scholarly journals CircRNA_0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis

2019 ◽  
Author(s):  
Haote Liang ◽  
Hang Huang ◽  
Yeping Li ◽  
Yongyong Lu ◽  
Tingyu Ye
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Tumorigenesis And Progression ◽  
Rna Immunoprecipitation ◽  
Reporter Assays ◽  
Proliferation And Invasion

Abstract Emerging evidences have uncovered critical regulatory roles of circular RNAs (circRNAs) function as dynamic scaffolding molecules in tumorigenesis and progression. However, the aberrant expression and clinical significance of hsa_circ_0058063 (circRNA_0058063) in bladder cancer (BC) remain poorly understood. circRNA expression was analyzed via a microarray in cancerous tissue and non-carcinoma tissues. Luciferase reporter assays and RNA immunoprecipitation (RIP) were both conducted to uncover the function of circRNA_0058063 in BC. circRNA_0058063 was overexpressed in BC tissues compared to adjacent normal tissues. Knockdown of circRNA_0058063 dramatically decreased cell proliferation and invasion, and promoted apoptosis in 5637 and BIU-87 cell lines. Furthermore, mechanistic investigations showed that circRNA_0058063 and FOXP4 could directly bind to miR-486-3p, demonstrating that circRNA_0058063 regulated FOXP4 expression by competitively binding to miR-486-3p. Taken together, circRNA_0058063 functions by sponging miR-486-3p in BC progression, which could be act as a new biomarker and further developed to be a therapeutic target in BC.

scholarly journals CircRNA 0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis

2019 ◽  
Author(s):  
Haote Liang ◽  
Hang Huang ◽  
Yeping Li ◽  
Yongyong Lu ◽  
Tingyu Ye
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Tumorigenesis And Progression ◽  
Rna Immunoprecipitation ◽  
Reporter Assays ◽  
Proliferation And Invasion

Abstract Emerging evidences have uncovered critical regulatory roles of circular RNAs (circRNAs) function as dynamic scaffolding molecules in tumorigenesis and progression. However, the aberrant expression and clinical significance of hsa_circ_0058063 (circRNA_0058063) in bladder cancer (BC) remain poorly understood. circRNA expression was analyzed via a microarray in cancerous tissue and non-carcinoma tissues. Luciferase reporter assays and RNA immunoprecipitation (RIP) were both conducted to uncover the function of circRNA_0058063 in BC. circRNA_0058063 was overexpressed in BC tissues compared to adjacent normal tissues. Knockdown of circRNA_0058063 dramatically decreased cell proliferation and invasion, and promoted apoptosis in 5637 and BIU-87 cell lines. Furthermore, mechanistic investigations showed that circRNA_0058063 and FOXP4 could directly bind to miR-486-3p, demonstrating that circRNA_0058063 regulated FOXP4 expression by competitively binding to miR-486-3p. Taken together, circRNA_0058063 functions by sponging miR-486-3p in BC progression, which could be act as a new biomarker and further developed to be a therapeutic target in BC.

scholarly journals CircRNA_0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Haote Liang ◽  
Hang Huang ◽  
Yeping Li ◽  
Yongyong Lu ◽  
Tingyu Ye
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Tumorigenesis And Progression ◽  
Rna Immunoprecipitation ◽  
Reporter Assays ◽  
Proliferation And Invasion

Abstract Emerging evidence has uncovered critical regulatory roles of circular RNAs (circRNAs) function as dynamic scaffolding molecules in tumorigenesis and progression. However, the aberrant expression and clinical significance of hsa_circ_0058063 (circRNA_0058063) in bladder cancer (BC) remain poorly understood. circRNA expression was analyzed via a microarray in cancerous tissue and non-carcinoma tissues. Luciferase reporter assays and RNA immunoprecipitation (RIP) were both conducted to uncover the function of circRNA_0058063 in BC. circRNA_0058063 was overexpressed in BC tissues compared with adjacent normal tissues. Knockdown of circRNA_0058063 dramatically decreased cell proliferation and invasion, and promoted apoptosis in 5637 and BIU-87 cell lines. Furthermore, mechanistic investigations showed that circRNA_0058063 and FOXP4 could directly bind to miR-486-3p, demonstrating that circRNA_0058063 regulated FOXP4 expression by competitively binding to miR-486-3p. Taken together, circRNA_0058063 functions by sponging miR-486-3p in BC progression, which could act as a new biomarker and further developed to be a therapeutic target in BC.

