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

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.

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

10.21203/rs.3.rs-45694/v3 ◽

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.

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The Circular RNA circZFR Phosphorylates Rb Promoting Cervical Cancer Progression by Regulating the SSBP1/CDK2/cyclin E1 Complex

10.21203/rs.3.rs-45694/v1 ◽

2020 ◽

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.

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

10.21203/rs.3.rs-45694/v2 ◽

2020 ◽

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.

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

BioMed Research International ◽

10.1155/2020/3589871 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7 ◽

Cited By ~ 1

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.

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CircAGFG1 promotes cervical cancer progression via miR-370-3p/RAF1 signaling

BMC Cancer ◽

10.1186/s12885-019-6269-x ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Fengqin Wu ◽

Jingjing Zhou

Keyword(s):

Cervical Cancer ◽

Cancer Progression ◽

Circular Rnas ◽

Great Promise ◽

Erk Pathway ◽

Loss Of Function ◽

Potential Biomarker ◽

And Migration ◽

Proliferation And Migration

Abstract Background In past decades, circular RNAs (circRNAs) have achieved increasing attention because of its regulatory role in different kinds of cancers. However, how circAGFG1 regulates cervical cancer (CC) is still largely undiscovered. This study aims to evaluate the role of a novel circRNAs and related molecular mechanism in CC cells. Methods High or low level of circAGFG1 was detected in CC cells or normal cell line with qRT-PCR. The proliferative and migratory abilities of CC cells were assessed with loss-of function assays. The downstream miRNA and mRNA of circAGFG1 were searched out and proved by using bioinformatics analysis and mechanism experiments. Recue assays were designed to confirm the role of circAGFG1/miR-370-3p/RAF1 axis in CC cell activities. Results The levels of circAGFG1 was abundant in CC cells in comparison with normal cervical cell End1/E6E7. The inhibitory effect of decreased circAGFG1 level on the proliferative and migratory abilities of CC cells was assessed. CircAGFG1 and miR-370-3p were localized in the cytoplasm and they can interact with each other. Moreover, miR-370-3p was downregulated in CC cells. We also determined the negative effect of miR-370-3p on RAF1. CircAGFG1 could promote RAF1 expression by absorbing miR-370-3p, thereby activating RAF/MEK/ERK pathway. circAGFG1 promoted proliferation and migration of CC cells via enhancing the activity of RAF/MEK/ERK pathway by sponging miR-370-3p and further regulating RAF1. Conclusion The results of this study provided new evidence that circAGFG1 acted as a vital regulator in cervical cancer proliferation and migration, giving great promise to apply it as a potential biomarker for diagnosis and therapy in CC treatment.

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Circular RNA circYPEL2: A Novel Biomarker in Cervical Cancer

Genes ◽

10.3390/genes13010038 ◽

2021 ◽

Vol 13 (1) ◽

pp. 38

Author(s):

Xinyang Zhang ◽

Siqi Yang ◽

Wenbo Chen ◽

Xin Dong ◽

Rongyu Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Lines ◽

High Throughput ◽

High Throughput Sequencing ◽

Strong Stability ◽

Circular Rna ◽

Migration And Invasion ◽

Circular Rnas ◽

Cancer Hallmarks ◽

Potential Biomarker

Cervical cancer (CC) is one of the most threatening diseases in women. Circular RNAs (circRNAs) have been reported to be cancer hallmarks, but typical circRNAs in CC were rarely indicated. Through high-throughput sequencing in CC and normal cervix tissues, circYPEL2 (hsa_circ_0005600) was proposed as a candidate circRNA. CircYPEL2 exhibited significantly high expression in CC tissue and strong stability in CC cell lines. Furthermore, knockdown and overexpression of circYPEL2 indicated the potential involvement in CC proliferation, migration and invasion. Finally, the downstream regulatory genes of circYPEL2 were investigated by knockdown experiment in CC cell lines with high-throughput sequencing. In summary, our work identified circYPEL2 as a potential biomarker for clinical research of cervical cancer.

