J Cancer 2021; 12(5):1295-1306. doi:10.7150/jca.52171

Research Paper

ANXA1 enhances tumor proliferation and migration by regulating epithelial-mesenchymal transition and IL-6/JAK2/STAT3 pathway in papillary thyroid carcinoma

Xin Zhao1*, Weiguo Ma2*, Xinyu Li1, Haijun Li1, Jin Li1, Hongle Li3, Fucheng He1✉

1. Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China
2. Department of Medical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, China
3. Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, China.
* These authors contributed equally to this work.

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Citation:
Zhao X, Ma W, Li X, Li H, Li J, Li H, He F. ANXA1 enhances tumor proliferation and migration by regulating epithelial-mesenchymal transition and IL-6/JAK2/STAT3 pathway in papillary thyroid carcinoma. J Cancer 2021; 12(5):1295-1306. doi:10.7150/jca.52171. Available from https://www.jcancer.org/v12p1295.htm

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Abstract

Background: Annexin A1 (ANXA1) was discovered to show various effects during tumor initiation and development in a tumor-specific manner. However, the function of ANXA1 in papillary thyroid carcinoma (PTC) has not been reported.

Methods: Bioinformatic analyses, RT-PCR and immunohistochemistry were employed to determine the ANXA1 expression level in PTC. Both gain- and loss-of-function studies, including CCK-8, EdU assay, transwell experiment and wound-healing assay were used to investigate the role of ANXA1 in PTC progression. GSEA enrichment analysis was utilized to explore the potential mechanisms of ANXA1 mediated downstream signaling, and ELISA, RT-PCR and western blot were used to confirm the relevance.

Results: ANXA1 expression was prominently upregulated in PTC tumor tissues. Ectopic expression of ANXA1 expedited PTC cell proliferation, migration and invasion, whereas ANXA1 knockdown exhibited the opposing trends. Mechanistic investigations showed that ANXA1 regulated epithelial-mesenchymal transition (EMT) and activated the IL-6/JAK2/STAT3 pathway to contribute to PTC malignant behaviors. In particular, loss of ANXA1 retarded tumor burden and suppressed lung metastasis in vivo.

Conclusions: In conclusion, our findings identified ANXA1 as a pivotal oncogene during PTC carcinogenesis and ANXA1 might function as a promising therapeutic target and prognostic marker for PTC.

Keywords: ANXA1, papillary thyroid cancer, epithelial-mesenchymal transition, IL-6, STAT3