scholarly journals Circular RNA circ-PAN3 (hsa_circ_0100181) Promotes Hepatocellular Carcinoma Growth Through Sponging miR-153 to Elevate Cyclin D1 Expression

2020 ◽  
Author(s):  
Shuo Yu ◽  
Min Wang ◽  
Xu Li ◽  
Xingjun Guo ◽  
Renyi Qin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Cyclin D1 ◽  
Colony Formation ◽  
Xenograft Model ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Circular Rnas

Abstract Background: Circular RNAs (circRNAs) are engaged in hepatocellular carcinoma (HCC) progression, but the mechanisms remain to be elucidated. This study aimed to unveil the expression pattern and potential biological mechanisms of a newly indentified circRNA, circ-PAN3, in HCC. Methods: Cell Counting Kit-8 (CCK‐8) assay and colony formation assay were used to assess cell proliferation. Transcription-quantitative PCR (RT-qPCR) analysis and western blot analysis were used to determine the relative expression level of mRNA and protein, respectively. Cell apoptosis assay was used to evaluate the apoptosis rate of transfected cells. CircInteractome and Targetscan were utilized to predict the possible targets of circRNAs and miRNAs, respectively. Luciferase reporter assay and RNA pull-down assay were used to assess the direct interaction of RNAs. HCC cancer xenograft model was used to evaluate the biological process of circ-PAN3 in vivo. Student’s t test, χ2 test or one-way ANOVA was adopted appropriately.Results: Circ-PAN3 was elevated in HCC tissues, and patients with high Circ-PAN3 expression had a poor survival outcome. Knockdown of circ-PAN3 expression suppressed cell viability, colony formation and cell proliferation in vitro and in vivo. Circ-PAN3 elevates cyclin D1 expression to promote HCC progression. Subsequently, using CircInteractome, miR-153 were confirmed to interact with circ-PAN3 and was downregulated by circ-PAN3. Further, using Targetscan, cyclin D1 was validated to interact with miR-153 and was downregulated by miR-153. Addition of miR-153 expression with corresponsive mimics significantly reduced the expression of cyclin D1. Notably, the inhibition of cell viability, colony formation and proliferation induced by knockdown of circ-PAN3 were recovered following the combination with miR-153 inhibitor, cyclin D1, respectively. Conclusion: Together, this study demonstrated that a novel circ-PAN3/miR-153/cyclin D1 axis regulatory axis that promoted HCC progression.

scholarly journals Circ_0015756 aggravates hepatocellular carcinoma development by regulating FGFR1 via sponging miR-610

2020 ◽  
Author(s):  
Weisheng Guo ◽  
Lin Zhao ◽  
Yaguang Wei ◽  
Peng Liu ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Viability ◽  
Colony Formation ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Therapeutic Effects

Abstract Background: Hepatocellular carcinoma (HCC) is the leading threat of cancer-related death in humans with poor therapeutic effects. Circular RNAs (circRNAs) are important indicators in cancer diagnosis and prognosis. This study intended to explore the function and mechanism of circ_0015756 in HCC, providing the additional opinion for HCC treatment.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of circ_0015756 and miR-610. Cell viability was assessed by cell counting kit-8 (CCK-8) assay, and colony formation capacity was ascertained by colony formation assay. Cell proliferation and invasion were monitored by transwell assay. Cell cycle progression and apoptosis were analyzed by flow cytometry assay. Circ_0015756 oncogenicity was determined by Xenograft models. The prediction of targets was performed using the bioinformatics tools, and the verification of targeted relationship was conducted using RNA pull-down, RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. The expression level of fibroblast growth factor receptor 1 (FGFR1) was measured by western blot.Result: The expression of circ_0015756 was increased in HCC tissues, serums and cells. Circ_0015756 downregulation impaired HCC cell viability, colony formation capacity, invasion and migration, induced cell cycle arrest and apoptosis, and inhibited tumor growth in vivo. MiR-610 was ensured as a target of circ_0015756, and miR-610 absence reversed the effects of circ_0015756 downregulation. Further, FGFR1 was interacted by miR-610, and FGFR1 overexpression overturned the effects of miR-610 restoration in vitro. Circ_0015756 could regulate FGFR1 expression by targeting miR-610.Conclusion: Circ_0015756 played its tumorigenic properties in HCC by activating FGFR1 and sponging miR-610, and circ_0015756 was expected to be a vital indicator in HCC diagnosis and treatment.

