Circular RNA circHIPK3 Promotes Cell Metastasis through miR-637/STAT3 Axis in Osteosarcoma

Recent studies have suggested that circular RNAs play an important role in the progression of various cancers. However, few studies have revealed the great value of circRNAs in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we performed experiments with the human OS cell lines and the results showed that the expression of circHIPK3 in OS cell lines was significantly upregulated compared to that in the normal cell line. In addition, the results showed that circHIPK3 could promote the migration, invasion, and growth of OS cells. Furthermore, miR-637 was identified as a target of circHIPK3, while STAT3 was targeted by miR-637. circHIPK3 could promote STAT3 expression via interacting with miR-637 in OS cells. In conclusion, our research uncovered an important role of the circHIPK3/miR-637/STAT3 pathway in the migration and invasion of OS cells and suggested that circHIPK3 may be a prognostic marker and a promising therapeutic target for OS.

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Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer

10.21203/rs.3.rs-26944/v2 ◽

2020 ◽

Author(s):

Liang Jing ◽

Junhui Wu ◽

Xiaocheng Tang ◽

Min Ma ◽

Fei Long ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Lines ◽

Tumor Stage ◽

Circular Rna ◽

Gene Expression Omnibus ◽

Migration And Invasion ◽

Circular Rnas ◽

Normal Tissues ◽

Node Metastasis

Abstract Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. Methods: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines.Results:Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression.Conclusion: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

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Identification of circular RNA hsa_circ_0044556 and its effect on the development and progression of colorectal cancer

10.21203/rs.3.rs-26944/v1 ◽

2020 ◽

Author(s):

Liang Jing ◽

Junhui Wu ◽

Xiaocheng Tang ◽

Min Ma ◽

Fei Long ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Lines ◽

Tumor Stage ◽

Circular Rna ◽

Gene Expression Omnibus ◽

Migration And Invasion ◽

Circular Rnas ◽

Normal Tissues ◽

Node Metastasis

Abstract Background Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNAs in the development and progression of colorectal cancer (CRC) remains unclear. Methods First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines. Results hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression. Conclusion hsa_circ_0044556 promoted the development and progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

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Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer

10.21203/rs.3.rs-26944/v3 ◽

2020 ◽

Author(s):

Liang Jing ◽

Junhui Wu ◽

Xiaocheng Tang ◽

Min Ma ◽

Fei Long ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Lines ◽

Tumor Stage ◽

Circular Rna ◽

Gene Expression Omnibus ◽

Migration And Invasion ◽

Circular Rnas ◽

Normal Tissues ◽

Node Metastasis

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Circ_0000215 Exerts Oncogenic Function in Nasopharyngeal Carcinoma by Targeting miR-512-5p

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.688873 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xinping Chen ◽

Weihua Xu ◽

Zhichao Ma ◽

Juan Zhu ◽

Junjie Hu ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cell Lines ◽

Cell Counting ◽

Regulatory Subunit ◽

Luciferase Reporter ◽

Regulatory Function ◽

Migration And Invasion ◽

Circular Rnas

Background: Increasing circular RNAs (circRNAs) are reported to participate in cancer progression. Nonetheless, the role of circRNAs in nasopharyngeal carcinoma (NPC) has not been fully clarified. This work is aimed to probe the role of circ_0000215 in NPC.Methods: Circ_0000215 expression in NPC tissues and cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay, 5-bromo-2′-deoxyuridine (BrdU) assay, scratch healing assay and Transwell experiment were executed to investigate the regulatory function of circ_0000215 on the proliferation, migration and invasion of NPC cells. RNA immunoprecipitation (RIP), pull-down and dual-luciferase reporter experiments were utilized to determine the binding relationship between circ_0000215 and miR-512-5p, and between miR-512-5p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) 3′UTR. The effects of circ_0000215 on NPC growth and metastasis in vivo were examined with nude mice model. Western blot was applied to detect the regulatory effects of circ_0000215 and miR-512-5p on PIK3R1 expression.Results: Circ_0000215 was overexpressed in NPC tissues and cell lines. The functional experiments confirmed that knockdown of circ_0000215 impeded the growth and metastasis of NPC cells in vitro and in vivo. Additionally, circ_0000215 could also work as a molecular sponge to repress miR-512-5p expression. PIK3R1 was validated as a target gene of miR-512-5p, and circ_0000215 could increase the expression level of PIK3R1 in NPC cells via suppressing miR-512-5p.Conclusion: Circ_0000215 is overexpressed in NPC and exerts oncogenic effects in NPC through regulating miR-512-5p/PIK3R1 axis.

