Knockdown hsa_circ_0063526 inhibits endometriosis progression via regulating the miR-141-5p / EMT axis and downregulating estrogen receptors.
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ABSTRACT:
SUBMITTER: Wei Z
PROVIDER: S-EPMC8751610 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:BackgroundDysregulation of circular RNAs (circRNAs) is associated with bladder cancer progression. Nevertheless, the mechanisms of circRNA centrosomal protein 128 (circCEP128) underlying bladder cancer progression remain poorly understood.MethodsThe levels of circCEP128, microRNA-515-5p (miR-515-5p) and syndecan-1 (SDC1) were determined via reverse transcription-quantitative polymerase chain reaction or Western blot. The effects of circCEP128, miR-515-5p and SDC1 on bladder cancer progression were investigated via MTT and colony formation assays, flow cytometry and transwell analysis and subcutaneous xenograft experiments. The interactions between miR-515-5p and circCEP128 or SDC1 were examined through bioinformatics prediction and luciferase reporter assay.ResultscircCEP128 and SDC1 were highly expressed and miR-515-5p was low expressed in bladder cancer tissues and cells. circCEP128 knockdown hindered cell proliferation, migration and invasion and promoted cell apoptosis in bladder cancer. circCEP128 loss increased miR-515-5p expression through direct interaction in bladder cancer cells. MiR-515-5p depletion mitigated the influences of circCEP128 knockdown on bladder cancer cell phenotypes. SDC1 was a direct target of miR-515-5p. circCEP128 positively regulated SDC1 expression via miR-515-5p. MiR-515-5p restrained the malignant progression of bladder cancer cells by decreasing SDC1 expression. circCEP128 knockdown hindered the growth of bladder cancer xenograft tumors by up-regulating miR-515-5p and down-regulating SDC1.ConclusioncircCEP128 knockdown hampered the tumorigenesis and progression of bladder cancer by regulating miR-515-5p/SDC1 axis in vitro and in vivo, deepening our understanding on the molecular mechanisms of circCEP128 in bladder cancer.
| S-EPMC8020055 | biostudies-literature
Project description:Purpose Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been revealed to involve in the progression of CRC. However, the precise mechanisms of PVT1 in action remain unclear. Methods The expression of PVT1, microRNA-106b-5p (miR-106b-5p) and four jointed box 1 (FJX1) was measured using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot, respectively. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (?z-y1)-3,5-di-phenytetrazoliumromide assay. Transwell assay was used to determine cell migration and invasion. The correlation between miR-106b-5p and PVT1 or FJX1 was confirmed using luciferase reporter assay. The effects of PVT1 in vivo were assessed using mice xenograft model. Results PVT1 was up-regulated in CRC tissues and cell lines, especially in CRC tissues with high-grade, and highly expressed PVT1 predicted worse prognosis. Functional experiments demonstrated that PVT1 deletion inhibited CRC cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. MiR-106b-5p was confirmed to be a target of PVT1, and inhibition of miR-106b-5p reversed the inhibitory effects of PVT1 knockdown on CRC cell malignant phenotypes. In addition, we found miR-106b-5p directly targeted FJX1, and miR-106b-5p-mediated inhibition on CRC cell proliferation, migration and invasion was attenuated by FJX1 up-regulation. Importantly, it was also proved that PVT1 could indirectly regulate FJX1 expression via targeting miR-106b-5p. Conclusion Knockdown of PVT1 impaired cell proliferation, migration and invasion in CRCs via regulating miR-106b-5p/FJX1 axis, which provided a novel insight into the development of therapeutic strategies for CRC patients.
| S-EPMC7520100 | biostudies-literature
Project description:Background:Long noncoding RNAs play essential roles in regulating drug resistance in cancers. However, how and whether lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) could mediate cisplatin resistance in ovarian cancer remain poorly understood. Patients and Methods:Eighteen cisplatin-sensitive and 19 cisplatin-resistant patients with ovarian cancer were recruited. Cisplatin-resistant ovarian cancer cells were used for this study. The expression levels of NEAT1, microRNA (miR)-770-5p and poly adenosine diphosphate-ribose polymerase 1 (PARP1) were detected by quantitative real-time polymerase chain reaction or Western blot. Cisplatin resistance was assessed by the half-maximal inhibitory concentration (IC50) of cisplatin, cell viability and apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, flow cytometry and Western blot, respectively. The target association between miR-770-5p and NEAT1 or PARP1 was investigated by dual-luciferase reporter assay. The xenograft model was used to investigate cisplatin resistance in vivo. Results:NEAT1 expression is elevated in cisplatin-resistant ovarian cancer tissues and cells. Knockdown of NEAT1 repressed cisplatin resistance by decreasing the IC50 of cisplatin, cell viability and increasing apoptosis. MiR-770-5p was bound to NEAT1 and PARP1 was confirmed as a target of miR-770-5p. MiR-770-5p inhibition or PARP1 restoration could abate the effect of NEAT1 silencing on cisplatin resistance in cisplatin-resistant ovarian cancer cells. Moreover, NEAT1 knockdown reduced PARP1 expression by increasing miR-770-5p. Interference of NEAT1 decreased xenograft tumor growth by regulating miR-770-5p and PARP1. Conclusion:Knockdown of NEAT1 inhibited cisplatin resistance in ovarian cancer cells by up-regulating miR-770-5p and down-regulating PARP1, providing a new target for improving the efficacy of cisplatin-based therapy in ovarian cancer.