scholarly journals CircARVCF Contributes to Cisplatin Resistance in Gastric Cancer by Altering miR-1205 and FGFR1

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruirui Zhang ◽  
Huanyu Zhao ◽  
Hongmei Yuan ◽  
Jian Wu ◽  
Haiyan Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Colony Formation ◽  
Xenograft Model ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Western Blot Assay ◽  
Major Barrier

Background: Chemoresistance is a major barrier to the treatment of human cancers. Circular RNAs (circRNAs) are implicated in drug resistance in cancers, including gastric cancer (GC). In this study, we aimed to explore the functions of circRNA Armadillo Repeat gene deleted in Velo-Cardio-Facial syndrome (circARVCF) in cisplatin (DDP) resistance in GC.Methods: The expression of circARVCF, microRNA-1205 (miR-1205) and fibroblast growth factor receptor 1 (FGFR1) was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blot assay or immunohistochemistry (IHC) assay. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were performed to evaluate DDP resistance and cell colony formation ability. Transwell assay was conducted to assess cell migration and invasion. Flow cytometry analysis was done to analyze cell apoptosis. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were manipulated to analyze the relationships of circARVCF, miR-1205 and FGFR1. Murine xenograft model was constructed to explore DDP resistance in vivo.Results: CircARVCF level was increased in DDP-resistant GC tissues and cells. CircARVCF silencing inhibited DDP resistance, colony formation and metastasis and induced apoptosis in DDP-resistant GC cells. CircARVCF directly interacted with miR-1205 and miR-1205 inhibition reversed circARVCF silencing-mediated effect on DDP resistance in DDP-resistant GC cells. FGFR1 served as the target gene of miR-1205. MiR-1205 overexpression restrained the resistance of DDP-resistant GC cells to DDP, but FGFR1 elevation abated the effect. In addition, circARVCF knockdown repressed DDP resistance in vivo.Conclusion: CircARVCF enhanced DDP resistance in GC by elevating FGFR1 through sponging miR-1205.

scholarly journals Circ_0082182 promotes oncogenesis and metastasis of colorectal cancer in vitro and in vivo by sponging miR-411 and miR-1205 to activate the Wnt/β-catenin pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ruijie Liu ◽  
Ping Deng ◽  
Yonglian Zhang ◽  
Yonglan Wang ◽  
Cuiping Peng
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Xenograft Model ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mesenchymal Transition

Abstract Background Circular RNAs (circRNAs) are a class of endogenous single-strand RNA transcripts with crucial regulation in human cancers. The objective of this study is to investigate the role of circ_0082182 in CRC and its specific functional mechanism. Methods The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the levels of circ_0082182, microRNA-411 (miR-411) and microRNA-1205 (miR-1205). Cell proliferation was detected by Cell counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used for determining cell cycle and cell apoptosis. Cell apoptosis was also assessed by caspase3 and caspase9 activities. Cell migration and invasion were examined using scratch assay and transwell assay. The interaction between circ_0082182 and miRNA was validated by the dual-luciferase reporter and biotinylated RNA pull-down assays. Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by Western blot. Xenograft model was established for the research of circ_0082182 in vivo. Results Circ_0082182 was upregulated in CRC and could predict the poor prognosis of CRC patients. Functionally, circ_0082182 promoted CRC cell proliferation, cell cycle progression, and metastasis while inhibited apoptosis. Subsequently, circ_0082182 was shown to act as the sponges of miR-411 and miR-1205. MiR-411 and miR-1205 were identified as tumor inhibitors in CRC. Furthermore, circ_0082182 promoted the CRC progression via sponging miR-411 and miR-1205. Moreover, circ_0082182 facilitated the Wnt/β-catenin pathway and EMT process by targeting miR-411 and miR-1205. In vivo, circ_0082182 accelerated the CRC tumorigenesis and EMT process by activating the Wnt/β-catenin pathway by downregulating the expression of miR-411 or miR-1205. Conclusion This study showed that circ_0082182 functioned as an oncogene in the developing process of CRC by sponging miR-411 or miR-1205 to activate the Wnt/β-catenin pathway. Circ_0082182 might be a molecular target in the diagnosis and treatment of CRC.