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Circular RNA hsa_circ_0081343 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-210-5p/DLX3 axis

10.21203/rs.3.rs-361692/v1 ◽

2021 ◽

Author(s):

Jiansheng Xie ◽

Hui Wang ◽

Caiqun Luo ◽

Xiaoxia Wu ◽

Jianming Zhang ◽

...

Keyword(s):

Luciferase Activity ◽

Circular Rna ◽

Extravillous Trophoblast ◽

Migration And Invasion ◽

Circular Rnas ◽

Protein Levels ◽

Apoptosis Protein ◽

Luciferase Activity Assay ◽

Rna Immunoprecipitation

Abstract Background: Various circular RNAs (circRNAs) are dysregulated in the placenta of fetal growth restriction fetuses, but their role and regulatory mechanisms have not been fully elucidated. Herein, we aimed to elucidate the role of hsa_circ_0081343 in regulating the migration, invasion, and apoptosis in the human extravillous trophoblast HTR-8 cells.Methods: circRNA and miRNA levels were examined using quantitative real-time PCR (RT-PCR). Overexpression plasmid constructs and siRNA were used to overexpress and knockdown hsa_circ_0081343, respectively. Transwell assay and flow cytometry analysis were performed to evaluate the effect of hsa_circ_0081343 or miR-210-5p on migration, invasion, and apoptosis. Protein levels were analyzed using western blot. Dual luciferase activity assay and anti-AGO2 RNA immunoprecipitation (RIP) assays were performed to identify the relationship between miR-210-5p and hsa_circ_0081343.Results: Hsa_circ_0081343 expression was significantly downregulated in 37 FGR placental tissues as compared to healthy placental control tissues. Hsa_circ_0081343 overexpression possibly inhibits apoptosis by downregulating the expression of cleaved caspase 3 and caspase 9 and alleviates the migration and invasion of HTR-8 cells by inducing the expression of MMP2 and MMP9. The dual luciferase activity and anti-AGO2 RIP assay results showed that hsa_circ_0081343 binds to miR-210-5p. miR-210-5p overexpression eliminated the effect of hsa_circ_0081343 overexpression in HTR-8 cells. Finally, DLX3 was identified as a direct target of miR-210-5p. Conclusions: Hsa_circ_0081343 regulates the migration, invasion, and apoptosis of HTR-8 cells via the hsa-miR-210-5p/DLX3 axis. Thus, hsa_circ_0081343 plays a key role in the etiology and pathogenesis of FGR implicating its importance as a novel candidate for targeted FGR therapy.

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Circular RNA hsa_circ_0001829 promotes gastric cancer progression through miR-155-5p/SMAD2 axis

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01790-w ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Qiuling Niu ◽

