scholarly journals CircRNAs: Emerging Bladder Cancer Biomarkers and Targets

2021 ◽  
Vol 10 ◽  
Author(s):  
Zhaofeng Liang ◽  
Wenhao Guo ◽  
Shikun Fang ◽  
Yue Zhang ◽  
Ling Lu ◽  
...  

Circular RNAs (circRNAs) are newly discovered intriguing RNAs due to the covalently closed loop structure, high stability, tissue specificity, and functional diversity. In recent years, a large number of circRNAs have been identified through high-throughput sequencing technology and bioinformatics methods, the abnormal expression of circRNAs are closely related to many diseases including bladder cancer (BC). CircRNAs have been proven to have several functions, such as acting as a regulator of parental gene transcription, miRNA sponge and interacting with proteins to regulate its expression. In addition, some circRNAs have been identified to encode proteins. CircRNAs have the characteristics of high abundance, high stability, wide distribution in body fluids, tissue specificity, and developmental stage specificity, which determine that circRNAs has great potential to be utilized as biomarkers for BC. Herein, we briefly summarize the biogenesis, functions and roles, and the current research progress of circRNAs in BC with a focus on the potential application for BC diagnosis, treatment, and prognosis.

2021 ◽  
Vol 7 (1) ◽  
pp. 2
Author(s):  
Debina Sarkar ◽  
Sarah D. Diermeier

Circular RNAs (circRNAs) are a class of non-coding RNAs that form a covalently closed loop. A number of functions and mechanisms of action for circRNAs have been reported, including as miRNA sponge, exerting transcriptional and translational regulation, interacting with proteins, and coding for peptides. CircRNA dysregulation has also been implicated in many cancers, such as breast cancer. Their relatively high stability and presence in bodily fluids makes cancer-associated circRNAs promising candidates as a new biomarker. In this review, we summarize the research undertaken on circRNAs associated with breast cancer, discuss circRNAs as biomarkers, and present circRNA-based therapeutic approaches.


2021 ◽  
Vol 692 (4) ◽  
pp. 042059
Author(s):  
Yujun Zhang ◽  
Puchang Wang ◽  
Zhongfu Long ◽  
Leilei Ding ◽  
Wen Zhang ◽  
...  

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Chen Yang ◽  
Zezhong Mou ◽  
Siqi Wu ◽  
Yuxi Ou ◽  
Zheyu Zhang ◽  
...  

AbstractBladder cancer (BC) is known as a common and lethal urinary malignancy worldwide. Circular RNAs (circRNAs), an emerging non-coding RNA, participate in carcinogenesis process of several cancers including BC. In this study, high-throughput sequencing and RT-qPCR were applied to discover and validate abnormal high expression of circUBE2K in BC tissues. Fluorescence in situ hybridization (FISH) was used to detect hsa_circ_0009154 (circUBE2K) expression and subcellular localization in BC tissues. High circUBE2K predicted unfavorable prognoses in BCs, as well as correlated with clinical features. CCK8, transwell, EdU and wound healing assays demonstrated down-regulating circUBE2K decreased BC cell phenotype as proliferation, invasion, and migration, respectively. Further studies showed that circUBE2K promoted BC progression via sponging miR-516b-5p and enhancing ARHGAP5 expression through regulating RhoA activity. Dual-luciferase reporter, FISH and RNA pulldown assays were employed to verify the relationships among circUBE2K/miR-516b-5p/ARHGAP5/RhoA axis. Down-regulating miR-516b-5p or overexpressing ARHGAP5 restored RhoA activity mediated BC cell properties after silencing circUBE2K. Subcutaneous xenograft and metastasis model identified circUBE2K significantly increased BC cell metastasis and proliferation in-vivo. Taken together, we found that circUBE2K is a tumor-promoting circRNA in BC that functions as a ceRNA to regulate ARHGAP5 expression via sponging miR-516b-5p.


2020 ◽  
Author(s):  
Mingming Jin ◽  
Shengjie Lu ◽  
Yue Wu ◽  
Chen Yang ◽  
Chunzi Shi ◽  
...  