scholarly journals Hsa_circ_0004370 promotes esophageal cancer progression through miR-1294/LASP1 pathway

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhenyang Zhang ◽  
Wenwei Lin ◽  
Lei Gao ◽  
Keqing Chen ◽  
Chuangcai Yang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Multiple Roles ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Rescue Effect ◽  
Rna Immunoprecipitation ◽  
Si Rna ◽  
Proliferation And Invasion

AbstractCircular RNAs (circRNAs) formed by back-splicing play multiple roles in the occurrence and development of cancer. Here, we found that hsa_circ_0004370 was up-regulated in both esophageal cancer (EC) tissues and cell lines. Loss function of hsa_circ_0004370 by si-RNA significantly suppressed proliferation and invasion and promoted apoptosis in both EC cell lines. The sponging of miR-1294 by hsa_circ_0004370 was bioinformatically predicted and subsequently verified by luciferase reporter assay and RNA immunoprecipitation assay. Further, hsa_circ_0004370 involved in the up-regulation of LASP1 by sponging miR-1294. Besides, the inhibition of the down-regulated hsa_circ_0004370 on cell malignant behaviors was rescued by miR-1294 inhibitor. Finally, this rescue effect was abrogated by suppressing the expression of LASP1. The results present here suggest that hsa_circ_0004370 functions as an oncogene on cell proliferation, apoptosis, and invasion via miR-1294/LASP1 axis.

scholarly journals CircZNF609 Promotes Bladder Cancer Progression and Inhibits Cisplatin Sensitivity via miR-1200/CDC25B Pathway

2021 ◽  
Author(s):  
Dexiang Feng ◽  
Jiancheng Lv ◽  
Kai Li ◽  
Qiang Cao ◽  
Jie Han ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Tumor Development ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Online Databases ◽  
Cisplatin Sensitivity ◽  
Cisplatin Chemoresistance

Abstract Circular RNAs (circRNAs) have been extensively studied in tumor development and treatment. CircZNF609 has been shown to act as an oncogene in a variety of solid tumors and may serve as a novel biomarker for tumor diagnosis and treatment. However, the underlying role and mechanism of circZNF609 in bladder cancer (BCa) development and cisplatin chemosensitivity were unknown. Quantitative real-time PCR (qRT-PCR) was applied to determine the expression of circZNF609, microRNA 1200 (miR-1200) and CDC25B in BCa cells and tissues. Western blot was used to detect the protein level of CDC25B. Functional assays in vitro and in vivo were conducted to investigate the effects of circZNF609 on tumor development and cisplatin chemosensitivity in BCa. RNA sequencing and online databases were used to predict the interactions among circZNF609, miR-1200 and CDC25B. Dual luciferase reporter assay, RNA pull-down assay and RNA fluorescence in situ hybridization (FISH) were applied to confirm the mechanism. CircZNF609 expression was significantly up-regulated in BCa cell lines and tissues. Increased expression of circZNF609 was related to a worse survival in BCa patients. In vitro and in vivo, enforced-expression of circZNF609 enhanced BCa cells proliferation, migration and cisplatin chemoresistance. Mechanistically, circZNF609 alleviated the inhibition effect on target CDC25B expression by sponging miR-1200. CircZNF609 promoted tumor growth through novel circZNF609/miR-1200/CDC25B axis, implying that circZNF609 has significant potential to serve as a new diagnostic biomarker and therapeutic target for BCa patients.

