scholarly journals Circular RNA circFGFR1 Functions as an Oncogene in Glioblastoma Cells through Sponging to hsa-miR-224-5p

2022 ◽  
Vol 2022 ◽  
pp. 1-14
Author(s):  
Qian Zhang ◽  
Shan Chen ◽  
Yingwei Zhen ◽  
Peng Gao ◽  
Zhenyu Zhang ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Critical Role ◽  
Glioma Cells ◽  
Circular Rna ◽  
Cxcr4 Expression ◽  
Luciferase Reporter ◽  
Cxcr4 Mrna ◽  
Glioma Growth ◽  
Xenograft Models ◽  
New Perspective

Recently, increased studies have shown the important regulatory role of circular RNA (circRNA) in cancer progression and development, including glioblastoma (GBM). However, the function of circRNAs in glioblastoma is still largely unclear. Here, we state that circFGFR1 is elevated in glioma cells, resulting in aggravated glioma aggravated malignancy. The upregulation of circFGFR1 also promotes glioma growth in mouse xenograft models. Furthermore, CXCR4 level in glioma cells is positively correlated with circFGFR1 level, and higher CXCR4 expression is found in circFGFR1 overexpression groups. The effect of circFGFR1 on glioma malignancy is abolished in CXCR4 knockout cells. Then, RIP, RNA pull-down, and luciferase reporter assay results showed that hsa-miR-224-5p directly binds to circFGFR1 and CXCR4 mRNA. The CXCR4 3 ′ -untranslated region (UTR) activated luciferase activity was reduced with hsa-miR-224-5p transfection, while it is reversed when cotransfected with circFGFR1, indicating that circFGFR1 acts as a hsa-miR-244-5p sponge to increase CXCR4 expression. The hsa-miR-224-5p expression is negatively corrected with the glioma malignancy through inhibiting CXCR4 level. Besides, the circFGFR1-induced regulation in glioma malignancy is also abrogated in hsa-miR-224-5p knockout cells. Taken together, our findings suggest that circFGFR1 plays a critical role in the tumorigenic behaviors in glioma cells by upregulating CXCR4 expression via sponging to hsa-miR-224-5p. These findings provide a new perspective on circRNAs during GBM development.

scholarly journals The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Mingyi Zhou ◽  
Zhuo Yang ◽  
Danbo Wang ◽  
Peng Chen ◽  
Yong Zhang
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Critical Role ◽  
Circular Rna ◽  
Circular Rnas ◽  
Cyclin E1 ◽  
Normal Tissues ◽  
Exact Function ◽  
Potential Biomarker

Abstract Background As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR. Results Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.

Circular RNA hsa_circ_0078607 suppresses ovarian cancer progression by regulating miR-518a-5p/Fas signaling pathway

2020 ◽  
Author(s):  
Nan Zhang ◽  
Yue Jin ◽  
Qiubo Hu ◽  
Shanshan Cheng ◽  
Chao Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Malignant Tumors ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Cancer Pathogenesis ◽  
Direct Target

Abstract Background: Increasing researches have demonstrated the critical functions of circular RNAs (circRNAs) in the progression of malignant tumors, including ovarian cancer. In this study, we aim to investigate abnormally expression of hsa_circ_0078607 and the role of hsa_circ_0078607 during ovarian cancer pathogenesis.Methods: RT-PCR were used to detect the expression of circ_0078607 in ovarian cancer tissues. To determine the functional roles of circ_0078607 in ovarian cancer, cell proliferation and cell invasion assays were performed. Bioinformatics and luciferase reporter analysis were used to predict the target of circ_0078607.Results: In the present study, we first found that circ_0078607 was downregulated in ovarian cancer. Forced circ_0078607 expression significantly suppressed proliferation and promotes apoptosis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified that miR-518a-5p as a direct target of circ_0078607, while Fas as a direct target of miR-518a-5p. MiR-518a-5p negatively regulates Fas in ovarian cancer cells, while overexpression of circ_0078607 could increase the expression of Fas inhibited by miR-518a-5p. Furthermore, overexpression of circ_0078607 could inhibit the proliferation and invasion of ovarian cancer cells caused by miR-518a-5p mimic.Conclusion: The results of the present study revealed that circ_0078607 suppresses ovarian cancer progression by sponging oncogenic miR-518a-5p to induce Fas expression, which may provide new therapeutic approach for ovarian cancer.

