scholarly journals Hsa_circ_0107593 Suppresses the Progression of Cervical Cancer via Sponging hsa-miR-20a-5p/93-5p/106b-5p

2021 ◽  
Vol 10 ◽  
Author(s):  
Wenyan Liao ◽  
Jun He ◽  
Cyrollah Disoma ◽  
Yi Hu ◽  
Junhua Li ◽  
...  

Circular RNAs (circRNAs) are a new class of single-stranded RNAs that form a continuous loop with crucial role in regulation of gene expression. Because their circular conformation conforms numerous properties, circRNAs have been investigated recently to demonstrate their important role in the development and progression of various cancers. However, the function of circRNAs and their regulatory outcomes in cervical cancer (CC) have rarely been explored. In this study, the role and molecular mechanism of hsa_circ_0107593 in cervical cancer are demonstrated. Quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of hsa_circ_0107593 and three miRNAs (hsa-miR-20a-5p, 93-5p, and 106b-5p) in paired CC tissues (tumor tissue vs. adjacent normal cervical tissue), CC cell lines, and human normal cervical epithelial immortalized cell line. A series of functional experiments were conducted to assess the function of hsa_circ_0107593 in CC development. The Receiver Operating Characteristic (ROC) curve was plotted to estimate the diagnostic value of hsa_circ_0107593 in CC. The dual-luciferase reporter assay was used to explore the interaction between hsa_circ_0107593 and hsa-miR-20a-5p/93-5p/106b-5p. Bioinformatic analysis was conducted to predict the target mRNAs, pathways, and functional enrichment. The results revealed that hsa_circ_0107593 has low expression in CC tissues and CC cell lines. Moreover, negative correlations of hsa_circ_0107593 expression were found against tumor diameter, FIGO stage, and myometrial invasion. Also, hsa_circ_0107593 impedes CC cell proliferation, migration, and invasion. Based on ROC curve analysis, hsa_circ_0107593 could serve as a diagnostic biomarker. Its low expression may indicate increased patient’s risk to developing cervical cancer. Mechanistically, hsa_circ_0107593 serves as a sponge of hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p. Collectively, our study implies that hsa_circ_0107593 has tumor-suppressing activity in CC by physically binding with hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p.

Author(s):  
He Zhu ◽  
Hongwei Zhang ◽  
Youliang Pei ◽  
Zhibin Liao ◽  
Furong Liu ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined. Methods Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1. Results Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC. Conclusions CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.


2016 ◽  
Vol 26 (5) ◽  
pp. 817-824 ◽  
Author(s):  
Quan Zhou ◽  
Ling R. Han ◽  
Yang X. Zhou ◽  
Yan Li

ObjectiveMicroRNAs (miRNAs) play crucial roles in cervical cancer development and progression. The purposes of this study were to investigate the role of miR-195 in cervical cancer and clarify the regulation of Smad3 by miR-195.MethodsQuantitative real-time polymerase chain reaction was used to examine miR-195 expression in cervical cancer tissues and cell lines. The clinicopathological significance of miR-195 down-regulation was further analyzed. Transwell migration and invasion assays were performed. A luciferase reporter assay was conducted to confirm the target gene of miR-195, and the results were validated in cervical cancer tissues and cell lines.ResultsMiR-195 was significantly decreased in clinical tissues and cervical cancer cell lines. The low miR-195 level was significantly correlated with higher International Federation of Gynecology and Obstetrics stage, node metastasis, and deep stromal invasion. Up-regulation of miR-195 suppressed cell migration and invasion in vitro. Smad3 was verified as a direct target of miR-195, which was further confirmed by the inverse expression of miR-195 and Smad3 in patients’ specimens.ConclusionsThe newly identified miR-195/Smad3 pathway provides an insight into cervical cancer metastasis and may represent a novel therapeutic target.


