Circular RNA HSDL2 promotes breast cancer progression via miR-7978 ZNF704 axis and regulating hippo signaling pathway
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ABSTRACT:
SUBMITTER: Wang D
PROVIDER: S-EPMC11210124 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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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:Objective: The present study aimed to explore the association between NFIX circular RNA (circNFIX) and miR-34a-5p in glioma. Furthermore, this study investigated the influence that circNFIX has on glioma progression through the upregulation of NOTCH1 via the Notch signaling pathway by sponging miR-34a-5p. Methods: We applied five methods, CIRCexplorer2, circRNA-finder, CIRI, find-circ and MapSplice2, to screen for circRNAs with differential expression between three glioma tissue samples and three paired normal tissue samples. The GSEA software was used to confirm whether significantly different pathways were activated or inactivated in glioma tissues. The binding sites between circNFIX and miR-34a-5p were confirmed by TargetScan. QRT-PCR and western blot were used to measure the relative expression levels of circNFIX, miR-34a-5p and NOTCH and identify their correlation in glioma. RNA immunoprecipitation (RIP) validated the binding relationship between circNFIX and miR-34a-5p, while the targeted relationship between NOTCH1 and miR-34a-5p was verified by a dual luciferase reporter assay. Cell viability and mobility were examined by a CCK-8 assay and wound healing assay, and a flow cytometry assay was employed to analyze cell apoptosis. The nude mouse transplantation tumor experiment verified that si-circNFIX exerted a suppressive effect on glioma progression in vivo. Results: Twelve circRNAs were differentially expressed between the tissue types. Of those, circNFIX was the sole circRNA to be overexpressed in glioma among the five methods of finding circRNAs. In addition, the Notch signaling pathway was considerably upregulated in tumor tissues compared with the paired normal brain tissues. It was determined that circNFIX acted as a sponge of miR-34a-5p, a miRNA that targeted NOTCH1. Downregulation of circNFIX and upregulation of miR-34a-5p both inhibited cell propagation and migration. Furthermore, a miR-34a-5p inhibitor neutralized the suppressive effect of si-circNFIX on glioma cells. Si-circNFIX and miR-34a-5p mimics promoted cell apoptosis. Moreover, it was demonstrated in vivo that si-circNFIX could suppress glioma growth by regulating miR-34a-5p and NOTCH1. Conclusion: CircNFIX was markedly upregulated in glioma cells. CircNFIX could regulate NOTCH1 and the Notch signaling pathway to promote glioma progression by sponging miR-34a-5p via the Notch signaling pathway. This finding provided a deeper insight into the function of circNFIX in human glioma cancer progression.
| S-EPMC6058096 | biostudies-literature
Project description:Many studies have now demonstrated that circRNAs are aberrantly expressed in cancer and are involved in the regulation of malignant tumor progression. However, the role of circMAML3 (hsa_circ_0125392) in prostate cancer has not been reported. circMAML3 was selected from public data through screening. The circMAML3 circular characterization was performed using Sanger sequencing, agarose gel electrophoresis assay, RNase R assay and actinomycin D assay. The expression of circMAML3 in prostate cancer tissues and cells was detected by qRT-PCR. In vivo and in vitro experiments were conducted to investigate the biological functions of circMAML3 in prostate cancer. Finally, the underlying mechanism of circMAML3 was revealed by qRT-PCR, luciferase reporter assay, miRNA Pulldown, RNA immunoprecipitation, western blotting, and rescue assay. Compared to normal prostate tissue and prostate epithelial cells, circMAML3 is highly expressed in prostate cancer tissues and cell lines. CircMAML3 overexpression promotes prostate cancer proliferation and metastasis, while knockdown of circMAML3 exerts the opposite effect. Mechanistically, circMAML3 promotes prostate cancer progression by upregulating MAPK8IP2 expression through sponge miR-665. Our research indicates that circMAML3 promotes prostate cancer progression through the circMAML3/miR-665/MAPK8IP2 axis. circMAML3 and MAPK8IP2 are upregulated in prostate cancer expression and play an oncogenic role, whereas miR-665 is downregulated in prostate cancer and plays an oncogenic role. Therefore, CircMAML3 may be a potential biomarker for prostate cancer diagnosis, treatment and prognosis.