scholarly journals Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qun Dai ◽  
Jingyi Deng ◽  
Jinrong Zhou ◽  
Zhuhong Wang ◽  
Xiao-feng Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Marked Rise ◽  
Hcc Cells

Abstract Background Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. Methods The expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo. Results We found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2. Conclusion TUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.

scholarly journals Circular RNA circFAT1(e2) Promotes Osteosarcoma Progression and Metastasis by Sponging miR-181b and Regulating HK2 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Huijie Gu ◽  
Xiangyang Cheng ◽  
Jun Xu ◽  
Kaifeng Zhou ◽  
Chong Bian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Therapeutic Target ◽  
Critical Role ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Expression Level ◽  
Circular Rnas ◽  
Competing Endogenous Rna ◽  
Potential Therapeutic Target

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR-181b, while miR-181b targeted HK2. By releasing the inhibition of miR-181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR-181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR-181b/HK2 axis might be a potential therapeutic target.

scholarly journals The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex

2021 ◽  
Author(s):  
Mingyi Zhou ◽  
Zhuo Yang ◽  
Danbo Wang ◽  
Peng Chen ◽  
Yong Zhang
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Critical Role ◽  
Circular Rna ◽  
Circular Rnas ◽  
Cyclin E1 ◽  
Normal Tissues ◽  
Exact Function ◽  
Potential Biomarker

Abstract Background: As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods: We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change >2, and P <0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.Results: Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion: Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.

scholarly journals The Circ_0001367/miR-545-3p/LUZP1 Axis Regulates Cell Proliferation, Migration and Invasion in Glioma Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuchen Dong ◽  
Peng Zhang ◽  
Liang Liu ◽  
Haoran Li ◽  
Shan Cheng ◽  
...  
Keyword(s):  
Leucine Zipper ◽  
Cell Function ◽  
Glioma Cells ◽  
Malignant Tumour ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function

Glioma is the most common primary intracranial malignant tumour in adults. It has a high incidence and poses a serious threat to human health. Circular RNA is a hotspot of cancer research. In this study, we aimed to explore the role of circ_0001367 in gliomagenesis and the underlying mechanism. First, qRT-PCR was conducted, which showed that circ_0001367 level was downregulated in glioma tissues and cells. Next, gain-of-function and loss-of-function assays were performed, which indicated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells. Subsequent bioinformatics analysis, dual-luciferase reporter assays, RNA immunoprecipitation assays and cell function assays demonstrated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells by absorbing miR-545-3p and thereby regulating the expression of leucine zipper protein (LUZP1). Finally, an in vivo experiment was conducted, which demonstrated that circ_0001367 inhibited glioma growth in vivo by modulating miR-545-3p and LUZP1. Taken together, the results of this study demonstrate that the circ_0001367/miR-545-3p/LUZP1 axis may be a novel target for glioma therapy.

scholarly journals The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex

2021 ◽  
Author(s):  
Mingyi Zhou ◽  
Zhuo Yang ◽  
Danbo Wang ◽  
Peng Chen ◽  
Yong Zhang
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Critical Role ◽  
Circular Rna ◽  
Circular Rnas ◽  
Cyclin E1 ◽  
Normal Tissues ◽  
Exact Function ◽  
Potential Biomarker

Abstract Background: As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods: We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change >2, and P <0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.Results: Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion: Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.

scholarly journals Circular RNA circANKS1B as the Sponge of miR-152-3p Promotes Prostate Cancer Progression by up-Regulating TGF-α Expression

2020 ◽  
Author(s):  
Liangjun Tao ◽  
Xinyuan Pan ◽  
Jiawei Wang ◽  
Li Zhang ◽  
Lingsong Tao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Prostate Cancer Progression ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
And Function ◽  
The Impact

Abstract Background: Growing studies indicate that circRNAs play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aims to investigate the expression and function of circANKS1B in prostate cancer (PC).Methods: The expression of circANKS1B and miRNA-152-3p were determined by real-time qRT-PCR. The cell migration and invasion were measured by transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by dual-luciferase reporter gene assay. Rescue experiments were conducted to demonstrate whether circANKS1B regulated the migration and invasion of PC cells by the circANKS1B-miR-152-3p-TGF-α pathway.Results: The expression of circANKS1B was dramatically up-regulated both in PC cells and tissues. Moreover, high circANKS1B expression was associated with a poor prognosis of PC patients. Dual-luciferase reporter assay indicated that circABKS1B directly bound to miRNA-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B remarkably suppressed PC cells invasion and TGF-α expression, while the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on PC cell invasion was also abrogated by TGF-α deficiency. In all, circANKS1B as the sponge of miR-152-3p promotes prostate cancer progression by up-regulating TGF-α expression.Conclusion: Our findings reveal that circANKS1B could be a potential prognostic biomarker and therapeutic target of PC.

