scholarly journals circ_0075943 Dominates the miR-141-3p/AK2 Network to Support the Development of Breast Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Haixia Wang ◽  
Xuechun Zhao ◽  
Hui Wang
Keyword(s):  
Real Time ◽  
Cell Function ◽  
Animal Experiments ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Luciferase Reporter Gene ◽  
Rna Immunoprecipitation ◽  
Formation Method ◽  
Pcr Technology

Background. Breast cancer (BC) progression is related to the disorder of circular RNAs (circRNAs). This study aims to characterize the role of circ_0075943 in BC. Methods. Real-time fluorescent quantitative PCR (real-time PCR) technology was implemented to investigate circ_0075943, AK2 mRNA, and microRNA-141-3p levels. MTT, colony formation method, Transwell, and flow cytometry technique were adopted to investigate cell function. The connection between miR-141-3p and circ_0075943 or AK2 was confirmed by the dual-luciferase reporter gene or RNA immunoprecipitation (RIP). The influence on circ_0075943 in vivo was confirmed by animal experiments. Results. circ_0075943 was augmented in BC cell lines and tumor specimens. Dwindling of circ_0075943 could dramatically suppress the phenotype of BC cells and induce apoptosis. MiR-141-3p is a target of circ_0075943, and its repression largely reverses the influence of knocking down circ_0075943 on cell behavior. Moreover, AK2, as a target of miR-141-3p, is augmented in BC cells and specimens. AK2 overexpression could restore the phenotype of BC cells blocked by miR-141-3p redevelopment. Moreover, knocking down circ_0075943 could suppress the growth of tumors in vivo. Conclusion. The abnormal regulation of circ_0075943 participates in part of the expansion of BC by dominating the miR-141-3p/AK2 regulatory network.

Circ_0007031 enhances tumor progression and promotes 5-fluorouracil resistance in colorectal cancer through regulating miR-133b/ABCC5 axis

2020 ◽  
Vol 29 (4) ◽  
pp. 531-542
Author(s):  
Xiaowen He ◽  
Jun Ma ◽  
Mingming Zhang ◽  
Jianhua Cui ◽  
Hao Yang
Keyword(s):  
Colorectal Cancer ◽  
Colony Formation ◽  
Human Cancer ◽  
Animal Experiments ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Cell Progression ◽  
Rna Immunoprecipitation

Colorectal cancer (CRC) remains one of the most commonly diagnosed malignancies worldwide. Circular RNAs (circRNAs) are being found to play crucial roles in human cancer, including CRC. The purpose of this study was to explore the function and mechanism of circ_0007031 on CRC progression and 5-fluorouracil (5-FU) resistance. The levels of circ_0007031, ATP-binding cassette subfamily C member 5 (ABCC5) and miR-133b were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell survival and proliferation were detected by the 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Cell colony formation was evaluated using a standard colony formation assay. Transwell assays were performed to determine cell migration and invasion. Targeted correlations among circ_0007031, miR-133b and ABCC5 were verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pulldown assays. Animal experiments were performed to observe the role of circ_0007031 in vivo. Our data indicated that circ_0007031 up-regulation was associated with CRC resistance to 5-FU. Circ_0007031 knockdown repressed CRC cell proliferation, migration and invasion and enhanced 5-FU sensitivity. Circ_0007031 directly interacted with miR-133b. Moreover, circ_0007031 knockdown regulated CRC cell progression and 5-FU sensitivity by miR-133b. ABCC5 was a direct target of miR-133b, and circ_0007031 mediated ABCC5 expression via acting as a miR-133b sponge. Furthermore, miR-133b overexpression regulated CRC cell progression and sensitivity to 5-FU by down-regulating ABCC5. Additionally, circ_0007031 knockdown suppressed tumor growth in vivo. Our current work had led to the identification of circ_0007031 knockdown that repressed CRC cell malignant progression and enhanced 5-FU sensitivity via regulating ABCC5 expression by sponging miR-133b.

scholarly journals Long noncoding RNA SNHG14 promotes hepatocellular carcinoma progression by regulating miR-876-5p/SSR2 axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zhibin Liao ◽  
Hongwei Zhang ◽  
Chen Su ◽  
Furong Liu ◽  
Yachong Liu ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Animal Experiments ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Downstream Target ◽  
Protein Levels ◽  
Elevated Expression ◽  
Rna Immunoprecipitation