scholarly journals Silencing of hsa_circ_0009035 suppresses cervicalprogression and enhances radiosensitivity through miR-889-3p-dependent regulation of HOXB7

2021 ◽  
Author(s):  
Xia Zhao ◽  
Weilei Dong ◽  
Guifang Luo ◽  
Jing Xie ◽  
Jie Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Colony Formation ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
The Impact

Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, have been identified as critical regulators in human carcinogenesis. Here, we investigated the precise actions of hsa_circ_0009035 in the progression and radioresistance of cervical cancer (CC). The levels of hsa_circ_0009035, microRNA (miR)-889-3p and homeobox B7 (HOXB7) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Ribonuclease R (RNase R) and Actinomycin D assays were used to assess the stability of hsa_circ_0009035. Cell proliferation, cell cycle progression, apoptosis, migration and invasion were gauged by the Cell Counting Kit-8 (CCK-8), flow cytometry and transwell assays, respectively. Cell colony formation and survival were determined by the colony formation assay. Targeted correlations among hsa_circ_0009035, miR-889-3p and HOXB7 were examined by the dual-luciferase reporter, RNA immunoprecipitation (RIP) or RNA pull-down assay. Animal studies were performed to evaluate the impact of hsa_circ_0009035 on tumor growth. We found that hsa_circ_0009035 was highly expressed in CC tissues and cells, and it was associated with the radioresistance of CC patients. Moreover, the silencing of hsa_circ_0009035 inhibited CC cell proliferation, migration, invasion, and enhanced apoptosis and radiosensitivity in vitro and weakened tumor growth in vivo. Mechanistically, hsa_circ_0009035 directly targeted miR-889-3p by binding to miR-889-3p, and hsa_circ_0009035 modulated HOXB7 expression through miR-889-3p. HOXB7 was a functional target of miR-889-3p in regulating CC progression and radioresistance in vitro, and hsa_circ_0009035 modulated CC progression and radioresistance in vitro by miR-889-3p. Our current study first identified hsa_circ_0009035 as an important regulation of CC progression and radioresistance at least in part through targeting the miR-889-3p/HOXB7 axis, highlighting its significance as a potential therapeutic target for CC treatment.

scholarly journals Circ_0003998 enhances doxorubicin resistance in hepatocellular carcinoma by regulating miR-218-5p/EIF5A2 pathway

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Xiaomin Li ◽  
Jiefeng He ◽  
Xiaojing Ren ◽  
Haichao Zhao ◽  
Haoliang Zhao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Translation Initiation Factor ◽  
Cell Counting ◽  
Initiation Factor ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Reaction Cell

