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Long non-coding RNA NRSN2-AS1, transcribed by SOX2, promotes progression of esophageal squamous cell carcinoma by regulating the ubiquitin-degradation of PGK1

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Abstract

Aberrant expression of long non-coding RNAs (lncRNAs) plays pivotal roles in tumorigenesis of human malignant cancers, including esophageal squamous cell carcinoma (ESCC). However, the specific role of lncRNA NRSN2-AS1 in ESCC has not been investigated. Our analysis of clinical data revealed that NRSN2-AS1 was upregulated in ESCC tissues and negatively correlated with patient survival. Luciferase reporter assays and chromatin immunoprecipitation assays demonstrated that NRSN2-AS1 is transcribed by SOX2. In vitro functional experiments showed that NRSN2-AS1 can promote ESCC cell proliferation, migration, and invasion. Furthermore, NRSN2-AS1-binding proteins were detected using RNA pull-down assays and mass spectrometry. Mechanistically, NRSN2-AS1 can bind to phosphoglycerate kinase 1 (PGK1) and upregulate its protein levels by inhibiting its ubiquitination. Knockdown of PGK1 in part abolished the NRSN2-AS1 overexpression-induced effects on ESCC cell proliferation, migration, invasion, and epithelial‑mesenchymal transition (EMT). Thus, NRSN2-AS1 may be a diagnostic biomarker or treatment target for ESCC.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by Grants from the National Natural Science Foundation of China (No. 81772612), Natural Science Foundation of Hebei Province (No. H2020206363, No. 2021206259).

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Authors and Affiliations

  1. Department of CT&MRI, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

    Tongxin Xu

  2. Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

    Zhaoyang Yan

  3. Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Jiankang Rd. 12, Shijiazhuang, 050011, Hebei, China

    Juntao Lu, Liying Chen, Xiaoxu Li, Yan Li, Zhiming Dong & Wei Guo

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  1. Tongxin Xu
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  2. Zhaoyang Yan
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  4. Liying Chen
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  5. Xiaoxu Li
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  6. Yan Li
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  7. Zhiming Dong
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  8. Wei Guo
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by TX, ZY and JL. Figures and tables were prepared by LC, XL and YL. ZD recruited the patients and assisted the experiments. WG applied for Research Ethics Board approval. TX and WG wrote the manuscript and all authors approved the final manuscript.

Corresponding author

Correspondence to Wei Guo.

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Conflict of interest

All authors are in agreement with the content of the manuscript and have no conflict of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Fourth Hospital, Hebei Medical University and informed consent was obtained from all recruited subjects.

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Supplementary file1 (DOCX 21 KB)

10585_2022_10174_MOESM2_ESM.tif

Supplementary file2 (TIF 6043 KB) Fig. S1 Overexpression of NRSN2-AS1 promotes the proliferation, migration, and invasion of ESCC cells in vitro. A evaluation of NRSN2-AS1 overexpression in KYSE170 and ECA109 cells by qRT-PCR after transfection with an NRSN2-AS1 plasmid. B cell proliferation was analyzed by MTS in KYSE170 and ECA109 cells. C–D clone formation assays were conducted in KYSE170 and ECA109 cells. E-F. Cell migration and invasion were determined by transwell assays in KYSE170 and ECA109 cells (**P<0.01)

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Xu, T., Yan, Z., Lu, J. et al. Long non-coding RNA NRSN2-AS1, transcribed by SOX2, promotes progression of esophageal squamous cell carcinoma by regulating the ubiquitin-degradation of PGK1. Clin Exp Metastasis 39, 757–769 (2022). https://doi.org/10.1007/s10585-022-10174-7

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  • DOI: https://doi.org/10.1007/s10585-022-10174-7

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