Abstract Background: Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in the cancer developments, including BC; thus, roles of circRNAs in this process have attracted significant attention. Methods: In this study, high-throughput sequencing was used for circRNA expression profiles analysis in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression regarding BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor the cell proliferation and invasion, respectively. We employed dual-luciferase reporter and RNA pulldown assays to verify the relationship among hsa_circ_0001944, miR-548, and PROK2. We examined the hsa_circ_0001944 effects on BC cell metastasis and proliferation in vivo through a subcutaneous xenograft model as well as an intravenous tail injection model of nude mice. Results: The result show that hsa_circ_0001944 expression increased significantly in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. Conclusions: Taken together, we found hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions like a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.


2020 ◽  
Author(s):  
Mingming Jin ◽  
Shengjie Lu ◽  
Yue Wu ◽  
Chen Yang ◽  
Chunzi Shi ◽  
...  

Abstract Background: Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in cancer development, including BC; thus, the roles of circRNAs in this process have attracted significant attention. Methods: In this study, high-throughput sequencing was used to analyze circRNA expression profiles in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression in BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor cell proliferation, invasion, and migration, respectively. We employed the dual-luciferase reporter and RNA pulldown assays to verify the relationships among hsa_circ_0001944, miR-548, and PROK2. We examined the effects of hsa_circ_0001944 on BC cell metastasis and proliferation in vivo using a subcutaneous xenograft model and an intravenous tail injection model in nude mice. Results: The results showed that hsa_circ_0001944 expression was significantly increased in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. Conclusions: Taken together, we found that hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions as a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xueyou Ma ◽  
Yufan Ying ◽  
Jiazhu Sun ◽  
Haiyun Xie ◽  
Jiangfeng Li ◽  
...  

AbstractCircular RNAs (circRNAs) play essential roles in human bladder cancer (BCa) development, however, unusual expression patterns and functional dysfunction of circRNAs in BCa have not been evaluated. In this study, we validated that circKDM4C (hsa_circ_0001839), derived from the KDM4C gene, is elevated in BCa cell lines as well as tissues. Functionally, overexpression of circKDM4C significantly enhances, and silencing of circKDM4C suppresses migration and invasion capabilities of BCa cells. Mechanistically, circKDM4C can directly interact with miR-200b-3p and miR-200c-3p as a miRNA sponge, which enhances the expression of ZEB1 and promotes mesenchymal phenotype. Conclusively, our findings indicate that circKDM4C may act as a pro-oncogenic factor in BCa invasion and metastasis via the circKDM4C/miR-200bc-3p/ZEB1 axis, which is a potential biomarker or therapeutic target for bladder cancer.


Author(s):  
Mingming Jin ◽  
Shengjie Lu ◽  
Yue Wu ◽  
Chen Yang ◽  
Chunzi Shi ◽  
...  

Abstract Background Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in cancer development, including BC; thus, the roles of circRNAs in this process have attracted significant attention. Methods In this study, high-throughput sequencing was used to analyze circRNA expression profiles in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression in BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor cell proliferation, invasion, and migration, respectively. We employed the dual-luciferase reporter and RNA pulldown assays to verify the relationships among hsa_circ_0001944, miR-548, and PROK2. We examined the effects of hsa_circ_0001944 on BC cell metastasis and proliferation in vivo using a subcutaneous xenograft model and an intravenous tail injection model in nude mice. Results The results showed that hsa_circ_0001944 expression was significantly increased in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. Conclusions Taken together, we found that hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions as a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoqi Yang ◽  
Tao Ye ◽  
Haoran Liu ◽  
Peng Lv ◽  
Chen Duan ◽  
...  

AbstractCircular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5′ caps and 3′ poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients’ survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.


2020 ◽  
Author(s):  
Mingming Jin ◽  
Shengjie Lu ◽  
Yue Wu ◽  
Chen Yang ◽  
Chunzi Shi ◽  
...  

Abstract Background: Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in cancer development, including BC; thus, the roles of circRNAs in this process have attracted significant attention. Methods: In this study, high-throughput sequencing was used to analyze circRNA expression profiles in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression in BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor cell proliferation, invasion, and migration, respectively. We employed the dual-luciferase reporter and RNA pulldown assays to verify the relationships among hsa_circ_0001944, miR-548, and PROK2. We examined the effects of hsa_circ_0001944 on BC cell metastasis and proliferation in vivo using a subcutaneous xenograft model and an intravenous tail injection model in nude mice. Results: The results showed that hsa_circ_0001944 expression was significantly increased in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. Conclusions: Taken together, we found that hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions as a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.


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