Abstract Background The involvement of circular RNAs (circRNAs) in chemoresistance of tumors has been identified. Herein, this study aims to investigate the role and the underlying mechanism of circ_0003998 in doxorubicin (DOX) resistance in hepatocellular carcinoma (HCC). Methods The expression of circ_0003998 and microRNA (miR)-218-5p and eukaryotic translation initiation factor 5A-2 (EIF5A2) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability, migration and invasion were analyzed using cell counting kit-8, colony formation and transwell assay, respectively. The levels of matrix metallopeptidase 9 (MMP-9), E-cadherin, Vimentin, N-cadherin and EIF5A2 protein were detected using western blot. The interaction between miR-218-5p and circ_0003998 or EIF5A2 was confirmed by dual-luciferase reporter assay. In vivo experiments were performed using murine xenograft models. Results Circ_0003998 was elevated in HCC tissues, DOX-resistant tissues and cells, and circ_0003998 knockdown promoted DOX-sensitivity in HCC by inhibiting resistant cell viability, migration, invasion and EMT in vitro and enhanced DOX cytotoxicity in vivo. Bioinformatics analysis revealed circ_0003998 inhibited miR-218-5p expression, which was clarified to be a target of circ_0003998, and circ_0003998 knockdown sensitized HCC cell to DOX by sponging miR-218-5p. EIF5A2 was a target of miR-218-5p, and miR-218-5p mitigated DOX resistance in HCC cells through modulating EIF5A2 expression. Additionally, circ_0003998 served as a competing endogenous RNA for miR-218-5p to regulate EIF5A2 expression. Conclusion Circ_0003998 knockdown sensitized HCC cell to DOX by regulating miR-218-5p/EIF5A2 axis, indicating new markers of poor response to DOX and potential therapeutic strategies for the chemotherapy of HCC.

scholarly journals Circular RNA circ_0081001 knockdown enhances methotrexate sensitivity in osteosarcoma cells by regulating miR-494-3p/TGM2 axis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wei Wei ◽  
Liefeng Ji ◽  
Wanli Duan ◽  
Jiang Zhu
Keyword(s):  
Cell Viability ◽  
Xenograft Model ◽  
Transglutaminase 2 ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas

Abstract Background Circular RNAs (circRNAs) have been shown to participate in the chemoresistance and tumorigenesis of multiple cancers. The purpose of this research was to investigate the function of circ_0081001 in methotrexate (MTX) resistance of osteosarcoma (OS) and its potential molecular mechanism. Methods The expression of circ_0081001, cytochrome P450 family 51 subfamily A member 1 (CYP51A1), and miR-494-3p was detected by qRT-PCR. Cell viability, apoptosis, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay, respectively. Western blot (WB) assay was used to measure the protein levels of cleaved-caspase3 (cleaved-casp3), E-cadherin, N-cadherin, and transglutaminase-2 (TGM2). The interaction between miR-494-3p and circ_0081001 or TGM2 was predicted by bioinformatics analysis and verified using the dual-luciferase reporter assay. The mice xenograft model was established to investigate the roles of circ_0081001 in MTX resistance of OS in vivo. Results Circ_0081001 and TGM2 were upregulated, and miR-494-3p was downregulated in MTX-resistant OS tissues and cells. Moreover, circ_0081001 interference enhanced cell sensitivity to MTX through promoting apoptosis and inhibiting cell viability and metastasis in vitro. Furthermore, circ_0081001 was identified as a molecular sponge of miR-494-3p to upregulate TGM2 level. In addition, circ_0081001 knockdown inhibited MTX resistance via upregulating miR-494-3p and downregulating TGM2. Besides, circ_0081001 downregulation improved MTX sensitivity of OS in vivo. Conclusion Knockdown of circ_0081001 enhanced MTX sensitivity of OS cells through downregulating TGM2 by sponging miR-494-3p, elucidating a novel regulatory mechanism for chemoresistance of OS and providing a potential circRNA-targeted therapy for OS.

scholarly journals Circ-RNF111 aggravates the malignancy of gastric cancer through miR-876-3p-dependent regulation of KLF12

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Guoxian Wu ◽  
Aimin Zhang ◽  
Yinglin Yang ◽  
Dongping Wu
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Viability ◽  
Colony Formation ◽  
Xenograft Model ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Aberrant Expression

