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MiR-221-3p Facilitates Thyroid Cancer Cell Proliferation and Inhibit Apoptosis by Targeting FOXP2 Through Hedgehog Pathway

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Abstract

Thyroid cancer (TC) is most often found in the endocrine system, the incidence of which has been on a continuous increase in recent years. For a better treatment of it, it becomes a pressing matter to further delve into the mechanism of TC onset and progression. FOXP2 is lowly expressed in diverse cancer, which has a deep connection with malignant progression of tumors. However, in TC, studies about this gene are exceedingly limited. In this study, FOXP2 was discovered to be lowly expressed in TC tissues based on the analysis of TCGA database. This finding was further confirmed by the qRT-PCR that FOXP2 was lowly expressed in TC cell lines. The results of a series of cell function assays demonstrated that overexpressed FOXP2 could hamper TC cell proliferation and stemness, facilitate apoptosis, and arrest the cell cycle. For a deep exploration of its mechanism, we mined its upstream factor miR-221-3p with the aid of starBase and mirDIP databases. The dual-luciferase reporter assay was employed to verify the binding relationship between miR-221-3p and FOXP2. Besides, we also discovered the HEDGEHOG pathway existing downstream of FOXP2 by gene set enrichment analysis. Based on these findings, we also performed a rescue experiment, the result of which indicated that the overexpression of FOXP2 was able to reverse the effects of overexpressed miR-221-3p in several cell activities including proliferation, sphere-formation, apoptosis, and cell cycle. Besides, it could also have an impact on the expression of HEDGEHOG pathway-related proteins influenced by overexpressed miR-221-3p. Our study provided the new insights into the mechanism by which miR-221-3p functions in the development of TC.

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Authors and Affiliations

  1. Department of Head and Neck Surgery, Tangshan Gongren Hospital, 27# Wenhua Road, Tangshan, 063000, Hebei Province, China

    Wang Chang, Qing Chang, Haodong Lu, Yanbing Li & Chunyou Chen

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  1. Wang Chang
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  2. Qing Chang
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  3. Haodong Lu
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  4. Yanbing Li
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Contributions

Conceptualization: WC. Data curation: QC, WC, HL. Formal analysis: YL, CC. Methodology: QC, HL. Software: YL, CC. Validation: WC, YL. Investigation: HL. Writing—original draft: WC, YL. Writing—review & editing: CC, HL. All the authors read and approved the final manuscript.

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Correspondence to Chunyou Chen.

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Chang, W., Chang, Q., Lu, H. et al. MiR-221-3p Facilitates Thyroid Cancer Cell Proliferation and Inhibit Apoptosis by Targeting FOXP2 Through Hedgehog Pathway. Mol Biotechnol 64, 919–927 (2022). https://doi.org/10.1007/s12033-022-00473-5

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  • DOI: https://doi.org/10.1007/s12033-022-00473-5

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