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HYPOXIA induces lncRNA HOTAIR for recruiting RELA in papillary thyroid cancer cells to upregulate miR-181a and promote angiogenesis

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Abstract

Background

Papillary thyroid carcinoma (PTC) is one of the most common subtypes of thyroid carcinoma. Exosomal miR-181a plays an important role in the development of PTC. This study examined the regulatory mechanism of miR-181a under conditions of hypoxia and its impact on angiogenesis.

Methods

A ribonucleoprotein immunoprecipitation (RIP) experiment was conducted to verify the interaction between HOTAIR and RELA. The relationship between RELA and the miR-181a promoter was detected by ChIP-qPCR. Short hairpin (sh) RNA was designed to knock down HOTAIR in TPC cells. The underlying mechanism of miR-181a was verified by use of dual-luciferase assays and rescue experiments. The regulatory effect of GATA6 on angiogenesis was studied using CCK8, EdU, Transwell, and western blot assays.

Results

A RIP assay showed that HOTAIR could bind to RELA under hypoxic conditions. ChIP-qPCR and dual luciferase assays showed RELA could interact with the miR181a promoter and upregulate miR-181a. Knockdown of HOTAIR downregulated miR-181a in TPC-1 cells, and the downregulation could be rescued by RELA overexpression. MiR-181a downregulated GATA6 in HUVEC cells. Overexpression of GATA6 inhibited HUVEC proliferation, migration, tube formation, and EGFR expression. Exosomal miR-181a promoted angiogenesis by downregulating GATA6 expression.

Conclusion

HOTAIR activated RELA to upregulate miR-181a during hypoxia. Exosomal miR-181a promotes tumor angiogenesis by downregulating GATA6.

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Data availability

The datasets generated and analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Funding

This study was supported by the Science and Technology Projects in Guangzhou (No. 202102010081).

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Author notes

  1. J. Lu and X. Liu these authors contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, the First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou, China

    J. Lu, X. Liu & Y. Wang

  2. Department of Endocrinology, the People’s Hospital of Jiangmen, Jiangmen, Guangdong, China

    A. Cen

  3. Department of Endocrinology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China

    Y. Hong

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Contributions

Yingxue Wang conceived and designed the experiments. Jieying Lu, Xinyi Liu performed the experiments. Aiying Cen and Yuanjia Hong analyzed the data. Yingxue Wang wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Y. Wang.

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Lu, J., Liu, X., Cen, A. et al. HYPOXIA induces lncRNA HOTAIR for recruiting RELA in papillary thyroid cancer cells to upregulate miR-181a and promote angiogenesis. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-024-02388-1

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