2018 ◽  
Vol 48 (1) ◽  
pp. 173-184 ◽  
Author(s):  
Jiamei Liu ◽  
Danbo Wang ◽  
Zaiqiu Long ◽  
Jing Liu ◽  
Weishan Li

Background/Aims: Circular RNAs (circRNAs) play a significant role in the development and progression of various human cancers. However, the expression and function of circRNAs in cervical cancer (CC) have rarely been explored. The aim of this study was to investigate the biological function of circRNA8924 in CC and elucidate the possible molecular mechanism involved. Methods: Quantitative polymerase chain reaction was used to determine mRNA expression of circRNA8924, miR-518d-5p/519-5p and CBX8 in CC tissues and cells. CBX8 protein expression was measured by Western blotting. The CCK-8 assay was used to evaluate cell proliferation, and the transwell assay to determine cell migration and invasion. The luciferase reporter assay was used to determine the direct regulation of miR-518d-5p/519-5p and circRNA8924 or CBX8 Results: The study demonstrated that the expression level of circRNA8924 in CC was significantly higher than that in the adjacent normal tissues (P < 0.001), and that it was also associated with tumor size, FIGO staging and myometrial invasion. The knockdown of circRNA8924 significantly inhibited the proliferation, migration and invasion of CC cells SiHa and HeLa. The expression level of miR-518d-5p/519-5p was negatively correlated with circRNA8924, and circRNA8924 regulated CBX8 by competitively binding to miR-518d-5p/519-5p. Conclusions: CircRNA8924 is highly expressed in CC tissue and can be considered a competitive endogenous RNA of the miR-518d-5p/519-5p family to promote the malignant biological behavior of CC cells. It is suggested that it may serve as a new biomarker for CC diagnosis and disease progression and provide potential targets for targeted therapy.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xia Chen ◽  
Jingxiu Yang ◽  
Yuping Wang

Abstract Background The long noncoding RNA (lncRNA) JPX is a molecular switch for X-chromosome inactivation. Accumulating studies have shown that the aberrant expression and function of lncRNAs are involved in the occurrence and development of tumors. However, the functional importance and mechanism of the action of lncRNA JPX in cervical cancer (CC) remain unknown. Method In this study, qRT-PCR and western blotting were used to evaluate the mRNA or protein expression of JPX, miR-25-3p and SOX4 in CC tissues and cell lines. StarBase v2.0 database, luciferase reporter assay and RNA immunoprecipitation assay were used to explore the relationship between JPX and miR-25-3p. EdU assay, CCK-8 assay and transwell assay were utilized to evaluate the proliferation, migration and invasion of CC cells. The tumor xenograft assay in nude mice was performed to demonstrate the role of the JPX/miR-25-3p/SOX4 axis in CC. Results We found that JPX was markedly upregulated, whereas miR-25-3p was markedly downregulated in CC tissues and cell lines, and the expression of JPX was negatively correlated with miR-25-3p in CC tissues. Moreover, overexpression of JPX increased proliferation, migration and invasion of HeLa cells, whereas knockdown of JPX decreased proliferation, migration and invasion of HeLa cells. In contrast to JPX, overexpression of miR-25-3p decreased proliferation, migration and invasion of HeLa cells. In addition, knockdown of JPX was found to inhibit HeLa cell viability and tumor development via up-regulating the expression of miR-25-3p and inhibiting the expression of SOX4. Conclusions Our study demonstrates that JPX promotes cervical cancer progression through modulating the miR-25-3p/SOX4 axis, and may serve as a potential target for CC therapy.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shaozheng Chen ◽  
Kejun Li

Abstract Background Long non-coding RNAs (LncRNAs) are dysregulated in multiple human cancers and they are highly involved in tumor progression. Previous studies have identified the oncogenic lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in human cancers, while its roles in cervical cancer (CC) remain unclear. Herein we intended to characterize the implication of HOXD-AS1 in CC. Methods qRT-PCR was applied to examine the relative expression of HOXD-AS1 in CC tissues, cell lines and transfected cells. Wound healing and transwell assays were applied to detect cell migration and invasion alteration. The targeting relationship between miRNA and mRNA/lncRNA was determined by dual luciferase reporter, qRT-PCR and western blot assays. Results HOXD-AS1 was overexpressed in CC tissues and cell lines. Its higher level predicted worse prognosis of CC patients. SiRNA mediated knockdown of HOXD-AS1 repressed CC cell migration and invasion, and its overexpression did the opposite. Mechanistically, HOXD-AS1 acted as a competing endogenous RNA (ceRNA) to sponge miR-877-3p and led to upregulation of FGF2, a target of miR-877-3p. Importantly, either miR-877-3p overexpression or FGF2 inhibition could abolish the migration and invasion promotion induced by HOXD-AS1. Conclusion HOXD-AS1 functions as a tumor-promoting lncRNA via the miR-877-3p/FGF2 axis in CC. HOXD-AS1 might be a promising therapeutic target as well as a novel prognostic biomarker for CC.


