CircRNA DDX21 acts as a prognostic factor and sponge of miR-1264/QKI axis to weaken the progression of triple-negative breast cancer.
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ABSTRACT:
SUBMITTER: Huang R
PROVIDER: S-EPMC9076009 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
Publications
CircRNA DDX21 acts as a prognostic factor and sponge of miR-1264/QKI axis to weaken the progression of triple-negative breast cancer.
Huang Renhong R Yang Zhou Z Liu Qian Q Liu Biao B Ding Xinyuan X Wang Zheng Z
Clinical and translational medicine 20220501 5
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Project description:BackgroundIn recent years, circular RNAs (circRNAs), a new star of non-coding RNA, have been emerged as vital regulators and gained much attention for involvement of initiation and progression of diverse kinds of human diseases, especially cancer. However, regulatory role, clinical significance and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) still remain largely unknown.MethodsHere, the expression profile of circRNAs in 4 pairs of TNBC tissues and adjacent non-tumor tissues was analyzed by RNA-sequencing. Quantitative real-time PCR and in situ hybridization were used to determine the level and prognostic values of circAGFG1 in two TNBC cohorts. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circAGFG1 on tumor growth and metastasis in TNBC. Mechanistically, fluorescent in situ hybridization, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between circAGFG1 and miR-195-5p in TNBC.ResultsWe found that circAGFG1 was evidently up-regulated in TNBC, and its level was correlated with clinical stage, pathological grade and poor prognosis of patients with TNBC. The results indicated that circAGFG1 could promote TNBC cell proliferation, mobility and invasion as well as tumorigenesis and metastasis in vivo. Mechanistic analysis showed that circAGFG1 may act as a ceRNA (competing endogenous RNA) of miR-195-5p to relieve the repressive effect of miR-195-5p on its target cyclin E1 (CCNE1).ConclusionsOur findings suggest that circAGFG1 promotes TNBC progression through circAGFG1/miR-195-5p/CCNE1 axis and it may serve as a new diagnostic marker or target for treatment of TNBC patients.
| S-EPMC6325825 | biostudies-literature
Project description:BackgroundTriple-negative breast cancer (TNBC) is one of the most aggressive breast cancer (BC) subtypes. Circular ribonucleic acids (circRNAs) are a class of novel stable and conserved forms of ribonucleic acids (RNAs). circRNAs have been documented to be involved in multiple diseases, especially malignancies, through a competing endogenous RNA (ceRNA) mechanism. However, few studies have been conducted on the function of circRNAs in TNBC. Previously, hsa_circ_0006220 was found to be downregulated in BC tissues. The present study sought to explore the mechanism of hsa_circ_0006220 in TNBC progression.MethodsA real-time polymerase chain reaction (PCR) was used to validate the expression of hsa_circ_0006220 in TNBC tissues and cells. In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), wound-healing and Transwell assays were conducted to measure the inhibition effects of hsa_circ_0006220 on TNBC cells in vitro. Further, a dual-luciferase reporter assay was performed to confirm the interaction between hsa_circ_0006220 and miR-197-5p. A mimic and an inhibitor of miR-197-5p were constructed to confirm the downstream mechanism of hsa_circ_0006220 in TNBC cells.ResultsHsa_circ_0006220 was more downregulated in TNBC than other subtypes of BC tissues and cell lines. In vitro data showed that hsa_circ_0006220 remarkably inhibited the proliferation, migration, and invasion of TNBC cells. Further, hsa_circ_0006220 was confirmed to be a sponge of miR-197-5p, and to indirectly regulate CDH19 expression. A rescue assay indicated the biological function of the hsa_circ_0006220/miR-197-5p/CDH19 pathway in TNBC cells.Conclusionshsa_circ_0006220 plays an inhibitory role in TNBC progression. It might be a potential diagnostic marker and therapeutic target for TNBC patients.
| S-EPMC8421961 | biostudies-literature
Project description:Circular RNAs (circRNAs) are regarded as pivotal regulators in bone metabolism. However, the role of circRNAs in osteoblast mineralization remains largely unknown. Herein, we explored the expression profiles of circRNAs in 4 groups of osteoblasts with varying mineralization processes. Hsa_circ_0008500 (circ8500), which is upregulated in the RNA-seq data, is sifted through 194 candidate circRNAs in osteoblasts during mineralization. We characterize the features of novel circRNAs and find that the elevated expression of circ8500 promotes osteoblast mineralization. Mechanistically, circ8500 contains a critical binding site for miR-1301-3p. We further show that circ8500 competitively binds miR-1301-3p to abolish its suppressive effect on peptidyl arginine deiminase 4 (PADI4). PADI4 works as a binding partner of RUNX2 and stabilizes its protein expression levels by inhibiting the ubiquitin-proteasome pathway. This work provides new insights on the circRNA patterns in osteoblasts and the role of PADI4 in matrix mineralization.
