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The role of circular RNA during the urological cancer metastasis: exploring regulatory mechanisms and potential therapeutic targets

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Abstract

Metastasis is a major contributor to treatment failure and death in urological cancers, representing an important biomedical challenge at present. Metastases form as a result of cancer cells leaving the primary site, entering the vasculature and lymphatic vessels, and colonizing clones elsewhere in the body. However, the specific regulatory mechanisms of action underlying the metastatic process of urological cancers remain incompletely elucidated. With the deepening of research, circular RNAs (circRNAs) have been found to not only play a significant role in tumor progression and prognosis but also show aberrant expression in various tumor metastases, consequently impacting tumor metastasis through multiple pathways. Therefore, circRNAs are emerging as potential tumor markers and treatment targets. This review summarizes the research progress on elucidating how circRNAs regulate the urological cancer invasion-metastasis cascade response and related processes, as well as their role in immune microenvironment remodeling and circRNA vaccines. This body of work highlights circRNA regulation as an emerging therapeutic target for urological cancers, which should motivate further specific research in this regard.

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Data Availability

No datasets were generated or analysed during the current study.

Abbreviations

CircRNA:

Circular RNA

ccRCC:

Clear cell renal cell carcinoma

RCC:

Renal cell carcinoma

BCa:

Bladder cancer

NcRNA:

Non-coding RNA

LncRNA:

Long-stranded non-coding RNA

EcircRNA:

Exon circRNA

EIcircRNA:

Exon-intron circRNA

CiRNA:

Circular intronic RNA

TricRNA:

tRNA intronic circular RNA

RBP:

RNA-binding proteins

miRNA:

microRNA

AR:

Androgen receptor

U1 snRNPs:

U1 small nuclear ribonucleoproteins

m6A:

N6-methyladenosine

EMT:

Epithelial-mesenchymal transition

CRPC:

Castration-resistant prostate cancer

OS:

Overall survival

MIBC:

Muscle-invasive bladder cancer

DFS:

Disease-free survival

AON:

Antisense oligonucleotides

pre-mRNAs:

precursor mRNAs

CSC:

Cancer stem cell

ACC:

Adrenocortical carcinoma

HPV:

Human papillomavirus

HIF-2:

Hypoxia-inducible factor 2

ceRNA:

Competing endogenous RNA

TFs:

Transcription factors

ADT:

Anti-androgen therapy

CRISPR:

Clustered regularly interspaced short palindromic repeat

EGR1:

Early growth response factor 1

EMT:

Epithelial–mesenchymal transition

FGFR2:

Fibroblast growth factor receptor 2

HNRNPL:

Heterogeneous nuclear ribonucleoprotein L

IGF2BP1:

Insulin-like growth factor 2 mRNA-binding protein 1

MMP:

Matrix metalloproteinase

siRNA:

Small interfering RNA

STAT3:

Signal transducer and activator of transcription 3

TF:

Transcription factor

TIMP-3:

Tissue inhibitor of matrix metalloproteinase-3

UTR:

Untranslated region

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Acknowledgements

This work was supported in part by the National Natural Science Foundation of China (grants 81672523), Xisike-Pilot Cancer Research Foundation (grants 20201030), and Applied Basic Research Program of Liaoning Province in 2023 (grants 2023010409133159830).

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  1. Yan Xu and Zhipeng Gao contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, China

    Yan Xu, Zhipeng Gao, Jun Li, Du Shi & Yuyan Zhu

  2. Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110001, China

    Xiaoyu Sun

  3. Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba, Japan

    Toshinori Ozaki

  4. Department of Laboratory Animal Science, China Medical University, No. 77 Puhe Road, Shenyang, 110122, Liaoning, China

    Meng Yu

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The work presented here was carried out in collaboration with all authors. YYZ identified the topic of the review and directed the completion of the article. YX, JL, and MY conceived the structure of the article; YX, ZPG, XYS, and DS drafted the original draft; YX, TO, and YYZ revised the article. All of the authors had participated in the preparation of this article.

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Xu, Y., Gao, Z., Sun, X. et al. The role of circular RNA during the urological cancer metastasis: exploring regulatory mechanisms and potential therapeutic targets. Cancer Metastasis Rev (2024). https://doi.org/10.1007/s10555-024-10182-x

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