Zhijie Dong ◽

Min Liang ◽

Yuanwei Luo ◽

Hai Lin ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Lines ◽

Cancer Progression ◽

Cell Cycle Progression ◽

Luciferase Assay ◽

Migration And Invasion ◽

Circular Rnas ◽

Gain Of Function

Abstract Background Accumulating evidences have shown that circular RNAs (circRNAs) play important roles in regulating the pathogenesis of cancer. However, the role of circRNAs in gastric cancer (GC) remains largely unclear. Methods In this study, we identified a novel upregulated circRNA, hsa_circ_0001829, in chemically induced malignant transformed human gastric epithelial cells using RNA-seq. Subsequent qRT-PCR and ISH assays were performed to detect the expression level of hsa_circ_0001829 in GC cell lines and tissues. Functional roles of hsa_circ_0001829 in GC were then explored by loss- and gain-of- function assays. Bioinformatic prediction and luciferase assay were used to investigate potential mechanisms of hsa_circ_0001829. Finally, the mice xenograft and metastasis models were constructed to assess the function of hsa_circ_0001829 in vivo. Results We found that hsa_circ_0001829 was significantly upregulated in GC tissues and cell lines. Loss- and gain-of- function assays showed that hsa_circ_0001829 promotes GC cells proliferation, migration and invasion, and the affected cell cycle progression and apoptosis rates may account for the effect of hsa_circ_0001829 on GC proliferation. In addition, bioinformatic prediction and luciferase assay showed that hsa_circ_0001829 acts as a molecular sponge for miR-155-5p and that SMAD2 was a target gene of miR-155-5p; moreover, hsa_circ_0001829 sponges miR-155-5p to regulate SMAD2 expression and hsa_circ_0001829 promotes GC progression through the miR-155-5p–SMAD2 pathway. Finally, suppression of hsa_circ_0001829 expression inhibited tumor growth and aggressiveness in vivo. Conclusion Taken together, our findings firstly demonstrated a novel oncogenic role of hsa_circ_0001829 in GC progression through miR-155-5p–SMAD2 axis, and our study may offer novel biomarkers and therapeutic targets for GC.

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Exosomal circRNAs: new players in the field of cholangiocarcinoma

Clinical Science ◽

10.1042/cs20190940 ◽

2019 ◽

Vol 133 (21) ◽

pp. 2239-2244 ◽

Cited By ~ 3

Author(s):

Corentin Louis ◽

Matthis Desoteux ◽

Cédric Coulouarn

Keyword(s):

Cell Lines ◽

Molecular Mechanisms ◽

Human Tumor ◽

Direct Interaction ◽

Circular Rna ◽

Circular Rnas ◽

Loss Of Function ◽

Non Invasive ◽

Tumor Tissues

Abstract Cholangiocarcinoma (CCA) is a deadly cancer worldwide associated with limited therapeutic options. A recent study published in Clinical Science by Wang and colleagues [Clin. Sci. (2019) 133(18), 1935–1953] brought new perspectives to CCA management and therapy by focusing on circular RNAs (circRNAs). CircRNAs belong to an emerging class of functional non-coding RNAs (ncRNAs) regulating numerous biological processes. Notably, circRNAs have been associated with cancer onset and progression, although reports in CCA are very limited so far. In this work, the expression of circular RNA circ-0000284 (aka circHIPK3) was specifically elevated in CCA cell lines, human tumor tissues and plasma exosomes. Gain and loss of function approaches were performed to better understand the molecular mechanisms regulated by circ-0000284. Notably, the authors evaluated the role of circ-0000284 as a microRNA (miRNA) sponge. By prediction analysis and functional tests, a direct interaction was demonstrated with miR-637 that targets lymphocyte antigen-6 E (LY6E). Increased expression of circ-0000284 was associated with enhanced migration, invasion and proliferation of CCA cell lines. Interestingly, exosomal-mediated circ-0000284 was reported to exhibit pro-oncogenic effects on surrounding normal cells. Altogether, these data highlight circRNAs not only as new players in CCA pathogenesis but also as promising molecules for innovative non-invasive biomarkers, as circRNAs are enriched and stable in exosomes. Further investigations on extracellular vesicles should provide the necessary tools to improve CCA diagnosis, and move toward targeted-therapies.

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Circular RNA hsa_Circ_101141 as a Competing Endogenous RNA Facilitates Tumorigenesis of Hepatocellular Carcinoma by Regulating miR-1297/ROCK1 Pathway

Cell Transplantation ◽

10.1177/0963689720948016 ◽

2020 ◽

Vol 29 ◽

pp. 096368972094801 ◽

Cited By ~ 1

Author(s):

Tao Zhang ◽

Lijuan Zhang ◽

Dan Han ◽

Kebinur Tursun ◽

Xiaobo Lu

Keyword(s):