| S-EPMC7759526 | biostudies-literature
Project description:BackgroundAn increasing number of studies have shown that circular RNAs (circRNAs) play important roles in the regulation of tumor progression. Therefore, we explored the expression characteristics, function, and related mechanism of the newly identified circNALCN in glioma.MethodsRNA sequencing was used to analyze the expression profiles of circRNAs in brain tissue from five glioma cases and four normal controls. Quantitative real-time polymerase chain reaction was implemented to examine the levels of circNALCN, miR-493-3p, and phosphatase and tensin homolog (PTEN). Cell counting kit 8 assays were performed to analyze cell proliferation, and cell migration was assessed by the wound healing test and Transwell assay. Dual-luciferase reporter, fluorescence in situ hybridization, and RNA pulldown assays were performed to confirm the role of circNALCN as an miR-493-3p sponge, weakening the inhibitory effect of miR-493-3p on target PTEN expression.ResultsThe downregulated expression of circNALCN was observed in both glioma tissues and cell lines. CircNALCN expression was negatively correlated with World Health Organization grade and overall survival in patients with glioma. Functionally, the overexpression of circNALCN significantly inhibited the proliferation and migration of glioma cells, whereas miR-493-3p mimics counteracted these effects. The mechanistic analysis demonstrated that circNALCN acted as a competing endogenous RNA for miR-493-3p to relieve the repressive effects of miR-493-3p on its target, PTEN, suppressing glioma tumorigenesis.ConclusionsCircNALCN inhibits the progression of glioma through the miR-493-3p/PTEN axis, providing a developable biomarker and therapeutic target for glioma patients.
| S-EPMC8194043 | biostudies-literature
Project description:Circular RNAs (circRNAs), a new category of noncoding RNA, have emerged in recent years as novel biomolecules with important biological functions. Increasing evidence and reports have revealed that circRNAs play an important role in human carcinogenesis and tumor progression. Gastric cancer (GC) is one of the most prevalent life-threatening malignancies worldwide, and in the present study, a novel circRNA molecule (circRIMS) was shown to be associated GC metastasis using next-generation sequencing. CircRIMS remarkably promoted GC cell metastasis in vitro, functioning as a sponge for hsa-miR-148a-5p and hsa-miR-218-5p. In addition, the results of rescue experiments showed that hsa-miR-148a-5p and hsa-miR-218-5p mimics could reverse the tumor-promoting roles of circRIMS in GC. Thus, circRIMS has potential as an early biomarker for use in predicting invasive metastasis in GC and to guide clinical diagnosis and treatment for precision medicine.
| S-EPMC7495717 | biostudies-literature
Project description: Not available
| S-EPMC10752482 | biostudies-literature
Project description:Purpose:Circular RNAs (circRNAs) have been found to regulate several human tumors. The present study was to explore the mechanism of hsa_circ_0087862 in regulating non-small cell lung cancer (NSCLC). Methods:Totally 102 NSCLC cases were enrolled. NCI-H1359 and A549 cells were transfected. Cells viability, apoptosis, migration and invasion were determined by CCK-8 assay, flow cytometry, scratch test and transwell experiment, respectively. Luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were performed. Xenograft tumor experiments were performed using nude mice. hsa_circ_0087862, miR-1253 and RAB3D expression in tissues/cells were detected by qRT-PCR. RAB3D and Ki67 protein expressions in cells/tissues were researched by Western blot and immunohistochemistry. Apoptosis of xenograft tumor tissue cells was detected using Tunel assay. Results:hsa_circ_0087862 was significantly up-regulated in NSCLC patients, which was associated with poor prognosis (P < 0.05). hsa_circ_0087862 down-regulation prominently weakened NSCLC cells viability, migration, invasion and enhanced apoptosis (P < 0.01). hsa_circ_0087862 overexpression exhibited the opposite results in NSCLC cells. miR-1253 was sponged by hsa_circ_0087862. miR-1253 expression in NSCLC tissues was negatively correlated with hsa_circ_0087862 (P < 0.001). RAB3D expression in NSCLC was directly inhibited by miR-1253. miR-1253 down-regulation or RAB3D overexpression dramatically reversed NSCLC cells phenotype induced by hsa_circ_0087862 down-regulation. hsa_circ_0087862 down-regulation markedly inhibited tumor growth in vivo (P < 0.01). In xenograft tumor tissues, hsa_circ_0087862 down-regulation obviously decreased expression of RAB3D, Ki67 and increased apoptosis. Conclusion:hsa_circ_0087862 acted as an oncogene in NSCLC by targeting miR-1253/RAB3D.
