Circular RNA circRPPH1 promotes breast cancer progression via circRPPH1-miR-512-5p-STAT1 axis.
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ABSTRACT:
SUBMITTER: Huang Y
PROVIDER: S-EPMC8648777 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Circular RNAs (circRNAs), which are considered to be important functional regulators in cancer, have provided a new perspective regarding our understanding of tumor biology, including that of breast cancer. To investigate the regulatory effect of circRPPH1 on cellular behaviors of breast cancer and the potential mechanism, the expression of circRPPH1 and miR-556-5p in breast cancer tissues and cell lines were examined by quantitative RT-PCR. The regulatory effects of the circRPPH1/miR-556-5p/YAP1 axis on cellular behaviors of breast cancer cells were evaluated through functional experiments in vitro and tumor growth in vivo. The relationship between circRPPH1 and miR-556-5p/YAP1 was assessed using dual-luciferase reporter and RNA immunoprecipitation assays. PCR results showed that circRPPH1 levels were significantly upregulated in tumor tissues and breast cancer cells. Functionally, circRPPH1 promoted the proliferation, migration, invasion, and angiogenesis of breast cancer cell lines and tumor growth in vivo. Regarding the mechanism, dual-luciferase reporter and RNA immunoprecipitation assays showed that circRPPH1 was capable of sponging miR-556-5p to increase expression of the oncogene YAP1. Our data reveal that circRPPH1 plays a vital regulatory role in breast cancer via the miR-556-5p/YAP1 axis and may serve as a promising therapeutic target for breast cancer treatment.
| S-EPMC7653573 | biostudies-literature
Project description:BackgroundAccumulating evidences have shown that circular RNAs (circRNAs) play important roles in regulating the pathogenesis of cancer. However, the role of circRNAs in gastric cancer (GC) remains largely unclear.MethodsIn this study, we identified a novel upregulated circRNA, hsa_circ_0001829, in chemically induced malignant transformed human gastric epithelial cells using RNA-seq. Subsequent qRT-PCR and ISH assays were performed to detect the expression level of hsa_circ_0001829 in GC cell lines and tissues. Functional roles of hsa_circ_0001829 in GC were then explored by loss- and gain-of- function assays. Bioinformatic prediction and luciferase assay were used to investigate potential mechanisms of hsa_circ_0001829. Finally, the mice xenograft and metastasis models were constructed to assess the function of hsa_circ_0001829 in vivo.ResultsWe found that hsa_circ_0001829 was significantly upregulated in GC tissues and cell lines. Loss- and gain-of- function assays showed that hsa_circ_0001829 promotes GC cells proliferation, migration and invasion, and the affected cell cycle progression and apoptosis rates may account for the effect of hsa_circ_0001829 on GC proliferation. In addition, bioinformatic prediction and luciferase assay showed that hsa_circ_0001829 acts as a molecular sponge for miR-155-5p and that SMAD2 was a target gene of miR-155-5p; moreover, hsa_circ_0001829 sponges miR-155-5p to regulate SMAD2 expression and hsa_circ_0001829 promotes GC progression through the miR-155-5p-SMAD2 pathway. Finally, suppression of hsa_circ_0001829 expression inhibited tumor growth and aggressiveness in vivo.ConclusionTaken together, our findings firstly demonstrated a novel oncogenic role of hsa_circ_0001829 in GC progression through miR-155-5p-SMAD2 axis, and our study may offer novel biomarkers and therapeutic targets for GC.
| S-EPMC7731483 | biostudies-literature
Project description:Patients with advanced prostate cancer (PCa) have poor prognosis. Circular RNAs (circRNAs) regulate biological processes in a variety of cancers, but the precise roles of circRNAs in PCa are poorly understood. Herein, we identified a novel circRNA, termed circMBOAT2 (has_circ_0007334), which was significantly overexpressed in PCa tissues and cell lines. Overexpression of circMBOAT2 was associated with high Gleason score, advanced pathological T stage, and poor prognosis. Overexpression of circMBOAT2 promoted proliferation, migration, and invasion of PCa cells in vitro, and enhanced tumorigenesis and metastasis in vivo. Mechanistically, circMBOAT2 overexpression upregulated the expression of mTOR by acting as a decoy for miR-1271-5p, resulting in the activation of the PI3K/Akt pathway, ultimately promoting the progression of PCa. Importantly, application of an inhibitor of mTOR significantly antagonized circMBOAT2-mediated PCa tumorigenesis in vivo. circMBOAT2 promotes proliferation and metastasis of PCa through miR-1271-5p/mTOR axis-mediated activation of the PI3K/Akt pathway. In summary, our findings uncover a molecular mechanism in the progression of PCa and indicate that circMBOAT2 may be a useful prognostic biomarker and therapeutic target in PCa.
