THU0243 HSA_CIRC_0123190 FUNCTIONS AS A COMPETITIVE ENDOGENOUS RNA TO REGULATE APLNR EXPRESSION BY SPONGING HSA-MIR-483-3P IN LUPUS NEPHRITIS

Background:Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs(circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases, such as, autoimmunity diseases. However, the role of circRNA in lupus nephritis has been rarely reported.Objectives:In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN.Methods:Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by RNA sequencing (RNA-seq). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Correlation analysis and receiver operating characteristic (ROC) curve were used to reveal the clinical value of selected circRNA, miRNA and mRNA. The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The degrees of renal fibrosis between the two groups were compared by Masson-trichome staining and immunohistochemistry staining.Results:159 circRNAs were significantly dysregulated in LN patients compared with NC group. The expression of hsa_circ_0123190 was significantly decreased in renal tissues of patients with LN (p=0.014), as same as the sequencing results. The area under the ROC curve of hsa_circ_0123190 in renal tissues was 0.820. Bio-informatic analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p which was also validated to interact with APLNR mRNA. APLNR mRNA expression was positively related with chronicity index (CI) of LN (R2=0.452,p=0.033). Finally, the factors of renal fibrosis, especially TGF-β (p=0.018), were more pronounced in the LN group.Conclusion:Hsa_circ_0123190 could function as a ceRNA to regulate APLNR expression involved in renal fibrosis by sponging hsa-miR-483-3p in LNReferences:[1]Aljaberi N, Bennett M, Brunner HI, Devarajan P. Proteomic profiling of urine: implications for lupus nephritis. Expert review of proteomics. 2019;16(4):303-13.[2]Zheng ZH, Zhang LJ, Liu WX, Lei YS, Xing GL, Zhang JJ, et al. Predictors of survival in Chinese patients with lupus nephritis. Lupus. 2012;21(10):1049-56.[3]Chen LL. The biogenesis and emerging roles of circular RNAs. Nature reviews Molecular cell biology. 2016;17(4):205-11.[4]Mahmoudi E, Cairns MJ. Circular RNAs are temporospatially regulated throughout development and ageing in the rat. Scientific reports. 2019;9(1):2564.[5]Liang D, Wilusz JE. Short intronic repeat sequences facilitate circular RNA production. Genes & development. 2014;28(20):2233-47.[6]Tan WL, Lim BT, Anene-Nzelu CG, Ackers-Johnson M, Dashi A, See K, et al. A landscape of circular RNA expression in the human heart. Cardiovascular research. 2017;113(3):298-309.[7]Zhao Z, Li X, Jian D, Hao P, Rao L, Li M. Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus. Acta diabetologica. 2017;54(3):237-45.[8]Ouyang Q, Huang Q, Jiang Z, Zhao J, Shi GP, Yang M. Using plasma circRNA_002453 as a novel biomarker in the diagnosis of lupus nephritis. Molecular immunology. 2018;101(undefined):531-8.[9]Luan J, Jiao C, Kong W, Fu J, Qu W, Chen Y, et al. CircHLA-C Plays an Important Role in Lupus Nephritis by Sponging miR-150. Molecular therapy Nucleic acids. 2018;10(undefined):245-53.[10]Kuschnerus K, Straessler ET, Müller MF, Lüscher TF, Landmesser U, Kränkel N. Increased Expression of miR-483-3p Impairs the Vascular Response to Injury in Type 2 Diabetes. Diabetes. 2019;68(2):349-60.[11]Huang Z, Wu L and Chen L. Apelin/APJ system: A novel potential therapy target for kidney disease. Journal of cellular physiology. 2018;233(5): 3892-900.Disclosure of Interests:None declared

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Hsa_circ_0123190 acts as a competitive endogenous RNA to regulate APLNR expression by sponging hsa-miR-483-3p in lupus nephritis

Arthritis Research & Therapy ◽

10.1186/s13075-020-02404-8 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Chunyi Zhang ◽

Congcong Gao ◽

Xueqi Di ◽

Siwan Cui ◽

Wenfang Liang ◽

...

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Circular Rnas ◽

Reporter Assay ◽

Clinical Value ◽

Chronicity Index

Abstract Background Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN. Methods Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining. Results 159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in the renal tissues of patients with LN (P = 0.014). Bio-informatics analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R2 = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-β1 (TGF-β1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018). Conclusion Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.

