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RETRACTED ARTICLE: Silencing of long non-coding RNA XIST represses gastric cancer progression through blocking NFκB pathway via inhibiting HNF4A-mediated transcription of EPHA1

Cancer Gene Therapy volume 28, pages 307–320 (2021)Cite this article

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This article was retracted on 12 September 2023

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Abstract

Gastric cancer (GC) is a common cancer and a leading cause of cancer-related deaths worldwide. Recent studies have supported the important role of long non-coding RNAs (lncRNAs) in GC progression. This study identified functional significance of X inactive specific transcript (XIST) in GC. The expression of XIST and EPHA1 in GC tissues and cells was measured. Then, dual luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay and Chromatin Immunoprecipitation (ChIP) assay were performed to explore the interaction among XIST, EPHA1 and HNF4A. The effects of XIST on GG progression were evaluated by determining expression of proliferation- and invasion-related proteins (Ki67, PCNA, MMP-2, and MMP-9). Further, the functional role of XIST in GC with the involvement of NFκB pathway was also analyzed. Subsequently, the tumor growth in nude mice was evaluated. High expression of XIST and EPHA1 was observed in GC. XIST elevated EPHA1 expression by recruiting HNF4A. In addition, silencing of XIST inhibited GC progression in vitro and in vivo. Overexpressed XIST and EPHA1 yielded a reversed effect on cell proliferation and invasion. SN50 treatment (inhibitor of NFκB pathway) counteracted the promotive effect on GC cell proliferation and invasion mediated by XIST. The present study unveils that XIST increases the enrichment of HNF4A in the promoter region of EPHA1, thus promoting the deterioration of GC.

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Fig. 1: The high expression of XIST in GC tissues and cells.
Fig. 2: XIST silencing represses the pathogenesis of GC.
Fig. 3: The expression of EPHA1 is elevated by XIST through recruiting HNF4A.
Fig. 4: Silencing of XIST inhibits the pathogenesis of GC through HNF4A/EPHA1 axis in HS 746T cells.
Fig. 5: XIST/HNF4A/EPHA1 axis mediates the pathogenesis of GC by regulating NFκB pathway.
Fig. 6: XIST represses the progression of GC in vivo through inhibition of NFκB pathway.
Fig. 7: Mechanistic diagram illustrating the XIST/HNF4A/EPHA1 axis in GC.

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Data availability

The datasets generated/analyzed during the current study are available.

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Acknowledgements

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

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Author notes

  1. These authors contributed equally: Ping Li, Liuhua Wang

Authors and Affiliations

  1. Department of Central Laboratory, Huaian Tumor Hospital & Huaian Hospital of Huaian City, Huaian, 223200, PR China

    Ping Li, Pengfei Li & Fangyong Hu

  2. Department of General Surgery, Huaian Tumor Hospital & Huaian Hospital of Huaian City, Huaian, 223200, PR China

    Ping Li, Pengfei Li & Fangyong Hu

  3. Department of Experimental Surgery-Cancer Metastasis, Medical Faculty Mannheim, Ruprecht Karls University, Mannheim, 68167, Germany

    Ping Li & Yi Cao

  4. Department of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Institute of General Surgery-Yangzhou, Yangzhou University, Yangzhou, 225000, PR China

    Liuhua Wang, Dong Tang & Daorong Wang

  5. Department of General Surgery, Jiangdu People’s Hospital of Yangzhou, Yangzhou, 225200, PR China

    Gang Ye & Hongbo Li

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Contributions

Ping Li, LW, Pengfe Li, FH, YC, and DT participated in the conception and design of the study. Ping Li, LW, Pengfe Li, GY, DW, and HL performed the analysis and interpretation of data. Ping Li, LW, GY, DW, and HL contributed to drafting the article. FH, YC, GY, and DW revised it critically for important intellectual content. HL is the GUARANTOR for the article who accepts full responsibility for the work and/or the conduct of the study, had access to the data, and oversaw the decision to publish.

Corresponding author

Correspondence to Hongbo Li.

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The authors declare that they have no conflict of interest.

Ethical approval

The current study was performed with the approval of the ethical committee of Jiangdu People’s Hospital of Yangzhou and written informed consent was obtained from each participant. Animal experiments were conducted in strict accordance with recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

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This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1038/s41417-023-00667-2

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Li, P., Wang, L., Li, P. et al. RETRACTED ARTICLE: Silencing of long non-coding RNA XIST represses gastric cancer progression through blocking NFκB pathway via inhibiting HNF4A-mediated transcription of EPHA1. Cancer Gene Ther 28, 307–320 (2021). https://doi.org/10.1038/s41417-020-00220-5

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