Author(s):  
Fei Ji ◽  
Delinaer Wuerkenbieke ◽  
Yan He ◽  
Yan Ding ◽  
Rong Du

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are a class of significant regulators in various tumorigenesis processes. The lncRNA homeobox transcript antisense RNA (HOTAIR) has been reported to act as a functional lncRNA in cervical cancer development. The present study investigated the underlying mechanism of HOTAIR and miR-17-5p in cervical cancer tumorigenesis. The results showed that HOTAIR expression was significantly upregulated in both cervical cancer tissues and cell lines. Loss-of-function experiments showed that HOTAIR knockdown inhibited the proliferation, migration, and invasion of cervical cells. In addition, miR-17-5p expression was downregulated in cervical cancer tissues and cell lines. Pearson’s correlation analysis indicated that miR-17-5p expression was negatively correlated to that of HOTAIR. Luciferase reporter assay revealed that miR-17-5p directly targeted HOTAIR 3′-UTR. Rescue experiments showed that miR-17-5p knockdown could reverse the tumor-suppressing effect caused by si-HOTAIR transfection. In summary, our results reveal the tumor-promoting role of HOTAIR in cervical cancer via sponging miR-17-5p, providing a novel therapeutic target for future treatment of cervical cancer.


2021 ◽  
Author(s):  
He Zhu ◽  
Hongwei Zhang ◽  
Youliang Pei ◽  
Zhibin Liao ◽  
Furong Liu ◽  
...  

Abstract Background: Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined.Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1.Results: Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC.Conclusions: CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.


2020 ◽  
Author(s):  
He Zhu ◽  
Hongwei Zhang ◽  
Youliang Pei ◽  
Zhibin Liao ◽  
Furong Liu ◽  
...  

Abstract Background: Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined.Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1.Results: Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC.Conclusions: CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.


2020 ◽  
Author(s):  
Hongjuan Yang ◽  
Xiangkun Li ◽  
Xinwei Zhao ◽  
Chang Wang ◽  
Dongyan Qin ◽  
...  

Abstract Background Cervical cancer (CC) is a common female cancer according to global cancer statistics. The current study was used to investigate the regulatory mechanism of circ_0000069 in CC. Methods The real-time quantitative polymerase chain reaction (RT-qPCR) was used to assess circ_0000069, miR-4429, and zinc finger protein of the cerebellum 2 (ZIC2) expression in CC tissues and cells. Kaplan-Meier analysis was performed in CC patients to analyze the relationship between survival time and circ_0000069 expression. The proliferation, apoptosis, cell cycle of CC cells were detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), colony formation, and flow cytometry analyses, respectively. In addition, western blot assay was employed to show expression levels of apoptosis/cell cycle-related proteins, as well as ZIC2. The migration and invasion of CC cells were assessed by transwell analysis. Possible target miRNAs of circ_0000069, along with the interaction between ZIC2 and miR-4429 were confirmed by pull-down and dual-luciferase reporter assays. Eventually, the functional role of circ_0000069 in vivo was clarified with the xenograft experiment in nude mice. Results Circ_0000069 was overexpressed in CC tissues and cells than controls. Furthermore, the silencing of circ_0000069 inhibited proliferation, migration, and invasion while included apoptosis and cell cycle arrest of CC cells, which was overturned by downregulation of miR-4429. Importantly, ZIC2 was a direct target of miR-4429 in CC cells, and we further confirmed that overexpression of miR-4429 suppressed CC progress by decreasing ZIC2 expression in CC cells. Surely, silencing of circ_0000069 inhibited tumorigenesis in vivo. Conclusion Our current results suggested that circ_0000069 exerted its tumorigenic roles by regulation of proliferation, apoptosis, cell cycle, migration, and invasion of CC cells, supporting that circ_0000069/miR-4429/ZIC2 axis may provide potential prognostic biomarkers for CC.


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