Aberrant expression of hsa_circ_0025036 in lung adenocarcinoma and its potential roles in regulating cell proliferation and apoptosis

2018 ◽  
Vol 399 (12) ◽  
pp. 1457-1467 ◽  
Author(s):  
Shujun Wu ◽  
Hui Li ◽  
Chunya Lu ◽  
Furui Zhang ◽  
Huaqi Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Luciferase Reporter ◽  
Clinicopathological Parameters ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Close Link ◽  
Adenocarcinoma Cells ◽  
Proliferation And Apoptosis ◽  
Reporter Assays

AbstractAs the most common histological subtype of lung cancer, lung adenocarcinoma remains a tremendous risk to public health, which requires ceaseless efforts to elucidate the potential diagnostic and therapeutic strategies. Circular RNAs (circRNAs) have been identified with emerging roles in tumorigenesis and development. Our preliminary work noticed that hsa_circ_0025036 was significantly upregulated in lung adenocarcinoma tissues. However, its specific roles in lung adenocarcinoma remain unclear. The results in this study revealed that hsa_circ_0025036 existed as a circular form and was aberrantly upregulated in lung adenocarcinoma tissues via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Its expression level exhibited a close link with aggressive clinicopathological parameters including cancer differentiation, TNM stage and lymph node metastasis. hsa_circ_0025036 knockdown significantly suppressed cell proliferation and promoted cell apoptosis in A549 and Calu-3 cells. Moreover, hsa_circ_0025036/miR-198/SHMT1&TGF-αaxis was identified via bioinformatics analysis and Dual-Luciferase Reporter assays. miR-198 inhibitors reversed the function of hsa_circ_0025036 knockdown. hsa_circ_0025036 knockdown exerted similar effects with miR-198 upregulation on cell proliferation and apoptosis. In conclusion, we demonstrate that hsa_circ_0025036 regulates cell proliferation and apoptosis in lung adenocarcinoma cells probably via hsa_circ_0025036/miR-198/SHMT1&TGF-αaxis. hsa_circ_0025036 may serve as a potential prognostic biomarker and a therapeutic target for lung adenocarcinoma.

scholarly journals miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 224-236
Author(s):  
Lijuan Ke ◽  
Yanping Chen ◽  
Yiying Li ◽  
Zheng Chen ◽  
Yihui He ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Hela Cells ◽  
Luciferase Reporter ◽  
Carcinogenic Effect ◽  
Expression Levels ◽  
Normal Tissues ◽  
Homeobox Transcription Factor ◽  
Reporter Assays ◽  
Cancer Tissues

Abstract Background Previous work has shown that miR-142-5p in cervical cancer tissues increased significantly compared with adjacent normal tissues. However, the function and the mechanism of miR-142-5p in cervical cancer have not been reported. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the gene expression levels. MTT, flow cytometry, and transwell assays were performed to explore the functions of miR-142-5p in HeLa cells. The potential target gene of miR-142-5p was investigated via luciferase reporter assays. The protein expression levels were analyzed by Western blotting. Results We found that miR-142-5p expression was elevated but LIM homeobox transcription factor 1 alpha (LMX1A) was decreased in cervical cancer tissues and cells. Overexpression of miR-142-5p or knockdown of LMX1A inhibited cell apoptosis, promoted cell proliferation, migration, invasion abilities, and activated the Wnt/β-catenin pathway. However, knockdown of miR-142-5p or overexpression of LMX1A showed opposite results. LMX1A was identified as a direct target of miR-142-5p by luciferase reporter assays. Finally, rescue experiments demonstrated that LMX1A overexpression attenuated the carcinogenic effect of miR-142-5p mimic on HeLa cells. Conclusions These findings suggested that miR-142-5p might be a cervical cancer oncogene and could serve as a potential therapeutic target for the treatment of cervical cancer.

