Circular RNA circ_103820 suppresses lung cancer tumorigenesis by sponging miR-200b-3p to release LATS2 and SOCS6

circRNAs (circular RNAs) are a family of noncoding RNAs and have diverse physiological and pathological functions. However, the functions and mechanisms of circRNAs in the development and progression of colorectal cancer (CRC) remain largely unknown. Here, we aimed to explore the functions and roles of circFAT1(e2) in CRC. qRT-PCR revealed that circFAT1(e2) in CRC tumor tissues was upregulated compared with that in adjacent normal tissues and was also upregulated in CRC cell lines. Small interfering RNAs (siRNAs) against circFAT1(e2) were used to decrease the expression of circFAT1(e2) in HCT116 and RKO cells in vitro. The roles of circFAT1(e2) in CRC cell metastasis and proliferation were then determined by transwell and CCK-8 assays. The results showed that circFAT1(e2) silencing markedly suppressed CRC growth. Moreover, we identified circFAT1(e2) as a promoter of CRC metastasis. Knockdown of circFAT1(e2) evidently reduced HCT116 and RKO cell migration and invasion. Furthermore, the regulatory relationship between circFAT1(e2) and its target miRNAs was verified by a luciferase reporter assay. We demonstrated that circFAT1(e2) could sponge miR-30e-5p, which regulated the expression level of integrin α6 (ITGA6), the downstream target gene of miR-30e-5p. Rescue assays demonstrated that knockdown of miR-30e-5p enhanced CRC proliferation and migration via ITGA6. Taken together, our results reveal the novel oncogenic roles of circFAT1(e2) in CRC through the miR-30e-5p/ITGA6 axis.

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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 otx2 target genes and restrictions in ectodermal competence during Xenopus cement gland formation

Development ◽

10.1242/dev.124.2.471 ◽

1997 ◽

Vol 124 (2) ◽

pp. 471-481 ◽

Cited By ~ 8

Author(s):

L.S. Gammill ◽

H. Sive

Keyword(s):

Retinoic Acid ◽

Target Genes ◽

Homeobox Gene ◽

Cement Gland ◽

Inhibitory Effects ◽

Temporal Modulation ◽

Downstream Target ◽

Positional Identity ◽

Direct Target ◽

Differentiation Marker

The homeobox gene otx2 is a key regulator of positional identity in vertebrates, however its downstream target genes and mechanism of action are not known. We have analyzed otx2 function during formation of the Xenopus cement gland, an organ that expresses otx2. The cement gland forms at early neurula from extreme anterior ectoderm and corresponds to the chin primordium of mammals. Previous studies (Blitz, I. and Cho, K. (1995) Development 121, 993–1004; Pannese, M., Polo, C., Andreazzoli, M., Vignali, R., Kablar, B., Barsacchi, G. and Boncinelli, E. (1995) Development 121, 707–720) showed that misexpressed otx2 could activate cement gland formation. However, it was not clear whether this was a direct effect of otx2 or a secondary consequence of other tissues induced by otx2. In this study we ask whether otx2 activity is spatially and temporally restricted in the ectoderm and whether cement gland-specific genes are direct targets of otx2. In order to control the timing of otx2 activity, we constructed a dexamethasone-inducible otx2 protein (otx2-GR) by fusion with the ligand-binding domain of the glucocorticoid receptor. We conclude first, that regionally restricted factors regulate otx2 activity since otx2-GR is able to activate the cement gland markers XCG and XAG only in ventrolateral ectoderm, and never in the neural plate. Second, we show that temporal responsiveness of the ectoderm to otx2-GR is limited, beginning only at mid-gastrula but continuing as late as tailbud stages. Third, we show that otx2-GR activates expression of the cement gland differentiation marker XCG in the absence of protein synthesis, identifying a direct target of otx2. otx2-GR can also activate expression of the endogenous otx2 gene, defining an autoregulatory loop. Fourth, we show that otx2-GR is sufficient to overcome the inhibitory effects of retinoic acid on cement gland formation, indicating that this effect is caused by failure to express otx2. Corroboratively, we show that otx2 autoactivation is prevented by retinoic acid. Together, these findings suggest that otx2 directly controls cement gland differentiation, and that spatial and temporal modulation of otx2 activity limits cement gland formation to the front of the embryo.

