently recognized to vitally function in a variety of cancer cellular events, including epithelial-mesenchymal transition (EMT), invasion, and migration, particularly in ovarian cancer (OC). Herein, we sought to investigate the potential role of MAFG-AS1 in the malignant behaviors of OC cells. The binding affinity between MAFG-AS1, miR-339-5p, NFKB1 or IGF1 was characterized so as to identify the underlying mechanism of corresponding their interactions. We conducted MAFG-AS1 overexpression or knockdown along with NFKB1 and IGF1 silencing to examine their effects on the EMT, migration, and invasion of OC cells. Tumors were xenografted in nude mice to validate the in vitro findings. Our data showed significantly high expression pattern of MAFG-AS1 in the OC tissues and cells. Further mechanistic investigations revealed that MAFG-AS1 upregulated the IGF1 expression pattern through recruitment of NFKB1, whereas MAFG-AS1 upregulated the NFKB1 expression pattern through binding to miR-339-5p. Thus, MAFG-AS1 overexpression accelerated the EMT, invasion, and migration of OC cells, which could be annulled by silencing of IGF1 or NFKB1. Besides, our in vitro findings were successfully recapitulated in the xenograft mice. These results determined that MAFG-AS1 stimulated the OC malignant progression by upregulating the NFKB1-mediated IGF1 via miR-339-5p, thus highlighting a novel potential therapeutic target against OC.

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Fig. 1: MAFG-AS1 is highly expressed in OC tissues.
Fig. 2: MAFG-AS1 knockdown suppresses the EMT, invasion, and migration in OC.
Fig. 3: MAFG-AS1 enhances the EMT, invasion, and migration of OC cells by recruiting NFKB1.
Fig. 4: MAFG-AS1 upregulates NFKB1 expression pattern via competitive binding with miR-339-5p.
Fig. 5: MAFG-AS1 elevates the expression pattern of IGF1 through NFKB1.
Fig. 6: MAFG-AS1 facilitates the EMT, invasion, and migration of OC cells via elevation of the expression of IGF1.
Fig. 7: Silencing of MAFG-AS1 or IGF1 in vivo delays tumor growth in nude mice.
Fig. 8: Schematic representation and function of MAFG-AS1 in malignant behaviors of OC cells.

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Acknowledgements

We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.

Funding

This study was supported by the Henan Medical Science and Technology Program (201602381) and Henan Science and Technology Research Project of Henan Province Department of Science and Technology (172102310168).

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  1. These authors contributed equally: Yang Bai, Chenchen Ren

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P.R. China

    Yang Bai, Chenchen Ren, Baojin Wang, Jingge Xue, Feiyan Li, Jiaxi Liu & Li Yang

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Contributions

YB, CCR, and BJW designed the study. YB, JGX, and FYL collated the data, carried out data analyses and produced the initial draft of the manuscript. JXL, and LY contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

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Correspondence to Li Yang.

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Bai, Y., Ren, C., Wang, B. et al. LncRNA MAFG-AS1 promotes the malignant phenotype of ovarian cancer by upregulating NFKB1-dependent IGF1. Cancer Gene Ther 29, 277–291 (2022). https://doi.org/10.1038/s41417-021-00306-8

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