scholarly journals ELK4-mediated lncRNA SNHG22 promotes gastric cancer progression through interacting with EZH2 and regulating miR-200c-3p/Notch1 axis

2021 ◽  
Author(s):  
Xiaqiong Mao ◽  
Tao Ji ◽  
Aiguo Liu ◽  
Yunqi Weng
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Tumor Suppressor Genes ◽  
Luciferase Reporter ◽  
Diagnosis And Prognosis ◽  
Reporter Assays ◽  
Non Coding Rnas ◽  
Gastric Cancer Progression ◽  
Proliferation And Invasion

Abstract Background Long non-coding RNAs (lncRNAs) play important regulatory roles in the initiation and progression of various cancers. However, the biological roles and the potential mechanisms of lncRNAs in gastric cancers remain unclear. Methods The expression of SNHG22 in gastric cancer was analyzed in public databases (TCGA) and validated via qRT-PCR. SNHG22 knockdown cell lines were construced, and cell proliferation and invasion were analyzed. CHIP and luciferase reporter assays were performed to clarify the transcriptional role of ELK4. RNA pull-down followed MS and RIP assays were employed to identify the interaction between SNHG22 and EZH2. Luciferase reporter assays and RIP assays were used to confirm the regulation of SNHG22 on Notch1 by sponging miR-2003-3p. Results Knockdown of SNHG22 inhibited the proliferation and invasion ability of GC cells. Moreover, we identified that the transcriptional factor, ELK4, could promote SNHG22 expression in GC cells. In addition, using RNA pull-down followed MS assay, we found that SNHG22 directly bound to EZH2 to suppress the expression of tumor suppressor genes. At the same time, SNHG22 sponged miR-200c-3p to increase Notch1 expression. Conclusions Taken together, our findings demonstrated the role of SNHG22 on promoting proliferation and invasion of GC cells. And we revealed a new regulatory mechanism of SNHG22 in GC cells. SNHG22 is a promising lncRNA biomarker for diagnosis and prognosis and a potential target for GC treatment.

scholarly journals circRIP2 accelerates bladder cancer progression via miR-1305/Tgf-β2/smad3 pathway

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Yinjie Su ◽  
Weilian Feng ◽  
Juanyi Shi ◽  
Luping Chen ◽  
Jian Huang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Rna Sequencing ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Sequencing Analysis ◽  
Potential Biomarker

Abstract Background Increasing evidences indicate that circular RNAs exert critical function in regulating bladder cancer progression. However, the expressive patterns and roles of circular RNAs in bladder cancer remain less investigated. Methods circRIP2 was identified and evaluated by RNA-sequencing and qPCR; in vitro effects of circRIP2 were determined by CCK8, clone forming, wound healing and trans-well assays; while mice subcutaneous tumor model was designed for in vivo analysis. Western blot, RNA pulldown assay, miRNA capture and dual luciferase assessment were applied for mechanistic studies. Results circRIP2 was identified as a conserved and dramatically repressed circular RNA in bladder cancer. Patients that displayed higher circRIP2 expression negatively associate with the grade, stage, metastasis as well as outcome of bladder cancer. In vitro and in vivo studies suggest that circRIP2 enables to promote bladder cancer progression via inducing EMT. Regarding the mechanism, we performed RNA-sequencing analysis, RNA pulldown with biotin-labeled circRIP2-specific probe, dual luciferase reporter assay. It was found that circRIP2 enables to sponge miR-1305 to elevate Tgf-β2 in bladder cancer, and inducing EMT via Tgf-β2/smad3 pathway. Blocking Tgf-β2 in bladder cancer deprives circRIP2 induced cancer progression and EMT. Conclusions Taken together, our study provides the first evidence that circRIP2 expresses differentially in bladder cancer and negatively along with the cancer progression; effective circRIP2 activity accelerates bladder cancer progression via inducing EMT by activating miR-1305/Tgf-β2/smad3 pathway. The research implies that circRIP2 might be a potential biomarker and therapeutic target for bladder cancer patients.