Abstract Background Aberrant expressions of long noncoding RNAs (lncRNAs) have been demonstrated to be related to the progress of HCC. The mechanisms that SNHG14 has participated in the development of HCC are obscure. Methods Quantitative real-time PCR (qRT-PCR) was used to measure the lncRNA, microRNA and mRNA expression level. Cell migration, invasion and proliferation ability were evaluated by transwell and CCK8 assays. The ceRNA regulatory mechanism of SNHG14 was evaluated by RNA immunoprecipitation (RIP) and dual luciferase reporter assay. Tumorigenesis mouse model was used to explore the roles of miR-876-5p in vivo. The protein levels of SSR2 were measured by western blot assay. Results In this study, we demonstrated that SNHG14 was highly expressed in HCC tissues, meanwhile, the elevated expression of SNHG14 predicted poor prognosis in patients with HCC. SNHG14 promoted proliferation and metastasis of HCC cells. We further revealed that SNHG14 functioned as a competing endogenous RNA (ceRNA) for miR-876-5p and that SSR2 was a downstream target of miR-876-5p in HCC. Transwell, CCK8 and animal experiments exhibited miR-876-5p inhibited HCC progression in vitro and in vivo. By conducting rescue experiments, we found the overexpression of SSR2 or knocking down the level of miR-876-5p could reverse the suppressive roles of SNHG14 depletion in HCC. Conclusion SNHG14 promotes HCC progress by acting as a sponge of miR-876-5p to regulate the expression of SSR2 in HCC.

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

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.

CircRNA_0092516 regulates chondrocyte proliferation and apoptosis in osteoarthritis through the miR-337-3p/PTEN axis

2020 ◽  
Author(s):  
Zhihui Huang ◽  
Wenming Ma ◽  
Jinhuai Xiao ◽  
Xiaoyu Dai ◽  
Weiqi Ling
Keyword(s):  
Cell Apoptosis ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Mechanism Analysis ◽  
Potential Mechanism ◽  
Luciferase Reporter Gene ◽  
Chondrocyte Proliferation ◽  
In Vivo Experiments

Abstract The dysregulation of circular RNAs (circRNAs) has been identified in various human diseases. Here, we probed into the potential mechanism of circRNA_0092516 in osteoarthritis (OA). The expression of circRNA_0092516 was tested by quantitative real-time PCR. MTT, flow cytometry and western blot were applied to confirm the functions of circRNA_0092516 in vitro. Besides, RNA pull-down and dual-luciferase reporter gene experiments were applied to probe into the mechanism. circRNA_0092516 was raised in the tissues of OA patients and chondrocytes stimulated by IL-1β. The potential mechanism analysis expounded that circRNA_0092516 bound to miR-337-3p, and the interference with circRNA_0092516 boosted chondrocyte proliferation and restrained cell apoptosis through the miR-337-3p/phosphatase and tensin homolog (PTEN) axis, thereby improving OA. In-vivo experiments expounded that circRNA_0092516 regulated cartilage production through miR-337-3p. Overall, our data expounded that the interference with circRNA_0092516 boosted chondrocyte proliferation and restrained cell apoptosis through the miR-337-3p/PTEN axis, eventually slowed down the progress of OA.

scholarly journals Circular RNA circASPM Promotes the Progression of Glioblastoma by Acting as a Competing Endogenous RNA to Regulate miR-130b–3p/E2F1 Axis

2020 ◽  
Author(s):  
Dianqi Hou ◽  
Zhenlin Wang ◽  
Haimeng Li ◽  
Juan Liu ◽  
Yaohua Liu ◽  
...  
Keyword(s):  
Western Blotting ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Primary Malignancy ◽  
Rna Immunoprecipitation ◽  
Western Blotting Assay

Abstract background: Glioblastoma Multiform (GBM) is the primary malignancy with the highest incidence and worst prognosis in the adult CNS. Circular RNAs (circRNAs) are a novel and widely diverse class of endogenous non-coding RNAs that can promote or inhibit gliomagenesis. Our study aimed to explore the role of circASPM in GBM and its molecular mechanism.Methods: Levels of circASPM, miR-130b-3p and E2F1 were determined by quantitative real-time PCR (qRT-PCR) or western blotting assay. MTS, Edu, neurospheres formation and extreme limiting dilution assays were used to detect the tumorigenesis and proliferation of GSCs in vitro. The interactions between miR-130b-3p and circASPM or E2F1 was demonstrated via qPCR, western blotting, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft experiments was used to analyze tumor growth in vivo.Results: CircASPM was overexpressed in GBM and could promote the tumorigenesis and proliferation of GSCs both in vitro and in vivo. Mechanistically, circASPM up-regulated the expression of E2F1 in GSCs via miR-130b-3p sponging. We furtherly demonstrated that circAPSM could promote the GSCs proliferation via E2F1 up-regulating. Therefore, our study identified a novel circRNA and its possible mechanism in the development and tumorigenesis of GBM.Conclusions: CircASPM can promote GBM progression via regulating miR-130b-3p/E2F1 axis, suggesting that circAPSM could provide an effective biomarker for GBM diagnosis and prognostic evaluation and possibly being used for molecular targeted therapy.

scholarly journals CircKEAP1 serves as a ceRNA to suppress lung adenocarcinoma progression by activating KEAP1 signal pathway

