Open Access

ARTICLE

Circ_0053943 complexed with IGF2BP3 drives uveal melanoma progression via regulating N6-methyladenosine modification of Epidermal growth factor receptor

ANDI ZHAO^1,2,#, YUE WANG^3,#, ZIJIN WANG^1,2, QING SHAO^1,2, QI GONG^1,2, HUI ZHU^1,2, SHIYA SHEN^1,2, HU LIU^1,2,*, XUEJUAN CHEN^1,2,*

1 Department of Ophthalmology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China
2 The First Clinical Medical College, Nanjing Medical University, Nanjing, 211166, China
3 Department of Ophthalmology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China

* Corresponding Authors: HU LIU. Email: ; XUEJUAN CHEN. Email:
# These authors contributed equally to this paper

(This article belongs to the Special Issue: Non-coding RNAs on the Clinical Application of Solid Cancers)

Oncology Research 2024, 32(5), 983-998. https://doi.org/10.32604/or.2024.045972

Received 13 September 2023; Accepted 22 December 2023; Issue published 23 April 2024

Abstract

Numerous studies have characterized the critical role of circular RNAs (circRNAs) as regulatory factors in the progression of multiple cancers. However, the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma (UM) remain enigmatic. In this study, we identified a novel circRNA, circ_0053943, through re-analysis of UM microarray data and quantitative RT-PCR. Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings. Mechanistically, circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA. RNA sequencing assays identified epidermal growth factor receptor (EGFR) as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level. Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Collectively, circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex, thus providing a potential biomarker and therapeutic target for UM.

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Supplementary Material

Supplementary Material File

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