CircRPPH1 serves as a sponge for miR-296-5p to enhance progression of breast cancer by regulating FOXP4 expression.
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ABSTRACT:
SUBMITTER: Yang L
PROVIDER: S-EPMC8340247 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA growing body of evidence indicates that abnormal expression of circular RNAs (circRNAs) plays a crucial role by acting as molecular sponges of microRNAs (miRNAs) in various diseases, including cancer. In this study, we explored whether circCCDC85A could function as a miR-550a-5p sponge and influence breast cancer progression.MethodsWe detected the expression of circCCDC85A in breast cancer tissues and cells using fluorescence in situ hybridization (FISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). CCK-8 and colony formation assay were used to detect the proliferative ability of breast cancer cells. Wound healing assay and transwell migration and invasion assays were used to detect the migrative and invasive abilities of breast cancer cells. We also examined the interactions between circCCDC85A and miR-550a-5p using FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Moreover, we performed luciferase reporter assay, qRT-PCR, and Western blot to confirm the direct targeting of miR-550a-5p to MOB1A.ResultsThe expression of circCCDC85A in breast cancer tissues was obviously lower than that in normal breast tissues. Over-expression of circCCDC85A substantially inhibited the proliferative, migrative, and invasive ability of breast cancer cells, while knocking down of circCCDC85A enhanced the aforementioned properties of breast cancer cells. Moreover, enforced expression of circCCDC85A inhibits the oncogenic activity of miR-550a-5p and increases the expression of MOB1A targeted by miR-550a-5p. Further molecular mechanism research showed that circCCDC85A may act as a molecular sponge for miR-550a-5p, thus restoring miR-550a-5p-mediated targeting repression of tumor suppressor MOB1A in breast cancer cells.ConclusionOur findings provide novel evidence that circCCDC85A inhibits the progression of breast cancer by functioning as a molecular sponge of miR-550a-5p to enhance MOB1A expression.
| S-EPMC8725284 | biostudies-literature
Project description:Increasing lines of evidence indicate the role of long non-coding RNAs (LncRNAs) in gene regulation and tumor development. Hence, it is important to elucidate the mechanisms of LncRNAs underlying the proliferation, metastasis, and invasion of lung adenocarcinoma (LUAD). We employed microarrays to screen LncRNAs in LUAD tissues with and without lymph node metastasis and revealed their effects on LUAD. Among them, Linc00426 was selected for further exploration in its expression, the biological significance, and the underlying molecular mechanisms. Linc00426 exhibits ectopic expression in LUAD tissues and cells. The ectopic expression has been clinically linked to tumor size, lymphatic metastasis, and tumor differentiation of patients with LUAD. The deregulation of Linc00426 contributes to a notable impairment in proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the deregulation of Linc00426 could reduce cytoskeleton rearrangement and matrix metalloproteinase expression. Meanwhile, decreasing the level of Linc00426 or increasing miR-455-5p could down-regulate the level of UBE2V1. Thus, Linc00426 may act as a competing endogenous RNA (ceRNA) to abate miR-455-5p-dependent UBE2V1 reduction. We conclude that Linc00426 accelerates LUAD progression by acting as a molecular sponge to regulate miR-455-5p, and may be a potential novel tumor marker for LUAD.
| S-EPMC7732829 | biostudies-literature
Project description:Circular RNAs (circRNAs) play a vital role in the occurrence and development of tumors, including gastric cancer (GC). However, there are still many circRNAs related to GC whose functions and molecular mechanisms remain undetermined. Herein, we discover circRNA RELL1, which has not been investigated in GC, and it is markedly downregulated in GC tissues, which is related with poor prognosis, more pronounced lymph node metastasis and poor TNM stage. After confirming the circular structure of circRELL1, we found that circRELL1 could block cell proliferation, invasion, migration, and anti-apoptosis in patients with GC by a series of in vivo and in vitro function-related studies. Further mechanism investigation demonstrated that circRELL1 could sponge miR-637 and indirectly unregulated the expression of EPHB3 via modulating autophagy activation in GC. Additionally, circRELL1 can be transmitted by exosomal communication, and exosomal circRELL1 suppressed the malignant behavior of GC in vivo and in vitro. Taken together, this study elucidates the suppressive roles of circRELL1/miR-637/EPHB3 axis through autophagy activation in GC progression, inspiring for further understanding of the underlying molecular mechanisms of GC and providing a promising novel diagnostic circulating biomarker and therapeutic target in GC.