Hepatocellular Carcinoma ◽

Coiled Coil ◽

Circular Rna ◽

Migration And Invasion ◽

Circular Rnas ◽

Competing Endogenous Rna ◽

Direct Target ◽

And Function

As a novel class of noncoding RNAs, circular RNAs (circRNAs) have been recently reported to be involved in cell development and function. However, the functional role of circRNAs in hepatocellular carcinoma (HCC) remains unclear. In the present study, we found that the expression of human circ_101141 was upregulated in HCC tissues and cells. In addition, downregulation of circ_101141 dramatically inhibited cell proliferation, migration, and invasion in HCC cells. In addition, by using the bioinformatics tools, the potential target of circ_101141 was predicted. Mechanistic investigations indicated that circ_101141 acted as a miR-1297 “sponge”; meanwhile, Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) was a direct target of miR-1297. Further experiments demonstrated that circ_101141 contributed to the progression of HCC by acting as competing endogenous RNA (ceRNA) of miR-1297 to regulate ROCK1 expression. Furthermore, knockdown of circ_101141 attenuated HCC tumorigenesis in vivo. Taken together, these findings indicated that circRNA circ_101141 acted as a ceRNA to facilitate tumorigenesis of HCC by regulating miR-1297/ROCK1 pathway.

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Circular RNA Circ0021205 Promotes Cholangiocarcinoma Progression Through MiR-204-5p/RAB22A Axis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.653207 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jianfei Tu ◽

Weiqian Chen ◽

Liyun Zheng ◽

Shiji Fang ◽

Dengke Zhang ◽

...

Keyword(s):

Cancer Progression ◽

Circular Rna ◽

Migration And Invasion ◽

Circular Rnas ◽

Diagnostic Biomarker ◽

Multiple Cancer ◽

Biliary Tract Tumors ◽

Oncogenic Function

Cholangiocarcinomas (CCA) are biliary tract tumors that are often challenging to diagnosis and treatment. Accumulated evidence reveals that circular RNAs (circRNAs) are involved in multiple cancer progression. However, the function of circRNAs in cholangiocarcinoma remains largely unclear. In this study, we found that circ_0021205 expression was up-regulated in CCA and positively correlated with tumor size and TNM stage. To further explore the role of circ_0021205 in CCA, cell functional assays were performed. The results showed that circ_0021205 promoted the proliferation, migration, and invasion of CCA cells. In vivo experiments showed that circ_0021205 inhibition reduced tumorigenesis in mice. In addition, mechanisms investigation demonstrated that circ_0021205 exerts its oncogenic function by sponging miR-204-5p to regulate the expression of RAB22A. Overall, this study revealed that circ_0021205 might serve as a potential diagnostic biomarker or therapeutic target for CCA.

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Circular RNA circ-CCAC1 Facilitates Adrenocortical Carcinoma Cell Proliferation, Migration, and Invasion through Regulating the miR-514a-5p/C22orf46 Axis

BioMed Research International ◽

10.1155/2020/3501451 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Wei Li ◽

Rengong Liu ◽

Dongmei Wei ◽

Wei Zhang ◽

Heyan Zhang ◽

...

Keyword(s):

Cell Lines ◽

Adrenocortical Carcinoma ◽

Circular Rna ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Loss Of Function ◽

Tissue Samples ◽

Tissue Specimens

Adrenocortical carcinoma (ACC) is a rare but clinically aggressive endocrine malignancy. Circular RNAs (circRNAs) were found to play key roles in tumorigenesis. In the current study, we aimed to investigate the functions and mechanisms of a novel circRNA, circ-CCAC1, in ACC cells. circ-CCAC1 expression levels in ACC tissue specimens and cell lines were evaluated by RT-qPCR. Kaplan-Meier analysis was applied to explore the relationship between circ-CCAC1 and patients’ prognosis. Cell counting kit-8 (CCK-8), colony formation, acridine orange/ethidium bromide (AO/EB) double fluorescence staining, and Transwell assays were performed to evaluate the functions of circ-CCAC1 in ACC cells. Bioinformatics analysis and a dual-luciferase reporter assay were utilized to explore the mechanisms of circ-CCAC1. As a result, circ-CCAC1 was overexpressed in ACC tissue samples and cell lines and correlated with poor prognosis. Gain- and loss-of-function tests demonstrated that circ-CCAC1 acted as an oncogene in ACC. What is more, circ-CCAC1 enhanced C22orf46 expression by sponging miR-514a-5p in ACC cells. A rescue assay illustrated that circ-CCAC1 facilitated ACC progression through miR-514a-5p/C22orf46 signaling. To sum up, we identified a novel circRNA, circ-CCAC1, which may be used as a potential therapeutic target for ACC.

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