scholarly journals Circ_0078607 inhibits the progression of ovarian cancer via regulating the miR-32-5p/SIK1 network

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Yangqiu Jin ◽  
Hui Wang
Keyword(s):  
Ovarian Cancer ◽  
Circular Rna ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
In Vivo Experiments ◽  
Xenograft Models ◽  
Apoptosis Marker

Abstract Background Circular RNA (circRNA) has been shown to be involved in the regulation of human disease progression, including ovarian cancer (OC). Circ_0078607 was found to participate in OC progression. But its function and mechanism in OC deserve further exploration. Methods The expression levels of circ_0078607, salt-inducible kinase 1 (SIK1) and microRNA (miR)-32-5p were examined by qRT-PCR. And the protein expression levels of SIK1, metastasis marker and apoptosis marker were determined using western blot analysis. EDU staining, colony formation assay, transwell assay and flow cytometry were used to detect the proliferation, migration, invasion and apoptosis of cells. Moreover, dual-luciferase reporter assay was employed to verify the interaction between miR-32-5p and circ_0078607 or SIK1. Xenograft models were constructed to perform in vivo experiments. Results Circ_0078607 and SIK1 were downregulated in OC tissues and cells. Overexpressed circ_0078607 and SIK1 could inhibit OC cell proliferation, migration, invasion, and promote apoptosis. MiR-32-5p could be sponged by circ_0078607, and its overexpression could reverse the suppressive effect of circ_0078607 on OC progression. Furthermore, SIK1 was a target of miR-32-5p, and circ_0078607 could regulate SIK1 by sponging miR-32-5p. The inhibitory effect of circ_0078607 on OC progression also could be reversed by SIK1 silencing. In vivo experiments showed that circ_0078607 reduced OC tumorigenesis by regulating the miR-32-5p/SIK1 axis. Conclusion Circ_0078607 could serve as a sponge of miR-32-5p to regulate SIK1 expression, thereby inhibiting OC progression.

Circular RNA HIPK3 plays a carcinogenic role in cervical cancer progression via regulating miR-485-3p/FGF2 axis

2020 ◽  
pp. jim-2020-001537
Author(s):  
Shanshan Wu ◽  
Shimei Liu ◽  
Huaihua Song ◽  
Jiayu Xia
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pcr Assay ◽  
Fgf2 Expression ◽  
Proliferation And Metastasis ◽  
Dual Luciferase Reporter Assay

Circular RNA (circRNA) is an endogenous RNA molecule with a stable closed-loop structure. The circular RNA HIPK3 (circHIPK3) is highly expressed in hepatocellular carcinoma and facilitates tumor growth. However, its role in cervical cancer (CC) and its regulatory mechanisms are not well-studied. This study aimed for investigating the function of circHIPK3 on proliferation and metastasis of CC cells. In this study, quantitative real-time PCR assay was adopted to delve into the circHIPK3 expression in CC cell lines. Cell counting kit-8 and colony formation assays were used to evaluate the influence of overexpression and knockdown of circHIPK3 on CC cell proliferation. Dual-luciferase reporter assay was employed to probe into the binding of miR-485-3p to circHIPK3 and miR-485-3p to the 3’ untranslated region (UTR) of fibroblast growth factor 2 (FGF2), respectively. FGF2 protein expression was detected by western blot analysis. This study confirmed that circHIPK3 was highly expressed in CC tissues. Overexpressed circHIPK3 could remarkably expedite the proliferation, migration and invasion of SiHa cells, and knocking down circHIPK3 could significantly impede the proliferation, migration and invasion of HeLa cells. MiR-485-3p can directly bind to circHIPK3 and the 3’UTR of FGF2. Overexpression of circHIPK3 triggered the upregulation of FGF2 expression while knockdown of circHIPK3 reduced FGF2 expression in CC cells, and the transfection of miR-485-3p mimics reversed the upregulation of FGF2 expression and enhanced malignant phenotypes in CC cells with overexpressed circHIPK3.

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