Abstract Background The aberrant expression of circular RNAs (circRNAs) plays vital roles in the advancement of human cancers, including gastric cancer (GC). In this study, the functions of circRNA ring finger protein 111 (circ-RNF111) in GC were investigated. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed for the levels of circ-RNF111, microRNA-876-3p (miR-876-3p) and krueppel-like factor 12 (KLF12) mRNA. RNase R assay was conducted for the feature of circ-RNF111. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, wound-healing assay, and transwell assay were applied for cell viability, colony formation, migration, and invasion, respectively. Flow cytometry analysis was used to analyze cell apoptosis and cell cycle process. The glycolysis level was examined using specific commercial kits. Western blot assay was carried out to measure the protein levels of hexokinase 2 (HK-2) and KLF12. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the combination between miR-876-3p and circ-RNF111 or KLF12. Murine xenograft model was constructed for the role of circ-RNF111 in vivo. Immunohistochemistry (IHC) was used for KLF12 level. Results Circ-RNF111 was higher expressed in GC tissues and cells than normal tissues and cells. Silencing of circ-RNF111 restrained cell viability, colony formation, migration, invasion, cell cycle process and glycolysis and induced apoptosis in GC cells in vitro. Circ-RNF111 positively regulated KLF12 expression via absorbing miR-876-3p. MiR-876-3p downregulation reversed the impacts of circ-RNF111 silencing on GC cell malignant phenotypes. MiR-876-3p overexpression repressed GC cell growth, metastasis and glycolysis, inhibited apoptosis and arrested cell cycle, while KLF12 elevation weakened the effects. Besides, circ-RNF111 knockdown inhibited tumor growth in vivo. Conclusion Circ-RNF111 knockdown relieved the development of GC by regulating miR-876-3p/KLF12 axis.

scholarly journals CircRFX3 contributes to glioma progression through the circRFX3-miR-1179/miR-1229-VASP axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hongli Li ◽  
Yiwei Zhang ◽  
Huiqin Song ◽  
Li Li
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Xenograft Model ◽  
Tumor Promoter ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Western Blot Assay

Abstract Background Circular RNAs (circRNAs) are implicated in the carcinogenesis of human cancers. However, the functional roles of circRFX3 in glioma are not elucidated. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed for the levels of circRFX3, RFX3, miR-1179, miR-1229 and vasodilator stimulated phosphoprotein (VASP). Actinomycin D assay and RNase R assay were employed to analyze the characteristics of circRFX3. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were conducted for cell proliferation. Transwell assay was used for cell migration and invasion. Flow cytometry analysis was adopted for cell apoptosis. RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to analyze the interaction between miR-1179/miR-1229 and circRFX3 or VASP. Western blot assay was conducted for VASP protein level. Murine xenograft model assay was used to investigate the role of circRFX3 in vivo. Results CircRFX3 level was increased in glioma tissues and cells. Knockdown of circRFX3 suppressed glioma cell proliferation, migration and invasion and promoted apoptosis in vitro and repressed tumorigenesis of glioma in vivo. MiR-1179 and miR-1229 were identified to be the targets of circRFX3. MiR-1179 or miR-1229 inhibition reversed the impacts of circRFX3 knockdown on glioma cell malignant behaviors. Additionally, VASP was demonstrated to be the target gene of miR-1179 and miR-1229, and VASP overexpression abolished the effect of circRFX3 knockdown on glioma cell progression. Conclusion CircRFX3 served as a tumor promoter in glioma via modulating miR-1179/miR-1229-VASP axis, which might provide a novel target for glioma therapy.

scholarly journals Circ-BANP Contributes to Cell Carcinogenesis and Aerobic Glycolysis by Regulating MAPK1 Through miR-874-3p in Colorectal Cancer

2021 ◽  
Author(s):  
Yunxin Zhang ◽  
Kexin Shen ◽  
Hanyi Zha ◽  
Wentao Zhang ◽  
Haishan Zhang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Xenograft Model ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Luciferase Reporter