| S-EPMC8758736 | biostudies-literature
Project description:Long non coding RNA FOXP4-AS1 exerted crucial functions in various human cancers, while its role in non-small cell lung cancer (NSCLC) remains unclear. A total of 30 pairs of NSCLC tissues and matched adjacent normal tissues were used to evaluate the expression of FOXP4-AS1 and miR-3184-5p. Cell proliferation was assessed by CCK-8 assay and colony formation assay. Cell apoptosis was measured by flow cytometry. Bioinformatic analysis and luciferase reporter assay were performed to determine the regulatory relationship among FOXP4-AS1, miR-3184-5p and EIF5A. The xenograft tumor model was constructed to confirm the function of FOXP4-AS1 in NSCLC progression. The results showed that FOXP4-AS1 was upregulated and miR-3184-5p was downregulated in NSCLC tissues and cell lines. Downregulation of FOXP4-AS1 significantly reduced cell proliferation and induced apoptosis of NSCLC cells in vitro. FOXP4-AS1 could regulated the expression of EIF5A by binding to miR-3184-5p. Rescue experiments showed that downregulation of miR-3184-5p or overexpression of EIF5A obviously attenuated the inhibitory effects of si-FOXP4-AS1 on cell proliferation, as well as the stimulating effects on cell apoptosis. Moreover, knockdown of FOXP4-AS1 could efficiently inhibited tumor development of NSCLC in vivo. Downregulation of FOXP4-AS1 attenuated the progression of NSCLC by regulating miR-3184-5p and EIF5A.
| S-EPMC9306595 | biostudies-literature
Project description:Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. The levels of circ_0000144, miR-623 and G-protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using Western blot. In vivo assays were used to explore the impact of circ_0000144 on tumor growth. Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment.
| S-EPMC7426631 | biostudies-literature
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:BackgroundCircular RNAs (circRNAs) have been documented as key regulators during progression of malignant human cancer, including colorectal cancer (CRC). However, the underlying molecular mechanisms of circNOL10 in CRC remain unclear.MethodsThe real-time quantitative polymerase chain reaction was used to quantify the expression of circNOL10, miR-135a-5p, miR-135b-5p, and Krüppel-like factor 9 (KLF9). Kaplan-Meier curve was employed to assess the relationship between survival time of CRC patients and expression level of circNOL10. Cell ability of proliferation was measured by Cell Counting Kit8 and colony formation assays. Cell-cycle analysis was performed using flow cytometry assay. In addition, migration and invasion of CRC cell were examined with transwell analysis. The protein expression level was measured with Western blot assay. The interaction relationship of different molecules was analyzed by bioinformatics database and confirmed by dual-luciferase reporter, RNA immunoprecipitation, and RNA pulldown assay. The functional role of circNOL10 in vivo was determined by xenograft experiment.ResultsCircNOL10 was decreased in CRC tissues and cells and was associated with poor outcomes. Gain-of-functional experiment revealed that overexpression of circNOL10 constrained proliferation, cell-cycle progression, migration, and invasion of CRC cells, which was abolished by overexpression of miR-135a-5p or miR-135b-5p. Additionally, miR-135a-5p and miR-135b-5p, targets of circNOL10, regulated KLF9 expression in a negative feedback. Consistently, the results of xenograft experiment suggested that overexpression of circNOL10 inhibited tumor growth in vivo.ConclusionIn summary, our results showed that circNOL10 impeded CRC development by mediating proliferation, cell cycle, migration, and invasion by sponging miR-135a-5p and miR-135b-5p, which provided new understanding for CRC treatment.
