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FOXC2-AS1 stabilizes FOXC2 mRNA via association with NSUN2 in gastric cancer cells

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Abstract

Long noncoding RNA (lncRNA) FOXC2-AS1 has been reported to act as an oncogene in multiple human cancers. However, the clinical significance, functional role and underlying mechanism of FOXC2-AS1 in gastric cancer (GC) remains largely unknown. Here, we found that FOXC2-AS1 expression was significantly elevated in GC tissues and cells, and overexpression of FOXC2-AS1 indicated advanced TNM stage and shorter overall survival in GC patients. Functionally, knockdown of FOXC2-AS1 attenuated the proliferation, migration and invasion of GC cells, whereas overexpression of FOXC2-AS1 showed the opposite effects. Further investigation revealed that FOXC2-AS1 interacted with FOXC2 mRNA and repressed its degradation. FOXC2-AS1 recruited RNA methyltransferase NSUN2 to FOXC2 mRNA, increasing its m5C level and association with YBX1. Taken together, our findings suggested that FOXC2-AS1 acted as an oncogenic lncRNA by stabilizing FOXC2 mRNA in an m5C-dependent manner, which may provide a novel therapeutic target for GC.

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Acknowledgements

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Funding

This study was supported by the Natural Science Foundation of Hanchuan (No. 2018–10-13-54HC).

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Author notes

  1. Jijun Yan and Juntao Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Hanchuan People’s Hospital, Hanchuan, 431600, Hubei Province, China

    Jijun Yan, Juntao Liu, Zhengbin Huang, Wenwei Huang & Jianfa Lv

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  1. Jijun Yan
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All experiments were carried out by all authors. JL designed this research and wrote the manuscript. All authors approved the submission of this manuscript.

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Correspondence to Jianfa Lv.

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This work was approved by the Ethics Committee of Hanchuan People’s Hospital in accordance with the Declaration of Helsinki (approval number: 2020-05-01-143GP).

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Yan, J., Liu, J., Huang, Z. et al. FOXC2-AS1 stabilizes FOXC2 mRNA via association with NSUN2 in gastric cancer cells. Human Cell 34, 1755–1764 (2021). https://doi.org/10.1007/s13577-021-00583-3

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  • DOI: https://doi.org/10.1007/s13577-021-00583-3

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