| S-EPMC10721837 | biostudies-literature
Project description:Multiple myeloma (MM) is a hematologic malignancy that results from uncontrolled plasma cell proliferation. Circular RNAs are versatile regulators that influence cancer aggression. The pathogenic mechanism of circXPO1 in MM is still unknown. In this study, the expression of circXPO1, miR-495-3p, and DNA damage-induced transcription 4 (DDIT4) was detected. Knockdown and overexpression assays were used to evaluate the effect of circXPO1 on MM. Specifically, 5-ethynyl-2'-deoxyuridine and cell counting kit-8 assay were used to investigate cell proliferation. Meanwhile, flow cytometry was adopted to detect cell apoptosis and cell cycle. Apoptosis-associated and cell cycle-related proteins were detected by Western blot. Mechanistically, biotin RNA pull-down assay and dual-luciferase assay were implemented to verify the combination among miR495-3p and circXPO1 or DDIT4. The function of circXPO1 in vivo was explored in xenograft experiments. The results showed that circXPO1 was up-regulated in both MM samples and MM cell lines and miR-495-3p was down-regulated in MM patients. Silencing circXPO1 inhibited cell proliferation, increased apoptosis rates, and caused the G1 phase arrest. Overexpression of circXPO1 yielded opposite results. In addition, RNA pull-down experiment demonstrated the interaction between circXPO1 and miR-495-3p. Silencing miR-495-3p rescued the inhibitory function caused by the knockdown of circXPO1. DDIT4 was the target of miR-495-3p. Finally, silencing circXPO1 inhibited the growth of subcutaneous tumors in vivo. In conclusion, our findings showed that circXPO1 could promote MM progression via the miR-495-3p/DDIT4 axis.
| S-EPMC10825292 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is characterized by a poor prognosis because of its insensitivity to radiation and chemotherapy. Recently, circular RNAs (circRNAs) have been found to serve important roles in hepatocellular carcinogenesis. circ‑CCT3, a novel circRNA, was screened from the differential tissue expression results of a circRNA microarray. Relative expression levels of circ‑CCT3 in specimens and cell lines were evaluated by reverse transcription‑quantitative PCR and the relationship between circ‑CCT3 and prognosis was analyzed by Kaplan‑Meier curves. The oncogenic role of circ‑CCT3 was confirmed in HCC cells through a cell counting kit‑8 (CCK‑8) assay, a colony formation assay, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, a wound‑healing assay and a Transwell assay. Bioinformatics prediction and luciferase reporter assays validated that circ‑CCT3 facilitated HCC progression through the miR‑1287‑5p/TEA domain transcription factor 1 (TEAD1) axis. TEAD1 could then directly activate patched 1 and lysyl oxidase transcription, as analyzed by chromatin immunoprecipitation and luciferase reporter assays. The present study identified a novel circRNA, circ‑CCT3, which may be used as a potential therapeutic target for HCC.