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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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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

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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CircRNA hsa_circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway

Cell Death and Disease ◽

10.1038/s41419-020-03276-1 ◽

2020 ◽

Vol 11 (12) ◽

Author(s):

Guanqun Huang ◽

Min Liang ◽

Haiyan Liu ◽

Jianhong Huang ◽

Peiqing Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Expression Patterns ◽

Circular Rna ◽

Migration And Invasion ◽

Circular Rnas ◽

Biological Functions ◽

Competing Endogenous Rna ◽

Direct Target

AbstractCircular RNAs (circRNAs) have confirmed to participate in diverse biological functions in cancer. However, the expression patterns of circRNAs on hepatocellular carcinoma (HCC) remains unclear. In the present study, we clarified that hsa_circRNA_104348 was dramatically upregulated in HCC tissues and cells. Patients with HCC displaying high hsa_circRNA_104348 level possessed poor prognosis. Has_circ_104348 facilitated proliferation, migration, and invasion, meanwhile suppressed apoptosis of HCC cell. Furthermore, hsa_circRNA_104348 directly targeted miR-187–3p, could regulate miR-187-3p to affect proliferation, migration, invasion, and apoptosis of HCC cells, and may have effect on Wnt/β-catenin signaling pathway. Moreover, RTKN2 could be a direct target of miR-187-3p. In addition, knockdown of hsa_circRNA_104348 attenuated HCC tumorigenesis and lung metastasis in vivo. Taken together, these findings indicated that circular RNA hsa_circRNA_104348 might function as a competing endogenous RNA (ceRNA) to promotes HCC progression by targeting miR-187–3p/RTKN2 axis and activating Wnt/β-catenin pathway.

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Circular RNA Circ_0000098 Elevates ALX4 Expression via Adsorbing miR-1204 to Inhibit the Progression of Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.696078 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ming Li ◽

Wenjing Yue ◽

Qiankun Li ◽

Wenyu Yu ◽

Yao Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Circular Rna ◽

Gene Expression Omnibus ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Mesenchymal Transition ◽

Hcc Cells

BackgroundCircular RNAs (CircRNAs) feature prominently in the progression of various cancers. However, the biological functions of many circRNAs in hepatocellular carcinoma (HCC) are far from fully clarified. This work is performed to decipher the function of circ_0000098 (circSLC30A7) in modulating the progression of HCC and its molecular mechanism.MethodsMicroarray data (GSE97332) were available from the Gene Expression Omnibus (GEO) database, and circRNA differentially expressed in HCC tissues was screened out by GEO2R tool. Circ_0000098, microRNA-1204 (miR-1204), and aristaless-like homeobox-4 (ALX4) mRNA expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), scratch wound healing, and Transwell assays were adopted to determine proliferation, migration, and invasion of HCC cells. ALX4 protein, E-cadherin, N-cadherin, and Vimentin expressions were evaluated by Western blot. In addition, the targeting relationship between miR-1204 and circ_0000098 or ALX4 was studied with dual-luciferase reporter assay and RIP assay.ResultsCirc_0000098 expression level was markedly declined in HCC tissues and cells, and its underexpression was associated with larger tumor size of HCC patients. Knocking down circ_0000098 observably promoted the multiplication, migration, invasion, and epithelial-mesenchymal transition (EMT) of Huh7 and SMMC-7721 cells. Additionally, circ_0000098 was mainly distributed in the cytoplasm of HCC cells, and up-regulated ALX4 expression through competitively decoying miR-1204.ConclusionCirc_0000098, as a competitive endogenous RNA (ceRNA) of miR-1204, upregulates ALX4 expression and suppresses the growth, migration, invasion, and EMT of HCC cells.