| S-EPMC7138622 | biostudies-literature
Project description:Inactivation of p53 contributes significantly to the dismal prognosis of breast tumors, most notably triple-negative breast cancers (TNBCs). How the relief from p53 tumor suppressive functions results in tumor cell aggressive behavior is only partially elucidated. In an attempt to shed light on the implication of microRNAs in this context, we discovered a new signaling axis involving p53, miR-30a and ZEB2. By an in silico approach we identified miR-30a as a putative p53 target and observed that in breast tumors reduced miR-30a expression correlated with p53 inactivation, lymph node positivity and poor prognosis. We demonstrate that p53 binds the MIR30A promoter and induces the transcription of both miRNA strands 5p and 3p. Both miR-30a-5p and -3p showed the capacity of targeting ZEB2, a transcription factor involved in epithelial-mesenchymal transition (EMT), tumor cell migration and drug resistance. Intriguingly, we found that p53 does restrain ZEB2 expression via miR-30a. Finally, we provide evidence that the new p53/miR-30a/ZEB2 axis controls tumor cell invasion and distal spreading and impinges upon miR-200c expression. Overall, this study highlights the existence of a novel axis linking p53 to EMT via miR-30a, and adds support to the notion that miRNAs represent key elements of the complex network whereby p53 inactivation affects TNBC clinical behavior.
| S-EPMC6262018 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) are related to the pathogenesis and progression of triple-negative breast cancer (TNBC). The aim of this study was to investigate the role and mechanism of hsa_circ_0001925 in TNBC progression.MethodsHsa_circ_0001925, microRNA (miR)-1299 and Yin Yang 1 (YY1) levels were examined in TNBC via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, wound healing assay and tube formation assay were conducted to estimate the effects of hsa_circ_0001925 on malignant phenotypes of TNBC tumors. Several protein levels were measured with western blot. The regulatory relationship between miR-1299 and hsa_circ_0001925 or YY1 was validated using a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft assay was used to estimate the effect of hsa_circ_0001925 in TNBC in vivo.ResultsHsa_circ_0001925 and YY1 levels were upregulated, while miR-1299 abundance was downregulated in TNBC tissues and cells. Hsa_circ_0001925 silencing constrained cell proliferation, migration and angiogenesis whereas it promoted apoptosis in vitro, and hsa_circ_0001925 silencing significantly curbed xenograft tumor growth in vivo. Hsa_circ_0001925 acted as a miRNA sponge for miR-1299. Hsa_circ_0001925 decreased YY1 expression by sponging miR-1299. MiR-1299 downregulation alleviated the effects of hsa_circ_0001925 knockdown on BC progression. MiR-1299 interacted with the 3' untranslated region (3' UTR) of YY1, and YY1 overexpression partly reversed the effects of miR-1299 overexpression on BC progression.ConclusionOur findings showed that hsa_circ_0001925 mediated TNBC progression via regulating miR-1299/YY1 axis, providing a potential target for BC treatment.
| S-EPMC10008682 | biostudies-literature
Project description:As an intriguing class of RNA, circular RNAs (circRNAs) are vital mediators of various diseases including cancers. However, the biological role and underlying mechanism of the majority of circRNAs are still ambiguous in the progression of triple-negative breast cancer (TNBC). In this study, we characterized and further investigated hsa_circ_0009362 (circGNB1) by reanalyzing the circRNA microarray profiling in our previous study. Validating by qRT-PCR, circGNB1 was overexpressed in TNBC cell lines and high expression of circGNB1 was associated with worse clinical features and survival outcomes. The expression of circGNB1 was positively correlated with tumor size and clinical stage, and high expression of circGNB1 was an independent risk factor for TNBC patients. Cell proliferation, colony formation, wound-healing and mouse xenograft assays were carried out to investigate the functions of circGNB1. Both in vitro and in vivo assays revealed that knockdown of circGNB1 significantly suppressed cell proliferation, migration and tumor growth. Subsequently, we performed luciferase reporter assays and RNA immunoprecipitation assays to elucidate the underlying molecular mechanism of circGNB1. The results showed that circGNB1 sponges miR-141-5p and facilitates TNBC progression by upregulating IGF1R. Altogether, our study demonstrated the pivotal role of circGNB1-miR-141-5p-IGF1R axis in TNBC growth and metastasis though the mechanism of competing endogenous RNAs. Therefore, circGNB1 may have the potential to be a therapeutic target and novel prognostic biomarker for TNBC.
| S-EPMC7066119 | biostudies-literature