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Kin17 facilitates thyroid cancer cell proliferation, migration, and invasion by activating p38 MAPK signaling pathway

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A Correction to this article was published on 06 January 2021

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Abstract

Kin17 DNA and RNA binding protein (Kin17) is an extremely conserved nuclear protein that is almost expressed in every type of mammal cells. Recently, Kin17 has been implicated into the regulation of tumorigenesis of diverse human cancers. However, its functions in thyroid cancer (TC) are still largely unexplored. Kin17 mRNA and protein level were tested by qRT-PCR and western blot, respectively. Effects of Kin17 on TC cell proliferation were estimated by colony formation assay and flow cytometry analysis in vitro as well as by in vivo tumor growth experiment. TC cell migratory and invasive capacities were assessed via wound-healing and transwell experiments. Epithelial–mesenchymal transition (EMT)-related proteins (E-cadherin and N-cadherin) and p38 MAPAK signaling pathway-related proteins (p-p38, p38, Cyclin D1, and p27) were examined via western blot. Kin17 was remarkably increased in TC tissue samples and cell lines at both mRNA and protein levels compared to normal tissue and control cell line. Knockdown of Kin17 obviously repressed TC cell proliferation, arrested cell cycle, and inhibited TC cell migration and invasion in vitro, while overexpression of Kin17 produced opposite effects. Kin17 knockdown suppressed p38 MAPK signaling pathway, while Kin17 overexpression activated this pathway. Treatment of p38 agonist (p79350) abolished the repressive effects of sh-Kin17 on TC cell proliferation, migration, and invasion, as well as on p38 pathway. Kin17 knockdown was also found to enhance the sensitivity of Doxorubicin of TC cells. In addition, Kin17 knockdown in vivo also markedly repressed TC tumor growth and p38 pathway. Kin17 functioned as an oncogene of TC by activating p38 MAPK signaling pathway.

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Abbreviations

TC:

Thyroid cancer

FTC:

Follicular thyroid cancer

MTC:

Medullary thyroid carcinoma

PDTC:

Poorly differentiated thyroid cancer

ATC:

Anaplastic thyroid cancer

MAPK:

Mitogen-activated protein kinase

NSCLC:

Non-small cell lung cancer

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Funding

This work is supported by the National Natural Science Foundation of China (No. 81660294) and The Youth Fund of Department of Education of Jiangxi Province (No. GJJ180146).

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China

    Qun-Guang Jiang

  2. Department of Thyroid Surgery, The First Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, People’s Republic of China

    Cheng-Feng Xiong & Yun-Xia Lv

Authors
  1. Qun-Guang Jiang
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  3. Yun-Xia Lv
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Contributions

Guarantor of integrity of the entire study: Y-XL; study concepts: Y-XL, Q-GJ; study design: Q-GJ; definition of intellectual content: C-FX; literature research: C-FX; clinical studies: Q-GJ; experimental studies: Y-XL, Q-GJ; data acquisition: Y-XL, Q-GJ; data analysis: C-FX; statistical analysis: Q-GJ; manuscript preparation: C-FX; manuscript editing: Q-GJ; manuscript review: Y-XL.

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Correspondence to Yun-Xia Lv.

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The authors have no commercial or other associations that might pose a conflict of interest.

Ethical approval

Manipulates in this study were approved by the Ethics Committee of The First Affiliated Hospital of NanChang University, and written informed consent was provided to each participant. Human TC cell lines (K1, SW579, 8505C, TPC1, and BCPAP) and human thyroid follicular epithelial cells (Nthy-ori 3–1) were purchased from the American Type Culture Collection (ATCC, USA).

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Jiang, QG., Xiong, CF. & Lv, YX. Kin17 facilitates thyroid cancer cell proliferation, migration, and invasion by activating p38 MAPK signaling pathway. Mol Cell Biochem 476, 727–739 (2021). https://doi.org/10.1007/s11010-020-03939-9

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  • DOI: https://doi.org/10.1007/s11010-020-03939-9

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