| S-EPMC7986040 | biostudies-literature
Project description:Circular RNAs are a subgroup of non-coding RNAs and generated by a mammalian genome. Herein, the expression and function of circular RNA circ-TTBK2 were investigated in human glioma cells.Fluorescence in situ hybridization and quantitative real-time PCR were conducted to profile the cell distribution and expression of circ-TTBK2 and microRNA-217 (miR-217) in glioma tissues and cells. Immunohistochemical and western blot were used to determine the expression of HNF1? and Derlin-1 in glioma tissues and cells. Stable knockdown of circ-TTBK2 or overexpression of miR-217 glioma cell lines (U87 and U251) were established to explore the function of circ-TTBK2 and miR-217 in glioma cells. Further, luciferase reports and RNA immunoprecipitation were used to investigate the correlation between circ-TTBK2 and miR-217. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate circ-TTBK2 and miR-217 function including cell proliferation, migration and invasion, and apoptosis, respectively. ChIP assays were used to ascertain the correlations between HNF1? and Derlin-1.We found that circ-TTBK2 was upregulated in glioma tissues and cell lines, while linear TTBK2 was not dysregulated in glioma tissues and cells. Enhanced expression of circ-TTBK2 promoted cell proliferation, migration, and invasion, while inhibited apoptosis. MiR-217 was downregulated in glioma tissues and cell lines. We also found that circ-TTBK2, but not linear TTBK2, acted as miR-217 sponge in a sequence-specific manner. In addition, upregulated circ-TTBK2 decreased miR-217 expression and there was a reciprocal negative feedback between them in an Argonaute2-dependent manner. Moreover, reintroduction of miR-217 significantly reversed circ-TTBK2-mediated promotion of glioma progression. HNF1? was a direct target of miR-217, and played oncogenic role in glioma cells. Remarkably, circ-TTBK2 knockdown combined with miR-217 overexpression led to tumor regression in vivo.These results demonstrated a novel role circ-TTBK2 in the glioma progression.
| S-EPMC5319142 | biostudies-other
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:Circular RNAs (circRNAs) play an important role in bladder cancer (BC). Though circRNA involvement in BC has been reported, the underlying regulatory mechanisms are unknown. In this study, we performed EdU, CCK8, colony formation and Transwell assays to establish the role of circRGNEF in BC cell migration, proliferation, and invasion. We used bioinformatics and luciferase reporter experiments to investigate the regulatory mechanism. Nude mice xenografts and live imaging were used to explore the role of circRGNEF in tumor metastasis and growth. Expression profile analysis of human circRNAs in BC revealed that circRGNEF was upregulated significantly. High circRGNEF expression was correlated with aggressive BC phenotypes. The downregulation of circRGNEF suppressed BC cell metastasis and proliferation by targeting the miR-548/KIF2C axis in vitro and in vivo; these results were verified with luciferase reporter assays. Our results show that miR-548 downregulation or KIF2C overexpression restored BC cell proliferation, migration, and invasion following silencing of circRGNEF. KIF2C overexpression reversed miR-548-induced cell invasion and migration as well as growth inhibition in vitro. In summary, the data illustrate that circRGNEF suppresses BC progression by functioning as a miR-548 sponge to enhance KIF2C expression. Therefore, circRGNEF might be a candidate BC treatment target.
| S-EPMC7202505 | biostudies-literature
Project description:Accumulated evidences suggested that circular RNAs (circRNA) played critical roles in tumorigenesis and progression. To our knowledge, no study reported the function of circular RNA DGKB (circDGKB, circRNA ID: hsa_circ_0133622) on progression of neuroblastoma (NB). Here, we showed that circDGKB was upregulated in NB tissues compared to the normal dorsal root ganglia. Moreover, the expression level of circDGKB was negatively correlated with the survival rate of NB patients. Mechanically, overexpression of circDGKB promoted the proliferation, migration, invasion, and tumorigenesis of NB cells and reduced cell apoptosis, and vice versa. In addition, qRT-PCR and/or Western blot results showed that circDGKB overexpression inhibited the expression level of miR-873 and enhanced GLI1 expression. Moreover, miR-873 functioned an opposite role to circDGKB and significantly weakened circDGKB role in promoting NB progression. Furthermore, GLI1 upregulation also rescued the miR-873 role in inhibiting NB progression. In conclusion, our work proved that circDGKB promoted NB progression via targeting miR-873/GLI1 axis in vitro and in vivo. Our study provided a new target for NB treatment and indicated that circDGKB could act as a novel diagnostic marker for NB.
| S-EPMC7390925 | biostudies-literature
Project description:Breast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3'-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.
| S-EPMC8648777 | biostudies-literature