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Hsa_circ_0123190 acts as a competitive endogenous RNA to regulate APLNR expression by sponging hsa-miR-483-3p in lupus nephritis

10.21203/rs.3.rs-26778/v1 ◽

2020 ◽

Author(s):

Chunyi Zhang ◽

Congcong Gao ◽

Xueqi Di ◽

Siwan Cui ◽

Wenfang Liang ◽

...

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Circular Rnas ◽

Reporter Assay ◽

Clinical Value ◽

Chronicity Index

Abstract Background Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs(circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN. Methods Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining. Results 159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in renal tissues of patients with LN (P = 0.014). Bio-informatic analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R2 = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-β1 (TGF-β1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018). Conclusion Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.

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Hsa_circ_0123190 acts as a competitive endogenous RNA to regulate APLNR expression by sponging hsa-miR-483-3p in lupus nephritis

10.21203/rs.3.rs-26778/v2 ◽

2020 ◽

Author(s):

Chunyi Zhang ◽

Congcong Gao ◽

Xueqi Di ◽

Siwan Cui ◽

Wenfang Liang ◽

...

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Circular Rnas ◽

Reporter Assay ◽

Clinical Value ◽

Chronicity Index

Abstract Background: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs(circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN. Methods: Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining. Results: 159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in renal tissues of patients with LN (P =0.014). Bio-informatic analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P =0.033, R 2 =0.452). Moreover, the fibrotic-related protein, transforming growth factor-β1 (TGF-β1), which was regulated by APLNR, was more pronounced in the LN group (P =0.018). Conclusion: Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.

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Identification of Circulating hsa_circ_0063425 and hsa_circ_0056891 as Novel Biomarkers for Detection of Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab101 ◽

2021 ◽

Author(s):

Ya-Ke Lu ◽

Xi Chu ◽

Shuo Wang ◽

Yue Sun ◽

Jie Zhang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Early Detection ◽

Expression Profiles ◽

Akt Signaling ◽

Luciferase Reporter ◽

Circular Rnas ◽

Healthy Controls ◽

Mirna Targets ◽

Novel Biomarkers

Abstract Context Circular RNAs (circRNAs), which are involved in the development of diseases by regulating gene expression, have become promising novel biomarkers for diseases. Objective The aim of the present study was to identify the circulating circRNA biomarkers for early detection of type 2 diabetes (T2D). Methods The circRNA expression profiles were screened by microarray and compared between 5 new T2D cases and 5 healthy controls. The expression of candidate circRNAs that may be involved in the insulin phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway were validated by RT-qPCR in a second sample with 30 T2D cases and 30 controls. The association between circRNAs and T2D and their clinical significances were further assessed by logistic regression model, correlation analysis, and ROC curve in a large cohort comprising 313 subjects. The microRNA (miRNA) targets of circRNAs were verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results Low expressed circ_0063425 and hsa_circ_0056891 were independent predictors of T2D, impaired fasting glucose (IFG), and insulin resistance. The 2-circRNA panel had a high diagnostic accuracy for discriminating T2D and IFG from healthy controls, especially when body mass index was integrated. miR-19a-3p and miR-1-3p were identified as the miRNA targets of hsa_circ_0063425 and hsa_circ_0056891, respectively. Significant positive correlations were found between the expression levels of AKT and hsa_circ_0063425, PI3K and hsa_circ_0056891, in the total sample and subgroups stratified by glucose levels. Conclusion Downregulated hsa_circ_0063425 and hsa_circ_0056891 might contribute to the pathogenesis of T2D. They are valuable circulating biomarkers for early detection of T2D, which may be involved in regulation of PI3K/AKT signaling.

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Hsa_circ_0026628 promotes the development of colorectal cancer by targeting SP1 to activate the Wnt/β-catenin pathway

Cell Death and Disease ◽

10.1038/s41419-021-03794-6 ◽

2021 ◽

Vol 12 (9) ◽

Author(s):

Xuexiu Zhang ◽

Jianning Yao ◽

Haoling Shi ◽

Bing Gao ◽

Haining Zhou ◽

...

