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

  • 0Department of Endocrinology, the First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou, China.

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Summary

This summary is machine-generated.

Hypoxia activates HOTAIR, which upregulates exosomal miR-181a by binding RELA. This exosomal miR-181a promotes papillary thyroid carcinoma angiogenesis by downregulating GATA6.

Area Of Science

  • Molecular Biology
  • Oncology
  • Cell Biology

Background

  • Papillary thyroid carcinoma (PTC) is a common thyroid cancer subtype.
  • Exosomal microRNA-181a (miR-181a) is implicated in PTC development.
  • This study investigates hypoxia's regulation of miR-181a and its role in angiogenesis.

Purpose Of The Study

  • To elucidate the regulatory mechanism of miR-181a under hypoxia.
  • To determine the impact of exosomal miR-181a on tumor angiogenesis.
  • To identify key molecular players in this pathway.

Main Methods

  • Ribonucleoprotein immunoprecipitation (RIP) and Chromatin Immunoprecipitation (ChIP-qPCR) to assess molecular interactions.
  • Short hairpin RNA (shRNA) for gene knockdown and rescue experiments.
  • Dual-luciferase assays to confirm promoter activity and functional assays (CCK8, EdU, Transwell, Western Blot) to evaluate angiogenesis and cell behavior.

Main Results

  • HOTAIR binds RELA under hypoxia, leading to RELA-mediated upregulation of miR-181a.
  • HOTAIR knockdown reduces miR-181a levels, which can be restored by RELA overexpression.
  • Exosomal miR-181a downregulates GATA6, inhibiting HUVEC proliferation, migration, and tube formation, while also reducing EGFR expression.

Conclusions

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

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