scholarly journals CircPTPRA blocks the recognition of RNA N6-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fei Xie ◽  
Chao Huang ◽  
Feng Liu ◽  
Hui Zhang ◽  
Xingyuan Xiao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Clinical Role ◽  
Rna Immunoprecipitation

Abstract Background Circular RNAs (circRNAs) have been found to have significant impacts on bladder cancer (BC) progression through various mechanisms. In this study, we aimed to identify novel circRNAs that regulate the function of IGF2BP1, a key m6A reader, and explore the regulatory mechanisms and clinical significances in BC. Methods Firstly, the clinical role of IGF2BP1 in BC was studied. Then, RNA immunoprecipitation sequencing (RIP-seq) analysis was performed to identify the circRNAs interacted with IGF2BP1 in BC cells. The overall biological roles of IGF2BP1 and the candidate circPTPRA were investigated in both BC cell lines and animal xenograft studies. Subsequently, we evaluated the regulation effects of circPTPRA on IGF2BP1 and screened out its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circPTPRA might act as a blocker in recognition of m6A. Results We demonstrated that IGF2BP1 was predominantly binded with circPTPRA in the cytoplasm in BC cells. Ectopic expression of circPTPRA abolished the promotion of cell proliferation, migration and invasion of BC cells induced by IGF2BP1. Importantly, circPTPRA downregulated IGF2BP1-regulation of MYC and FSCN1 expression via interacting with IGF2BP1. Moreover, the recognition of m6A-modified RNAs mediated by IGF2BP1 was partly disturbed by circPTPRA through its interaction with KH domains of IGF2BP1. Conclusions This study identifies exonic circular circPTPRA as a new tumor suppressor that inhibits cancer progression through endogenous blocking the recognition of IGF2BP1 to m6A-modified RNAs, indicating that circPTPRA may serve as an exploitable therapeutic target for patients with BC.

scholarly journals Circular RNA circ-ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/p21 axis and acts as a prognostic factor of recurrence

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Junming Bi ◽  
Hongwei Liu ◽  
Wei Dong ◽  
Weibin Xie ◽  
Qingqing He ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Progression ◽  
Tumor Grade ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Rank Test ◽  
Circular Rnas

Abstract Background Circular RNAs (circRNAs) represent a subclass of regulatory RNAs that have been shown to have significant regulatory roles in cancer progression. However, the biological functions of circRNAs in bladder cancer (BCa) are largely unknown. Methods Cell invasion models were established, and invasion-related circRNAs were detected by qPCR. Using above method, circ-ZKSCAN1 was picked out for further study. Circ-ZKSCAN1 expression and survival analyses were performed through qPCR. The survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to assess the significance. Cell proliferation, migration and invasion were examined to investigate the function of circ-ZKSCAN1. Tumorigenesis in nude mice was assessed to determine the effect of circ-ZKSCAN1 in bladder cancer. Biotin-coupled probe pull-down assays, FISH and luciferase reporter assays were conducted to confirm the relationship between circ-ZKSCAN1 and microRNA. RNA-seq revealed different molecular changes in downstream genes. Results Here, we found that circ-ZKSCAN1 was downregulated in BCa tissues and cell lines. Circ-ZKSCAN1 levels were associated with survival, tumor grade, pathological T stage and tumor recurrence. Overexpressed circ-ZKSCAN1 inhibits cell proliferation, migration, invasion and metastasis in vitro and in vivo. Mechanistically, we demonstrated that circ-ZKSCAN1 upregulated p21 expression by sponging miR-1178-3p, which suppressed the aggressive biological behaviors in bladder cancer. Conclusions These results reveal that Circ-ZKSCAN1 acts as a tumor suppressor via a novel circ-ZKSCAN1/miR-1178-3p/p21 axis, which have the important role in the proliferation, migration and invasion ablitities of BCa cells and provide a novel perspective on circRNAs in BCa progression.

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