Keyword(s):

Colorectal Cancer ◽

Transcription Factor ◽

Circular Rna ◽

Luciferase Reporter ◽

Circular Rnas ◽

Transcriptional Level ◽

Sp1 Transcription Factor ◽

Reporter Assays ◽

Sphere Formation

AbstractCircular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including colorectal cancer (CRC). SP1 (Sp1 transcription factor) is a well-recognized oncogene in CRC and is deemed to trigger the Wnt/β-catenin pathway. The present study was designed to investigate the role of circRNAs which shared the same pre-mRNA with SP1 in CRC cells. We identified that hsa_circ_0026628 (circ_0026628), a circular RNA that originated from SP1 pre-mRNA, was upregulated in CRC cells. Sanger sequencing and agarose gel electrophoresis verified the circular characteristic of circ_0026628. Functional assays including CCK-8, colony formation, transwell, immunofluorescence staining, and sphere formation assay revealed the function of circ_0026628. RNA pull-down and mass spectrometry disclosed the proteins interacting with circ_0026628. Mechanistic assays including RIP, RNA pull-down, CoIP, ChIP, and luciferase reporter assays demonstrated the interplays between molecules. The results depicted that circ_0026628 functioned as a contributor to CRC cell proliferation, migration, EMT, and stemness. Mechanistically, circ_0026628 served as the endogenous sponge of miR-346 and FUS to elevate SP1 expression at the post-transcriptional level, thus strengthening the interaction between SP1 and β-catenin to activate the Wnt/β-catenin pathway. In turn, the downstream gene of Wnt/β-catenin signaling, SOX2 (SRY-box transcription factor 2), transcriptionally activated SP1 and therefore boosted circ_0026628 level. On the whole, SOX2-induced circ_0026628 sponged miR-346 and recruited FUS protein to augment SP1, triggering the downstream Wnt/β-catenin pathway to facilitate CRC progression.

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Circular RNA circCSPP1 knockdown attenuates doxorubicin resistance and suppresses tumor progression of colorectal cancer via miR-944/FZD7 axis

Cancer Cell International ◽

10.1186/s12935-021-01855-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lanlan Xi ◽

Quanlin Liu ◽

Wei Zhang ◽

Linshan Luo ◽

Jingfeng Song ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Growth ◽

Circular Rna ◽

Luciferase Reporter ◽

Circular Rnas ◽

Protein Levels ◽

Cell Progression ◽

Rna Immunoprecipitation ◽

Induced Apoptosis

Abstract Background Circular RNAs (circRNAs) have been reported to play vital roles in colorectal cancer (CRC). However, only a few circRNAs have been experimentally validated and functionally described. In this research, we aimed to reveal the functional mechanism of circCSPP1 in CRC. Methods 36 DOX sensitive and 36 resistant CRC cases participated in this study. The expression of circCSPP1, miR-944 and FZD7 were detected by quantitative real time polymerase chain reaction (qRT-PCR) and the protein levels of FZD7, MRP1, P-gp and LRP were detected by western blot. Cell proliferation, migration, invasion, and apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, or flow cytometry analysis, respectively. The interaction between miR-944 and circCSPP1 or frizzled-7 (FZD7) was predicted by Starbase 3.0 and verified by the dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay. Xenograft tumor assay was performed to examine the effect of circCSPP1 on tumor growth in vivo. Results The expression of circCSPP1 and FZD7 was upregulated while miR-944 expression was downregulated in doxorubicin (DOX)-resistant CRC tissues and cells. CircCSPP1 knockdown significantly downregulated enhanced doxorubicin sensitivity, suppressed proliferation, migration, invasion, and induced apoptosis in DOX-resistant CRC cells. Interestingly, we found that circCSPP1 directly downregulated miR-944 expression and miR-944 decreased FZD7 level through targeting to 3′ untranslated region (UTR) of FZD7. Furthermore, circCSPP1 mediated DOX-resistant CRC cell progression and doxorubicin sensitivity by regulating miR-944/FZD7 axis. Besides, circCSPP1 downregulation dramatically repressed CRC tumor growth in vivo. Conclusion Our data indicated that circCSPP1 knockdown inhibited DOX-resistant CRC cell growth and enhanced doxorubicin sensitivity by miR-944/FZD7 axis, providing a potential target for CRC therapy.

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Thymosin-β4 Mediates Hepatic Stellate Cell Activation by Interfering with CircRNA-0067835/miR-155/FoxO3 Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000495556 ◽

2018 ◽

Vol 51 (3) ◽

pp. 1389-1398 ◽

Cited By ~ 17

Author(s):

Lili Zhu ◽

Tingting Ren ◽

Zixin Zhu ◽

Mingliang Cheng ◽

Qiuju Mou ◽

...

