Abstract
Simple SummaryDrug resistance to systematic treatment in genitourinary tumors severely aggravated the burden on patients and society. Multiple mechanisms were involved in drug resistance. As typical non-coding RNAs, circRNAs play a critical role in the onset and development of cancers and several studies implied their function in the regulation of drug resistance. Here, we reviewed the investigations of circRNAs’ behavior in drug resistance of genitourinary cancers and summarized the underlying mechanisms. This review emphasized the essential role of circRNAs in drug resistance development and also pointed out the potential topics that need further investigations in the future.In recent years, systematic treatment has made great progress in genitourinary tumors. However, some patients develop resistance to the treatments, resulting in an increase in mortality. Circular RNAs (circRNAs) form a class of non-coding RNAs with high stability and significant clinical relevance. Accumulating evidence indicates that circRNAs play a vital role in cancer development and tumor chemotherapy resistance. This review summarizes the molecular and cellular mechanisms of drug resistance mediated by circRNAs to common drugs used in the treatment of genitourinary tumors. Several circRNAs were identified to regulate the responsiveness to systemic treatments in genitourinary tumors, including chemotherapies such as cisplatin and targeted therapies such as enzalutamide. Canonically, cicrRNAs participate in the competing endogenous RNA (ceRNA) network, or in some cases directly interact with proteins, regulate downstream pathways, and even some circRNAs have the potential to produce proteins or polypeptides. Several cellular mechanisms were involved in circRNA-dependent drug resistance, including autophagy, cancer stem cells, epithelial-mesenchymal transition, and exosomes. The potential clinical prospect of circRNAs in regulating tumor drug resistance was also discussed.
Highlights
Genitourinary cancers, including renal cell carcinoma (RCC), bladder cancer (BCa), prostate cancer (PCa), and other less common cancers, were estimated to have 362,860 newly diagnosed cases and lead to 68,030 deaths in the United States in 2020 [1]; especially since PCa has the greatest number of new cases and the 2nd greatest number of deaths in men, and BCa ranked 4th in new cases and 8th in deaths in men
Huang et al found that the expression of cicrSNX6 was upregulated in sunitinib-resistant renal cancer cell lines by RNA-seq, and verified that circSNX6 can sponge miR-1184 and inhibit Glycerophosphocholine Phosphodiesterase 1 (GPCPD1), and increased the content of Lysophosphatidic Acid (LPA) in cells, which eventually led to the enhancement of drug resistance of renal cancer cells to sunitinib [51]
Based on the depth of BCa invasion, BCa could be divided into non-muscular invasive BCa (NMIBC) and muscular invasive BCa (MIBC) and more than two-thirds of BCa belong to NMIBC [53]
Summary
Genitourinary cancers, including renal cell carcinoma (RCC), bladder cancer (BCa), prostate cancer (PCa), and other less common cancers, were estimated to have 362,860 newly diagnosed cases and lead to 68,030 deaths in the United States in 2020 [1]; especially since PCa has the greatest number of new cases and the 2nd greatest number of deaths in men, and BCa ranked 4th in new cases and 8th in deaths in men. Radical treatments with curative purposes were recommended for early-stage cancers, such as radical and partial nephrectomy for RCC [2], transurethral resection of bladder tumors and radical cystectomy for BCa [3,4], as well as radical prostatectomy (RP) and radical radiation therapy (RT). Cancers 2022, 14, x Cancers 2022, 14, 866 nephrectomy for RCC [2], transurethral resection of bladder tumors and radical cy2sotfe2c0tomy for BCa [3,4], as well as radical prostatectomy (RP) and radical radiation therapy (RT) for PCa [5], but when the cancers progressed to advanced or even metastatic stages, the cancers are no longer curable by surgical treatments and systemic therapy would be ftohrePpCriam[5a]r,ybcuhtowicheetnhtahteccoaunldceersffepcrtoivgerelysseexdtetondadsvuarnvciveadl o[r6–e8v]e. With the rapid development of high-throughput sequencing technologies and novel approaches of functional characterization, the identification and relevant mechanisms of circRNAs have been widely explored [15].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
