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

TL;DR

This study shows that a specific circular RNA, circ_0092278, promotes thyroid cancer growth by interacting with a protein called EIF4A3 and activating a key cancer-related signaling pathway.

Contribution

The study identifies a novel regulatory axis involving EIF4A3 and circ_0092278 in papillary thyroid cancer progression.

Findings

Circ_0092278 is upregulated in papillary thyroid cancer and promotes cancer cell proliferation and invasion.

EIF4A3 binds to and enhances the expression of circ_0092278.

The EIF4A3-circ_0092278 axis activates the PI3K/Akt/mTOR pathway to drive cancer progression.

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.

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