Keyword(s):

Liver Fibrosis ◽

Cell Activation ◽

Stellate Cell ◽

Circular Rna ◽

Fine Tuning ◽

Differentially Expressed ◽

Luciferase Reporter ◽

Circular Rnas ◽

G1 Arrest

Background/Aims: Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis. Our study proved that thymosin beta 4 (Tβ4) has anti-fibrogenic effects in HSCs through PI3K/AKT pathway. However, the underlying mechanisms are not fully elucidated. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of in liver fibrosis is still unknown. Therefore, we hypothesize that Tβ4 influences circRNAs in liver fibrosis. Methods: Circular RNA microarray was conducted to identify Tβ4-related circRNAs. Pathway analysis and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in liver fibrosis. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in liver fibrosis. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in liver fibrosis. Results: A total of 644 differentially expressed circRNAs were identified between the Tβ4-depleted LX-2 cells and the control LX2 cells. The expression of circRNA-0067835 was significantly increased in the Tβ4-depleted LX-2 cells compared with control. Knockdown of circRNA-0067835 observably decreased LX-2 cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated liver fibrosis progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with liver fibrosis.

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Applying decision tree for detection of a low risk population for type 2 diabetes: A population based study

Medical Technologies Journal ◽

10.26415/2572-004x-vol1iss4p132-132 ◽

2017 ◽

Vol 1 (4) ◽

pp. 132-132

Author(s):

Habibollah Esmaeily ◽

Maryam Tayefi ◽

Hassan Doosti ◽

Majid Ghayour-Mobarhan ◽

Ali Reza Amirabadizadeh

Keyword(s):

Type 2 Diabetes ◽

Decision Tree ◽

Prediction Model ◽

Roc Curve ◽

Population Based ◽

Low Risk ◽

Tree Model ◽

Related Factors ◽

Study Program

Introduction: The aim of current study was to create a prediction model using data mining approach, decision tree technique, to identify low risk individuals for incidence of Type 2 diabetes (T2DM), using the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) Study program. Methods: a prediction model was developed using classification by the decision tree method on 9528 subjects recruited from MASHAD database. Moreover, the receiver operating characteristic (ROC) curve was applied. Results: The prevalence rate of T2DM was ~14% in our population. For decision tree model, the accuracy, sensitivity, and specificity value for identifying the related factors with T2DM were 78.7%, 47.8% and 83%, respectively. In addition, the area under the ROC curve (AUC) value for recognizing the risk factors associated with T2DM was 0.64. Moreover, we found that subjects with family history of T2DM, age>=48, SBP>=130, DBP>=81, HDL>=29, LDL>=148 and occupation=other have more than 59% chance of this disorder, while the chance of T2DM in subjects without history with TG>=184, age>=48 and hs-CRP>=2.2, have approximately 51% chance. Conclusion: Our findings demonstrated that decision tree analysis, using routine demographic, clinical, anthropometric and biochemical measurements, which combined with other risk score models, could create a simple strategy to predict individuals at low risk for type 2 diabetes in order to decrease substantially the number of subjects needing for screening and recognition of subject at high risk.

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Deep serum proteomics reveal biomarkers and causal candidates for type 2 diabetes

10.1101/633297 ◽

2019 ◽

Cited By ~ 1

Author(s):

Valborg Gudmundsdottir ◽

Valur Emilsson ◽

Thor Aspelund ◽

Marjan Ilkov ◽

Elias F Gudmundsson ◽

...

Keyword(s):

Type 2 Diabetes ◽

Serum Proteins ◽

Protein Profile ◽

Disease Onset ◽

Serum Levels ◽

The Body ◽

Protein Biomarkers ◽

Clinical Value ◽

Serum Proteomics

AbstractThe prevalence of type 2 diabetes mellitus (T2DM) is expected to increase rapidly in the next decades, posing a major challenge to societies worldwide. The emerging era of precision medicine calls for the discovery of biomarkers of clinical value for prediction of disease onset, where causal biomarkers can furthermore provide actionable targets. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach measuring serum levels of 4,137 proteins in 5,438 Icelanders to discover novel biomarkers for incident T2DM and describe the serum protein profile of prevalent T2DM. We identified 536 proteins associated with incident or prevalent T2DM. Through LASSO penalized logistic regression analysis combined with bootstrap resampling, a panel of 20 protein biomarkers that accurately predicted incident T2DM was identified with a significant incremental improvement over traditional risk factors. Finally, a Mendelian randomization analysis provided support for a causal role of 48 proteins in the development of T2DM, which could be of particular interest as novel therapeutic targets.

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Circular RNA circFAT1(e2) Promotes Colorectal Cancer Tumorigenesis via the miR-30e-5p/ITGA6 Axis

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/9980459 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Fei Pan ◽

Dongqing Zhang ◽

Na Li ◽

Mei Liu

Keyword(s):

Colorectal Cancer ◽

Circular Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Small Interfering Rnas ◽

Regulatory Relationship ◽

Downstream Target ◽

Normal Tissues

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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