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miR-211-3p enhances induction chemotherapy insensitivity by upregulating CSF2/CCL20/TNF signaling in hypopharyngeal squamous cell carcinoma

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Abstract

Purpose

To investigate the potential mechanisms of miR-211-3p on induction chemotherapy (IC) sensitivity in hypopharyngeal squamous cell carcinoma (HSCC).

Methods

qRT-PCR was assessed to compare the miR-211-3p expression between IC sensitive and insensitive tumor tissues. The MTT assay was performed to analyze cell proliferation and viability to paclitaxel after alteration of miR-211-3p. Flow cytometry assay was conducted to explore cell apoptosis. Transwell assay was used to explore the effect of miR-211-3p on cell migration. Transcriptome sequencing was then performed to select differentially expressed genes (DEGs) after over-expression of miR-211-3p. GO and KEGG enrichment analyses were conducted to annotate DEGs. PPI analysis was conducted to screen candidate genes. The differential expression and survival status of candidate genes were further validated in TCGA-HNSCC data. The single sample GSEA method was used to investigate the association between downstream genes and immune cell infiltration.

Results

miR-211-3p was up-regulated in IC insensitive larynx–hypopharyngeal tumor tissues. Over-expression of miR-211-3p promoted cell proliferation and migration, and inhibited apoptosis.

The IC50 value of miR-211-3p overexpression (OE) group was significantly higher than negative control (NC) group treated with paclitaxel, suggesting miR-211-3p enhanced IC insensitivity in HSCC. We found 778 DEG after over-expression of miR-211-3p and 11 significant genes were then identified. Finally, colony stimulating factor 2 (CSF2) and C-C motif chemokine ligand 20 (CCL20) were validated to be significantly high expressed and associated with poorer overall survival in head and neck squamous cell carcinoma, which were involved in TNF signaling pathway and then regulated immune cell infiltration.

Conclusion

The miR-211-3p could promote HSCC progression and upregulate CSF2/CCL20/TNF signaling to promote IC insensitivity in HSCC, which may provide new ideas for HSCC therapy.

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Data availability

The datasets generated during and/or analysed during the current study are not publicly available due to the raw data also forms part of an ongoing study, but are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all individuals who take part in this research.

Funding

This project was supported and funded by Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ201910025034); Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20180202); National Key R&D Program of China (2020YFB1312805); National Natural Science Foundation of China (82002880); Beijing Municipal Administration of Hospitals Incubating Program (PX2021008); and Beijing Hospitals Authority Youth Programme (QML20200205).

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Author notes

  1. First Author: Lingwa Wang and Ru Wang.

  2. Lingwa Wang and Ru Wang contributed equally to this article.

Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China

    Lingwa Wang, Ru Wang, Yifan Yang, Ling Feng & Jugao Fang

  2. Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China

    Tianqiao Huang

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  1. Lingwa Wang
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by LW, RW and TH. The first draft of the manuscript was written by LW, RW and JF, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ling Feng or Jugao Fang.

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Financial interests: all authors declare they have no financial interests. The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Wang, L., Wang, R., Huang, T. et al. miR-211-3p enhances induction chemotherapy insensitivity by upregulating CSF2/CCL20/TNF signaling in hypopharyngeal squamous cell carcinoma. Mol Biol Rep 49, 6103–6112 (2022). https://doi.org/10.1007/s11033-022-07401-5

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