Circular RNAs in renal cell carcinoma: implications for tumorigenesis, diagnosis, and therapy
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REVIEW
Open Access
Circular RNAs in renal cell carcinoma: implications for tumorigenesis, diagnosis, and therapy Ying Wang1, Yunjing Zhang1, Ping Wang2*, Xianghui Fu3* and Weiqiang Lin1*
Abstract Renal cell carcinoma (RCC) is the most common malignant kidney tumor and has a high incidence rate. Circular RNAs (circRNAs) are noncoding RNAs with widespread distribution and diverse cellular functions. They are highly stable and have organ- and tissue-specific expression patterns. CircRNAs have essential functions as microRNA sponges, RNA-binding protein- and transcriptional regulators, and protein translation templates. Recent reports have shown that circRNAs are abnormally expressed in RCC and act as important regulators of RCC carcinogenesis and progression. Moreover, circRNAs have emerged as potential biomarkers for RCC diagnosis and prognosis and targets for developing new treatments. However, further studies are needed to better understand the functions of circRNAs in RCC. In this review, we summarize and discuss the recent research progress on RCC-associated circRNAs, with a focus on their potential for RCC diagnosis and targeted therapy. Keywords: CircRNA, Renal cell carcinoma, Biomarker, Targeted therapy
Background Renal cell carcinoma (RCC), the most common kidney neoplasm, originates in renal tubular epithelial cells and accounts for 85–90% of adult renal malignancies [1]. RCC is the sixth- and eight-most common cancer in males and females, and it is estimated that there will be 73,750 new cases of RCC in 2020 in the US [2]. RCC diagnoses have been increasing in recent years, mainly due to improvements in imaging techniques and ultrasonography [3, 4]. Currently, surgical resection is the first-line treatment for RCC. However, local recurrence * Correspondence: [email protected]; [email protected]; [email protected] 2 Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China 3 Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, Sichuan, China 1 Kidney Disease Center, The Fourth Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Jinhua 322000, Zhejiang, China
or distant metastasis still occur in some patients even after radical nephrectomy. Moreover, the majority of RCCs are resistant to chemotherapy and radiotherapy once they recur or metastasize [5–7]. Although targeted therapies have significantly improved therapeutic outcomes for advanced RCC patients, their effectiveness is still limited. Cancer recurrence, metastasis, and resistance to therapy affect the recovery of patients with RCC [8–13]. Therefore, the early detection of postoperative micrometastases and recurrent lesions, and overcoming RCC drug resistance can improve patient prognosis. RCC tumorigenesis is an extremely complex process that involves genetic mutations and the dysregulation of
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