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LncRNA MAFG-AS1 regulates miR-125b-5p/SphK1 axis to promote the proliferation, migration, and invasion of bladder cancer cells

Human Cell ◽

10.1007/s13577-020-00470-3 ◽

2021 ◽

Author(s):

Chenye Tang ◽

Yuntao Wu ◽

Xiao Wang ◽

Kean Chen ◽

Zhiling Tang ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Migration And Invasion ◽

Inhibitory Effects ◽

Potential Therapeutic Target ◽

Downstream Target ◽

Transwell Invasion Assay ◽

Tumor Tissues ◽

Bladder Cancer Cells ◽

Luciferase Activity Assay

AbstractMAFG-AS1 is an oncogenic lncRNA in multiple types of cancer. However, its role in bladder cancer (BC) remains unclear. The present study aimed to investigate the function of MAFG-AS1 in BC. BC and paired non-tumor tissues were collected. Two BC cell lines HT01197 and HT-1376 were used. Dual luciferase activity assay, RT-qPCR, western blot, CCK-8, transwell invasion assay, and wound healing assay were performed. We found that MAFG-AS1 was significantly up-regulated in BC tissues and predicted a poor survival rate. MAFG-AS1 interacted with miR-125b-5p. However, the expression levels of MAFG‑AS1 and miR-125b-5p were not obviously correlated in BC tissues, and MAFG‑AS1 and miR-125b-5p did not regulate the expression of each other. Interestingly, we found that SphK1, a downstream target of miR-125b-5p, was negatively correlated with miR-125b-5p, while it was positively correlated with MAFG-AS1 across BC tissues. In addition, overexpression of MAFG‑AS1 upregulated the expression of SphK1 in BC cells, and attenuated the inhibitory effects of miR-125b-5p on the expression of SphK1. Functional assays showed that overexpression of MAFG‑AS1 promoted BC cell proliferation, migration, and invasion, while its effects were attenuated by overexpression of miR-125b-5p. Moreover, overexpression of miR-125b-5p inhibited BC cell proliferation, migration, and invasion, while its effects were alleviated by overexpression of SphK1. Taken together, our findings demonstrated that MAFG-AS1 has an oncogenic role in BC by regulating the miR-125b-5p/SphK1 axis. MAFG-AS1 might serve as a good diagnostic marker and a potential therapeutic target of BC.

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A circular RNAs dataset landscape reveals potential signatures for the detection and prognosis of early-stage lung adenocarcinoma

BMC Cancer ◽

10.1186/s12885-021-08293-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhiying Chen ◽

Jiahui Wei ◽

Min Li ◽

Yongjuan Zhao

Keyword(s):

Functional Analysis ◽

Survival Analysis ◽

Lung Adenocarcinoma ◽

Target Genes ◽

Interaction Analysis ◽

Early Stage ◽

Gene Interaction ◽

Gene Expression Omnibus ◽

Circular Rnas ◽

Cerna Network

Abstract Background This study aimed to identify potential circular ribonucleic acid (circRNA) signatures involved in the pathogenesis of early-stage lung adenocarcinoma (LAC). Methods The circRNA sequencing dataset of early-stage LAC was downloaded from the Gene Expression Omnibus database. First, the differentially expressed circRNAs (DEcircRNAs) between tumour and non-tumour tissues were screened. Then, the corresponding miRNAs and their target genes were predicted. In addition, prognosis-related genes were identified using survival analysis and further used to build a network of competitive endogenous RNAs (ceRNAs; DEcircRNA–miRNA–mRNA). Finally, the functional analysis and drug–gene interaction analysis of mRNAs in the ceRNA network was performed. Results A total of 35 DEcircRNAs (30 up-regulated and 5 down-regulated circRNAs) were identified. Moreover, 135 DEcircRNA–miRNA and 674 miRNA–mRNA pairs were predicted. The survival analysis of these target mRNAs revealed that 60 genes were significantly associated with survival outcomes in early-stage LAC. Of these, high levels of PSMA 5 and low levels of NAMPT, CPT 2 and TNFSF11 exhibited favourable prognoses. In addition, the DEcircRNA–miRNA–mRNA network was constructed, containing 5 miRNA–circRNA (hsa_circ_0092283/hsa-miR-762/hsa-miR-4685-5p; hsa_circ_0070610/hsa-let-7a-2-3p/hsa-miR-3622a-3p; hsa_circ_0062682/hsa-miR-4268) and 60 miRNA–mRNA pairs. Functional analysis of the genes in the ceRNA network showed that they were primarily enriched in the Wnt signalling pathway. Moreover, PSMA 5, NAMPT, CPT 2 and TNFSF11 had strong correlations with different drugs. Conclusion Three circRNAs (hsa_circ_0062682, hsa_circ_0092283 and hsa_circ_0070610) might be potential novel targets for the diagnosis of early-stage LAC.

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