EIF4A3-Induced Circ_0092278 Enhances Papillary Thyroid Cancer Cell Malignancy by the PI3K/Akt/mTOR Signaling Pathway

J Microbiol Biotechnol. 2025 Jun 19:35:e2501010. doi: 10.4014/jmb.2501.01010.

Abstract

Circular RNA (circRNA) plays a regulatory role in cancer progression, but the role of circ_0092278 in papillary thyroid cancer (PTC) is unclear. In this research, we aimed to reveal the effect of circ_0092278 on PTC progression as well as its interaction with the eukaryotic translation initiation factor 4A3 (EIF4A3). The expression of circ_0092278 in PTC samples was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Cell experiments were conducted to assess the effects of circ_0092278 on PTC cell viability, migration, and invasion. Furthermore, key proteins involved in the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway were examined using western blotting. Additionally, a xenograft model in nude mice was used to investigate the in vivo role of circ_ 0092278. The interactions between EIF4A3 and circ_0092278 were analyzed through RNA-binding protein immunoprecipitation and qRT-PCR assays. Circ_0092278, located in the cell cytoplasm, was significantly upregulated in PTC. Knockdown of circ_0092278 reduced PTC cell proliferation, migration, invasion, and tumor growth by inhibiting the PI3K/Akt/mTOR pathway. Conversely, overexpression of circ_0092278 prompted PTC cell malignancy by activating the PI3K/Akt/mTOR pathway. Additionally, EIF4A3 was found to bind to MINK1 (circ_0092278 linear gene), thereby enhancing the expression of circ_0092278. Circ_0092278, controlled by EIF4A3, promotes PTC progression by activating the PI3K/Akt/mTOR pathway. Our findings indicate that targeting the EIF4A3-circ_0092278 axis may provide a novel approach for treating PTC.

Keywords: EIF4A3; PI3K/Akt/mTOR; circ_0092278; papillary thyroid cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DEAD-box RNA Helicases
  • Eukaryotic Initiation Factor-4A* / genetics
  • Eukaryotic Initiation Factor-4A* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt* / genetics
  • Proto-Oncogene Proteins c-akt* / metabolism
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases* / genetics
  • TOR Serine-Threonine Kinases* / metabolism
  • Thyroid Cancer, Papillary* / genetics
  • Thyroid Cancer, Papillary* / metabolism
  • Thyroid Cancer, Papillary* / pathology
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / metabolism
  • Thyroid Neoplasms* / pathology

Substances

  • RNA, Circular
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Eukaryotic Initiation Factor-4A
  • MTOR protein, human
  • EIF4A3 protein, human
  • Phosphatidylinositol 3-Kinases
  • DEAD-box RNA Helicases