Abstract BackgroundCircular RNA-BTG3 associated nuclear protein (circ-BANP) was identifified to involve in cell proliferation of colorectal cancer (CRC). The aerobic glycolysis is a key metabolism mediating cancer progression. However, the role of circ-BANP on aerobic glycolysis in CRC remains unknown. MethodsThe expression of circ-BANP, microRNA (miR)-874-3p, and mitogen-activated protein kinase 1 (MAPK1) mNRA was detected using quantitative real-time polymerase chain reaction. Cell viability and invasion were measured by cell counting kit-8 assay or transwell assay. Glucose consumption and lactate production were assessed by a glucose and lactate assay kit. XF Extracellular Flux Analyzer was used to determine extracellular acidifification rate (ECAR). Western blot was used to analyze the levels of hexokinase-2 (HK2), pyruvate kinase M2 (PKM2), MAPK1, proliferating cell nuclear antigen (PCNA), Cyclin D1, N-cadherin, E-cadherin, hypoxia inducible factor-1α (HIF-1α), glucose transport protein 1(GLUT1), and c-Myc. The interaction between miR-874-3p and circ-BANP or MAPK1 was confifirmed by dual luciferase reporter assay. In vivo experiments were conducted through the murine xenograft model. ResultsCirc-BANP was up-regulated in CRC tissues and cell lines. Circ-BANP knockdown suppressed CRC cell proliferation, invasion and aerobic glycolysis in vitro as well as inhibited tumor growth in vivo. Circ-BANP was a sponge of miR-874-3p and performed anti-tumor effffects by binding to miR-874-3p in CRC cells. Subsequently, we confifirmed MAPK1 was a target of miR-874-3p and circ-BANP indirectly regulated MAPK1 expression by sponging miR-874-3p. After that, we found MAPK1 overexpression partially reversed circ-BANP deletion-mediated inhibition on cell carcinogenesis and aerobic glycolysis in CRC. ConclusionCirc-BANP accelerated cell carcinogenesis and aerobic glycolysis by regulating MAPK1 through miR- 874-3p in CRC, suggesting a promising therapeutic strategy for CRC treatment.

scholarly journals CircSEC24A promotes colorectal cancer progression by regulating miR-488-3p/TMEM106B axis

2020 ◽  
Author(s):  
Gaowu Hu ◽  
Wei Peng ◽  
Yongqing Cao
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Transmembrane Protein ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Cell Progression

Abstract Background: Currently, more and more circular RNAs (circRNAs) have been identified to exert their functions in tumor progression, including colorectal cancer (CRC). However, the role of circSEC24A (circ_0003528) in CRC remains unknown.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the levels of circSEC24A, SEC24A and microRNA-488-3p (miR-488-3p). The characterization of circSEC24A was investigated by Actinomycin D and RNase R digestion assays. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to assess cell proliferation. Flow cytometry analysis was adopted for cell apoptosis and cell cycle process. Transwell assay was employed to evaluate cell migration and invasion. Western blot assay was performed to determine protein levels. Dual-luciferase reporter assay was utilized to explore the relationship between miR-488-3p and circSEC24A or transmembrane protein 106B (TMEM106B). Murine xenograft model was constructed to explore the effect of circSEC24A in vivo .Results: CircSEC24A level was increased in CRC tissues and cells. CircSEC24A deficiency impeded cell proliferation, cell cycle process, migration and invasion and induced apoptosis in CRC cells in vitro and blocked tumorigenesis in vivo . MiR-488-3p was a target of circSEC24A and miR-488-3p was downregulated in CRC tissues and cells. The inhibitory effect of circSEC24A silencing on CRC cell progression was restored by miR-488-3p inhibition. Moreover, TMEM106B could be negatively regulated by miR-488-3p via acting as a downstream gene of miR-488-3p. MiR-488-3p overexpression decelerated CRC cell progression by targeting TMEM106B.Conclusion: CircSEC24A facilitated CRC progression by regulating miR-488-3p/TMEM106B axis, which might provide a promising treatment approach for CRC.

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