LncRNA HAGLROS contribute to papillary thyroid cancer progression by modulating miR-206/HMGA2 expression

Aging (Albany NY). 2023 Dec 18;15(24):14930-14944. doi: 10.18632/aging.205321. Epub 2023 Dec 18.

Abstract

Objective: Papillary thyroid cancer (PTC) is one of the most serious diseases of the endocrine system. In view of the limited therapeutic effects of current medical methods, this study starts from the molecular level and looks for potential treatments. The interaction between HAGLROS/miR-206/HMGA2 was studied using multi-omics methods, which provided new ideas and methods for future treatments.

Method: Microarray analysis and R language were used for differential analysis to screening experimental targets of lncRNA, miRNA, and mRNA. qRT-PCR was used to detect RNA expression in tissues and cells. Double luciferase reporter assays analyzed and validated binding relationships between different RNAs. Colony formation, flow cytometry, and transwell assays were used to measure the effect of them on cell proliferation, apoptosis, and migration.

Result: Microarray analysis identified lncRNAs, miRNAs, and mRNAs differentially expressed in PTC and normal cells, and selected lncRNA HAGLROS, miR-206, and mRNA HMGA2 as study subjects. LncRNA HAGLROS and mRNA HMGA2 were highly expressed in PTC cells while miR-206 was lowly expressed in PTC cells. LncRNA HAGLROS/HMGA2 can inhibit apoptosis of PTC cells, promote proliferation and migration, and miR-206 promotes the above process. HAGLROS and HMGA2 were negatively correlated with miR-206. shHAGLROS promoted miR-206 expression, inhibited HMGA2 expression and repressed PTC tumor growth in mice.

Conclusions: HAGLROS promotes the growth of PTC by competitively binding to miR-206 to promote HMGA2 expression.

Keywords: HAGLROS; HMGA2; miR-206; papillary thyroid cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • HMGA2 Protein* / genetics
  • HMGA2 Protein* / metabolism
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Messenger
  • Thyroid Cancer, Papillary* / genetics
  • Thyroid Cancer, Papillary* / pathology
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / pathology

Substances

  • MicroRNAs
  • MIRN206 microRNA, human
  • RNA, Long Noncoding
  • RNA, Messenger
  • HMGA2 Protein