| S-EPMC7377862 | biostudies-literature
Project description:BackgroundMounting evidence indicates that circular RNAs (circRNAs) participate in the occurrence and development of various diseases, including osteoarthritis (OA). However, the effects and molecular mechanism of circ_0128846 in OA have not been reported.MethodsThe expression levels of circ_0128846, microRNA-127-5p (miR-127-5p), and nicotinamide phosphoribosyltransferase (NAMPT) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was examined by flow cytometry and western blot assay. Inflammatory response and cartilage extracellular matrix (ECM) degradation were evaluated by western blot assay. The relationship between miR-127-5p and circ_0128846 or NAMPT was predicted by bioinformatics tools and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays.ResultsCirc_0128846 and NAMPT were upregulated and miR-127-5p was downregulated in OA cartilage tissues. Knockdown of circ_0128846 increased cell viability and inhibited apoptosis, inflammation and ECM degradation in OA chondrocytes, while these effects were reversed by downregulating miR-127-5p. Moreover, circ_0128846 positively regulated NAMPT expression by sponging miR-127-5p. Furthermore, miR-127-5p promoted cell viability and suppressed apoptosis, inflammation, and ECM degradation in OA chondrocytes by directly targeting NAMPT.ConclusionCirc_0128846 knockdown might inhibit the progression of OA by upregulating miR-127-5p and downregulating NAMPT, offering a new insight into the potential application of circ_0128846 in OA treatment.
| S-EPMC8112058 | biostudies-literature
Project description:Circular RNAs (circRNAs) are a group of noncoding RNAs derived from back-splicing events. CircRNA is reported to be involved in various tumor progressions, including glioma. Although there are a few reports of circular RNAs participating in gliomas, it is still unclear whether circular RNAs regulate the occurrence of gliomas. In our research, we found that the expression of circITGA7 in glioma tissues and glioma cells increased significantly. Knocking down circITGA7 can significantly inhibit the proliferation of glioma cells and reduce cell metastasis. Through analysis and dual-luciferase report assay, we found that circITGA7 acts as a sponge for miR-34a-5p targeting VEGFA in glioma. Our study showed that circITGA7 regulates the proliferation and metastasis of glioma cell lines (SW1783&U373) by regulating the miR-34a-5p/VEGFA pathway. In conclusion, our study revealed a regulatory loop for the circITGA7/miR-34a-5p/VEGFA axis to regulate glioma development.
| S-EPMC8148479 | biostudies-literature
Project description:Circular RNAs (circRNAs) are group of noncoding RNAs derived from back-splicing events. Accumulating evidence certifies the critical roles of circRNAs in human tumorigenesis. However, the role and biogenesis of circRNAs in cervical cancer are still unclear. Here, a novel identified circRNA, circSLC26A4, was found to be upregulated in cervical cancer tissue and cells. Clinically, the high expression of circSLC26A4 was related to the poor survival of cervical cancer patients. Functionally, cellular experiments indicated that circSLC26A4 knockdown repressed the proliferation, invasion, and tumor growth in vitro and in vivo. Furthermore, circSLC26A4 acted as the sponge of miR-1287-5p; moreover, miR-1287-5p targeted the 3' UTR of HOXA7 mRNA. Mechanistically, RNA binding protein (RBP) quaking (QKI) was identified to interact with the QKI response elements (QREs) in SLC26A4 gene introns, thereby promoting circSLC26A4 biogenesis. In conclusion, these findings demonstrate that circSLC26A4 facilitates cervical cancer progression through the QKI/circSLC26A4/miR-1287-5p/HOXA7 axis, which might bring novel therapeutic strategies for cervical cancer.