2020 ◽  
Author(s):  
Yanbo Wang ◽  
Fenghai Ren ◽  
Dawei Sun ◽  
Jing Liu ◽  
BenKun Liu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Expression Profiles ◽  
Signal Pathway ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Tumor Tissues ◽  
Rna Immunoprecipitation

Abstract BackgroundCircular RNAs (circRNAs) are widely expressed noncoding RNAs, and plays a key role in the biological function of competitive endogenous RNA (ceRNA) network in various human diseases, especially in cancer. However, the regulatory roles of circRNAs in lung adenocarcinoma (LUAD) remains largely unknown. MethodsThe expression profiles of circRNAs in LUAD tissues and adjacent non-tumor tissues were analyzed by Agilent Arraystar Human CircRNA microarray. The level and prognostic values of circKEAP1 in tissues and cancer cell lines were determined by quantitative real-time PCR. Then, the effects of circKEAP1 on tumor growth were investigated by functional experiments in vitro and in vivo. Mechanistically, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between circKEAP1 and miR-141-3p in LUAD.ResultsWe found circKEAP1 was significantly downregulated in LUAD tissues, and repressed tumor growth both in vitro and in vivo. Mechanistically, circKEAP1 competitively binds to miR-141-3p and relive miR-141-3p repression for its target gene KEAP1, which activated the KEAP1/NRF2 signal pathway, and finally suppress the cell proliferation.ConclusionsOur findings suggest that circKEAP1 inhibits LUAD progression through circKEAP1/miR-141-3p/KEAP1 axis and it may serve as a new target for treatment of LUAD patients.

scholarly journals CircCRIM1 Promotes Hepatocellular Carcinoma Proliferation and Angiogenesis by Sponging miR-378a-3p and Regulating SKP2 Expression

2021 ◽  
Vol 9 ◽  
Author(s):  
Yang Ji ◽  
Shikun Yang ◽  
Xueqi Yan ◽  
Li Zhu ◽  
Wenjie Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Clinicopathologic Characteristics ◽  
Huh7 Cells ◽  
Rna Immunoprecipitation ◽  
Reporter Assays

Mounting evidence has demonstrated that circular RNAs have an important function in tumorigenesis and cancer evolvement. CircCRIM1 has been shown to be a poor prognostic element in multiple human malignancies. However, the clinical significance and mechanism of circCRIM1 in hepatocellular carcinoma (HCC) is still unclear. The present study confirmed the expression level of circCRIM1 using quantitative real-time PCR. In addition, circCRIM1 siRNA and overexpression vectors were used for transfection into LM3 or Huh7 cells to down- or up-regulate the expression of circCRIM1. In vitro and in vivo experiments were performed to explore the function of circCRIM1 in HCC. RNA pull-down, RNA immunoprecipitation, fluorescent in situ hybridization, and luciferase reporter assays were conducted to confirm the relationship between miR-378a-3p and circCRIM1 or S-phase kinase-associated protein 2 (SKP2) in HCC. Then, circCRIM1 was up-regulated in HCC and its expression level was significantly associated with poor prognosis and clinicopathologic characteristics. CircCRIM1 enhanced the proliferation and angiogenesis of HCC cells in vitro and promoted xenograft growth in vivo. Moreover, circCRIM1 upregulated the expression of SKP2 by functioning as a sponge for miR-378a-3p. These findings suggest that circCRIM1 boosts the HCC progression via the miR-378-3p/SKP2 axis and may act as a crucial epigenetic therapeutic molecule target in HCC.

scholarly journals CircWHSC1 promotes ovarian cancer progression by regulating MUC1 and hTERT through sponging miR-145 and miR-1182

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Zhi-Hong Zong ◽  
Yu-Ping Du ◽  
Xue Guan ◽  
Shuo Chen ◽  
Yang Zhao
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Nude Mice ◽  
Cell Apoptosis ◽  
Cell Function ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Cancer Tissues

Abstract Background Circular RNAs are key regulators in human cancers, however, there is a lack of studies on circRNAs’ specific functions in ovarian cancer. Methods Our study used qRT-PCR to detect the differentially expressed circRNAs between normal ovaries and ovarian cancer tissues. Cell function experiments were performed to verify the role of overexpression and silence of circWHSC1, including MTT assay, cell apoptosis assay, wound healing and Matrigel-coated Transwell assay. In vivo tumorigenesis model was constructed by subcutaneous injection in nude mice. Bioinformatics analysis predicted the possible binding sites of circWHSC1 with miRNAs, and confirmed with dual-luciferase reporter assay and RNA pull-down assay. The exosomes were extracted with ultracentrifugation. HE staining was also used to detect morphology of nude mice peritoneum. Results We found that circWHSC1 was up-regulated in ovarian cancer tissues, and circWHSC1 expression was higher in moderate & poor differentiation ovarian cancer tissues than in well differentiation ovarian cancer tissues. Overexpression of circWHSC1 increased cell proliferation, migration and invasion, and inhibited cell apoptosis. Silence of circWHSC1 exerted the opposite effects. Additionally, circWHSC1 could sponge miR-145 and miR-1182 and up-regulate the expression of downstream targets MUC1 and hTERT. Exosomal circWHSC1 can be transferred to peritoneal mesothelial cells and promotes peritoneal dissemination. Conclusions Our study demonstrates the highly expressed circWHSC1 in ovarian cancer promotes tumorigenesis by sponging miR-145 and miR-1182, and its exosome forms induce tumor metastasis through acting on peritoneal mesothelium.