| S-EPMC7292486 | 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
Project description:As the second largest gynecological cancer, cervical cancer has been widely reported in recent years in which circular RNA is involved in the disease process. We earlier found that the expression of hsa_circ_0000511 in cervical cancer cells increased significantly, but its role in the process of cervical cancer is not clear. The purpose of this study is to explore its possible mechanisms in cervical cancer. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), cell counting kit-8 assay, Transwell test, cell transfection, RNA pull-down assay and dual-luciferase reporter assay, and Western blot analysis were used to detect the expression and distribution of hsa_circ_0000511 in SiHa and HeLa cells, the ability of invasion and proliferation, and the modulated relationships between hsa_circ_0000511 and hsa-mir-296-5p, hsa-mir-296-5p, and HMGA1. hsa_circ_0000511 had the highest expression in SiHa and HeLa cells, and the expression in the cytoplasm was significantly higher than that in the nucleus, and its expression was not affected by RNase R. When hsa_circ_0000511 was silenced, its expression in SiHa and HeLa cells was significantly decreased; the proliferation, invasion, and migration abilities of the two kinds of cells were significantly enhanced; and the protein expression of E-cadherin was significantly upregulated, while the protein expression of N-cadherin was significantly downregulated. The expression of hsa-mir-296-5p was lower in SiHa and HeLa cells; however, its expression was increased when hsa_circ_0000511 was inhibited and decreased when hsa_circ_0000511 was overexpressed, so did the ability of proliferation, invasion, and migration and the protein expression of E-cadherin. Interestingly, the protein expression of HMGA1 also changed in these two cells when hsa-mir-296-5p was inhibited or overexpressed. Our results indicate that the upregulated hsa_circ_0000511 can inhibit the proliferation, invasion, and migration of SiHa and HeLa cells by regulating hsa-mir-296-5p/HMGA1, suggesting that the hsa_circ_0000511/hsa-mir-296-5p/HMGA1 pathway may be a potential target for the treatment of cervical cancer.
| S-EPMC8175136 | biostudies-literature
Project description:Background:Breast cancer (BC) is the most common malignancy among women. Emerging studies have demonstrated that circular RNA (circRNA) zinc finger RNA binding protein (circZFR) serves as a crucial regulator in many human cancers. However, the role and mechanism of circZFR in BC tumorigenesis remain unclear. Methods:The levels of circZFR, miR-578 and hypoxia-inducible factor 1? (HIF1A) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability, colony formation, apoptosis, migration and invasion capacities in vitro were determined by using the Cell Counting Kit-8 (CCK-8), standard colony formation, flow cytometry and transwell assays, respectively. Glucose uptake, lactate product and adenosine triphosphate (ATP) levels of cells in vitro were measured using the commercial human assay kits. Targeted relationships among circZFR, miR-578 and HIF1A in BC cell lines were verified by dual-luciferase reporter and RNA pulldown assays. Animal studies were performed to assess the effect of circZFR on tumor growth in vivo. Results:Our data indicated that circZFR was overexpressed in BC tissues and cells, and the increased circZFR level predicted poor prognosis of BC patients. CircZFR silencing or miR-578 overexpression repressed BC cell viability, colony formation, migration, invasion, and glycolysis and enhanced cell apoptosis in vitro. CircZFR silencing also hampered tumor growth in vivo. Mechanistically, circZFR acted as a sponge of miR-578, and circZFR silencing hindered BC cell malignant behaviors by miR-578. HIF1A was a functional target of miR-578 in regulating BC cell viability, colony formation, migration, invasion, glycolysis and apoptosis in vitro. Furthermore, circZFR modulated HIF1A expression through sponging miR-578. Conclusion:Our findings first identified that the silencing of circZFR suppressed BC malignant progression in vitro via the regulation of the miR-578/HIF1A axis, providing evidence for the crucial involvement of circZFR in BC pathogenesis.
| S-EPMC7437024 | biostudies-literature