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Circular RNA ZNF609 functions as a competing endogenous RNA in regulating E2F transcription factor 6 through competitively binding to microRNA-197-3p to promote the progression of cervical cancer progression

Bioengineered ◽

10.1080/21655979.2021.1896116 ◽

2021 ◽

Vol 12 (1) ◽

pp. 927-936

Author(s):

Qiao Gu ◽

Wenjie Hou ◽

Lijuan Shi ◽

Huan Liu ◽

Zonghao Zhu ◽

...

Keyword(s):

Cervical Cancer ◽

Transcription Factor ◽

Cancer Progression ◽

Circular Rna ◽

Competing Endogenous Rna ◽

E2f Transcription Factor

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Oncogenic role of ALX3 in cervical cancer cells through KDM2B-mediated histone demethylation of CDC25A

BMC Cancer ◽

10.1186/s12885-021-08552-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jinhong Qi ◽

Li Zhou ◽

Dongqing Li ◽

Jingyuan Yang ◽

He Wang ◽

...

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Cell Cycle Progression ◽

Cervical Squamous Cell Carcinoma ◽

Cycle Progression ◽

Normal Tissues ◽

Positive Regulator ◽

Cervical Cancer Cells

Abstract Background Cell division cycle 25A (CDC25A) is a well-recognized regulator of cell cycle progression and is involved in cancer development. This work focused on the function of CDC25A in cervical cancer cell growth and the molecules involved. Methods A GEO dataset GSE63514 comprising data of cervical squamous cell carcinoma (CSCC) tissues was used to screen the aberrantly expressed genes in cervical cancer. The CDC25A expression in cancer and normal tissues was predicted in the GEPIA database and that in CSCC and normal cells was determined by RT-qPCR and western blot assays. Downregulation of CDC25A was introduced in CSCC cells to explore its function in cell growth and the cell cycle progression. The potential regulators of CDC25A activity and the possible involved signaling were explored. Results CDC25A was predicted to be overexpressed in CSCC, and high expression of CDC25A was observed in CSCC cells. Downregulation of CDC25A in ME180 and C33A cells reduced cell proliferation and blocked cell cycle progression, and it increased cell apoptosis. ALX3 was a positive regulator of CDC25A through transcription promotion. It recruited a histone demethylase, lysine demethylase 2B (KDM2B), to the CDC25A promoter, which enhanced CDC25A expression through demethylation of H3k4me3. Overexpression of ALX3 in cells blocked the inhibitory effects of CDC25A silencing. CDC25A was found as a positive regulator of the PI3K/Akt signaling pathway. Conclusion This study suggested that the ALX3 increased CDC25A expression through KDM2B-mediated demethylation of H3K4me3, which induced proliferation and cell cycle progression of cervical cancer cells.

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Circular RNA hsa_circ_0043280 inhibits cervical cancer tumor growth and metastasis via miR-203a-3p/PAQR3 axis

Cell Death and Disease ◽

10.1038/s41419-021-04193-7 ◽

2021 ◽

Vol 12 (10) ◽

Author(s):

Chunyu Zhang ◽

Pan Liu ◽

Jiaming Huang ◽

Yuandong Liao ◽

Chaoyun Pan ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Poor Prognosis ◽

Prognostic Biomarker ◽

Circular Rna ◽

Circular Rnas ◽

Inhibit Tumor Growth ◽

Cancer Tumor ◽

Tumor Growth And Metastasis

AbstractCircular RNAs (circRNAs) are known to act as key regulators in a variety of malignancies. However, the role of circRNAs in cervical cancer (CCa) remains largely unknown. Herein, we demonstrated that a circRNA derived from the TADA2A gene (hsa_circ_0043280) was significantly downregulated in CCa and that this reduction in expression was correlated with a poor prognosis. Furthermore, our results demonstrated that hsa_circ_0043280 functions as a tumor suppressor to inhibit tumor growth and metastasis in CCa. Mechanistically, hsa_circ_0043280 competitively sponges miR-203a-3p and prevents miR-203a-3p from reducing the levels of PAQR3. Collectively, our results demonstrate that hsa_circ_0043280 plays a pivotal role in the development and metastasis of CCa, thus suggesting that hsa_circ_0043280 has significant potential as a prognostic biomarker and a therapeutic target for CCa.

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