scholarly journals Circular RNA circSIPA1L1 Contributes to Osteosarcoma Progression via the miR-411-5p/RAB9A Axis

2020 ◽  
Author(s):  
Yining Xu ◽  
Teng Yao ◽  
Haonan Ni ◽  
Rujie Zheng ◽  
Kangmao Huang ◽  
...  
Keyword(s):  
Real Time ◽  
Cell Lines ◽  
Mrna Level ◽  
Circular Rna ◽  
Tumor Promoter ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Driver Gene

Abstract BackgroundRecently, various studies have identified circular RNAs (circRNAs) to play a significant role in tumorigenesis, thereby showing potential as novel tumor biomarkers. circSIPA1L1 is a new-found circular RNA formed by back-splicing of SIPA1L1 and is found increased in osteosarcoma (OS). Nevertheless, the specific functions of circSIPA1L1 in OS remain unknown. MethodsIn the present study, circSIPA1L1 was obtained from a previously reported circRNA microarray (GSE96964) in the GEO database. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA level of circSIPA1L1 in OS cell lines and tissue samples. Bioinformatics analysis, luciferase reporter assays, real-time PCR, RNA pull-down assays and RNA immunoprecipitation (RIP) were employed to verify the binding of circSIPA1L1 with miR-411-5p. Xenograft tumor models were established to identify the role of circSIPA1L1 in vivo. A series of in-vitro experiments, such as western blotting , colony formation, transwell assays and anoikis assay were employed to confirm the relationship across circSIPA1L1, miR-411-5p, and RAB9A. ResultsOur study confirmed circSIPA1L1 to be upregulated in both human OS samples and OS cell lines. Mechanistically, circSIPA1L1 could serve as a miR-411-5p molecular sponge to increase RAB9A expression, which was confirmed to be a tumor promoter mediating carcinogenesis. Silencing of circSIPA1L1 attenuated the vitality, invasion, migration and proliferation of OS cell lines both in vivo and in vitro. miR-411-5p inhibition or RAB9A overexpression reversed the anti-tumor effects caused by circSIPA1L1 knockdown. ConclusionBriefly, circSIPA1L1 acts as a driver gene in OS and could initiate OS tumorigenesis via the miR-411-5p/RAB9A axis, which might become a potential therapeutic biomarker for OS treatment.

scholarly journals Circular RNA hsa_circ_0000073 Enhances Osteosarcoma Cells Malignant Behavior by Sponging miR-1252-5p and Modulating CCNE2 and MDM2

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhijing Ren ◽  
Qinqin Yang ◽  
Jiajia Guo ◽  
Haifeng Huang ◽  
Bo Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Malignant Tumor ◽  
Cell Function ◽  
Circular Rna ◽  
Tumor Promoter ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Novel Target

Objective: An increasing number of studies have demonstrated that circular RNAs (circRNAs) are involved in tumor progression. However, the role of hsa_circ_0000073 in osteosarcoma (OS) is still not fully elucidated.Methods: Quantitative reverse transcription-polymerase chain reaction or Western blot was used to detect the gene expression. GeneChip analysis, bioinformatics, luciferase reporter, and RNA immunoprecipitation assays were adopted to predict and verify the relationships between genes. Counting Kit-8 Assay, clone formation assay, wound-healing assay, transwell assays, cell cycle assays, and in vivo tumorigenesis were used to evaluate cell function.Results: hsa_circ_0000073 was highly expressed in OS cell lines and could promote OS progression, including proliferation, migration, invasion, and cell cycle in vitro as well as tumorigenesis in vivo. Mechanically, hsa_circ_0000073 could readily downregulate the expression of CCNE2 and MDM2 through miR-1252-5p. Rescue experiments validated miR-1252-5p mimics, or CCNE2/MDM2 short hairpin RNA could reverse the hsa_circ_0000073 overexpressing-induced impairment of malignant tumor behavior.Conclusion: hsa_circ_0000073 functions as a tumor promoter in OS to increase malignant tumor behavior through sponging miR-1252-5p and regulating CCNE2 and MDM2 expression, which could be a novel target for OS therapy.

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