| S-EPMC6940609 | biostudies-literature
Project description:BACKGROUND:Accumulating evidence suggests that circular RNAs (circRNAs) are important participants in cancer progression. However, the biological processes and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear. METHOD:CircRNAs were verified by Sanger sequencing. Colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), and Transwell assays were performed to investigate the effect of circBFAR on the proliferation, invasion, and migration of PDAC cells in vitro. RNA pull-down assays were conducted to verify the binding of circBFAR with microRNA miR-34b-5p. RESULTS:In the present study, we identified a novel circRNA (termed as circBFAR, hsa_circ_0009065) that was upregulated in a 208-case cohort of patients with PDAC. The ectopic expression of circBFAR correlated positively with the tumor-node-metastasis (TNM) stage and was related to poorer prognosis of patients with PDAC. Moreover, circBFAR knockdown dramatically inhibited the proliferation and motility of PDAC cells in vitro and their tumor-promoting and metastasis properties in in vivo models. Mechanistically, circBFAR upregulated mesenchymal-epithelial transition factor (MET) expression via sponging miR-34b-5p. Additionally, circBFAR overexpression increased the expression of MET and activated downstream phosphorylation of Akt (Ser 473) and further activated the MET/PI3K/Akt signaling pathway, which ultimately promoted the progression of PDAC cells. Importantly, application of MET inhibitors could significantly attenuate circBFAR-mediated tumorigenesis in vivo. CONCLUSIONS:Our findings showed that circBFAR plays an important role in the proliferation and metastasis of PDAC, which might be explored as a potential prognostic marker and therapeutic target for PDAC.
| S-EPMC7201986 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied.MethodsBioinformatic analysis and high-throughput RNA sequencing tools were employed to identify differentially expressed circRNAs between OS and adjacent noncancerous tissues. The expression level of circ_001422 in clinical specimens and cell lines was measured using qRT-PCR. The association of circ_001422 expression with the clinicopathologic features of 55 recruited patients with OS was analyzed. Loss- and gain-of-function experiments were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescence in situ hybridization, bioinformatics database analysis, RNA pulldown assays, dual-luciferase reporter assays, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNA regulatory network controlled by circ_001422.ResultsWe characterized a novel and abundant circRNA, circ_001422, that promoted OS progression. Circ_001422 expression was dramatically increased in OS cell lines and tissues compared with noncancerous samples. Higher circ_001422 expression correlated with more advanced clinical stage, larger tumor size, higher incidence of distant metastases and poorer overall survival in OS patients. Circ_001422 knockdown markedly repressed the proliferation and metastasis and promoted the apoptosis of OS cells in vivo and in vitro, whereas circ_001422 overexpression exerted the opposite effects. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated FGF2 expression while also initiating PI3K/Akt signaling. These events enhanced the malignant characteristics of OS cells.ConclusionsCirc_001422 accelerates OS tumorigenesis and metastasis by modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 can be therapeutically targeted to treat OS.
| S-EPMC8283840 | biostudies-literature
Project description:Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p-SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p-SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.
| S-EPMC8222372 | biostudies-literature
Project description:Breast cancer (BC) is the leading cause of cancer deaths in women worldwide. Circular RNA circ_SETD2 (circ_SETD2), also termed as hsa_circ_0065173, is reported to be abnormally expressed in BC. Nevertheless, the role and mechanism of circ_SETD2 in BC are unclear. Expression of circ_SETD2, miR-155-5p, and SCUBE2 mRNA was evaluated by quantitative real-time polymerase chain reaction. Cell cycle progression, proliferation, apoptosis, migration, and invasion were determined by flow cytometry, MTT, and transwell assays. The relationship between circ_SETD2 or SCUBE2 and miR-155-5p was verified through a dual-luciferase reporter assay. The role of circ_SETD2 in BC in vivo was confirmed by a xenograft assay. circ_SETD2 and SCUBE2 were downregulated, while miR-155-5p was upregulated in BC tissues and cells. Both circ_SETD2 and SCUBE2 elevation arrested cell cycle progression, inhibited cell proliferation, migration, and invasion, and accelerated cell apoptosis in BC cells. Moreover, circ_SETD2 upregulation repressed BC growth in vivo. Importantly, circ_SETD2 modulated SCUBE2 expression through competitively binding to miR-155-5p in BC cells. Also, the inhibitory impacts of circ_SETD2 enhancement on the malignant behavior of BC cells were restored by miR-155-5p overexpression. Besides, SCUBE2 silencing abolished miR-155-5p downregulation mediated effects on the malignant behavior of BC cells. Therefore, circ_SETD2 curbed BC progression via upregulating SCUBE2 via binding to miR-155-5p.
| S-EPMC7712504 | biostudies-literature