| S-EPMC7434570 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. Long noncoding RNAs (lncRNAs) have been identified to be associated with many diseases including tumors, and involved in the regulation of a wide array of pathophysiological processes. Small nucleolar RNA host gene 16 (SNHG16), also known as noncoding RNA expressed in aggressive neuroblastoma, was newly identified as a potential oncogene in many cancers. However, its role in ESCC has not been investigated. In the current study, the level of SNHG16 in the ESCC tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR). Then loss-of-function assays were performed to explore the biological effects of SNHG16 in ESCC cell. Based on the online database analysis tools, we uncovered that miR-140-5p could interact with SNHG16 and the level of miR-140-5p was inverse correlated with SNHG16 in ESCC specimens. Moreover, RIP, RNA pulldown system and dual luciferase reporter assay further provided evidence that SNHG16 directly targets miR-140-5p by binding with microRNA binding site harboring in the SNHG16 sequence. Furthermore, bioinformatics analysis revealed that ZEB1 is a target of miR-140-5p in ESCC. Collectively, our findings suggested that SNHG16 could act as an oncogenic lncRNA that promotes tumor progression through acting as an endogenous 'sponge' by competing with miR-140-5p, thereby regulating target ZEB1.
| S-EPMC5787416 | biostudies-literature
Project description:BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of death because of its high incidence and mortality, which is chiefly resulted from cigarette smoke exposure. A large number of studies show that circular RNA (circRNA) participates in regulating COPD process. This study aims to reveal the role of circRNA ankyrin repeat domain 11 (circANKRD11) in cigarette smoke extract (CSE)-induced cell apoptosis, inflammation, and oxidative stress.MethodsThe expression of circANKRD11, microRNA-145-5p (miR-145-5p) and bromodomain-containing 4 (BRD4) mRNA was detected by quantitative real-time polymerase chain reaction. The expression of apoptosis-related proteins and BRD4 protein was determined by Western blot. Cell apoptosis was detected by flow cytometry and Western blot. Cell inflammation was demonstrated by determining the levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) through enzyme-linked immunosorbent assay. Oxidative stress was investigated by the reactive oxygen species (ROS) and malondialdehyde (MDA) determination assays as well as superoxide dismutase (SOD) activity assay. The binding relationship between miR-145-5p and circANKRD11 or BRD4 was predicted by circinteractome or MicroT_CDS online database, and identified by dual-luciferase reporter, RNA immunoprecipitation or RNA pull-down assay.ResultsCircANKRD11 and BRD4 expression were increased, whereas miR-145-5p expression was decreased in the lung tissues of smokers with or without COPD and CSE-induced HPMECs compared with the lung tissues of non-smokers as well as untreated HPMECs, respectively. CircANKRD11 silencing ameliorated CSE-induced cell apoptosis, inflammation, and oxidative stress. CircANKRD11 acted as a sponge of miR-145-5p, and regulated CSE-induced cell injury via sponging miR-145-5p. Additionally, miR-145-5p mimics protected against CSE-induced cell injury through targeting BRD4.ConclusionCircANKRD11 absence protected HPMECs from CSE-induced injury by regulating BRD4 through associating with miR-145-5p, which demonstrated that circANKRD11 had the potential to act as a diagnosis biomarker for smoker-caused COPD.
| S-EPMC8021255 | biostudies-literature
Project description:Circular RNAs (circRNAs) have been reported to be related to the development of human cancers. However, the function of circ-FOXM1 in non-small cell lung cancer (NSCLC) was largely unknown. Here, we revealed the role and functional mechanism of circ-FOXM1 in NSCLC progression. The relative expression of circ-FOXM1, microRNA-149-5p (miR-149-5p), and autophagy-related 5 (ATG5) was determined by quantitative real-time polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assay were employed to assess cell viability, apoptosis, and migration, respectively. The relative protein expression was detected by western blot. Furthermore, mouse xenograft was carried out to analyze the effect of circ-FOXM1 on tumor growth in vivo. In addition, the interaction between miR-149-5p and circ-FOXM1 or ATG5 was predicted by Starbase3.0 and confirmed by the dual-luciferase reporter assay and RNA pull-down assay. Circ-FOXM1 and ATG5 levels were upregulated, while the miR-149-5p level was downregulated in NSCLC tissues and cells. Circ-FOXM1 knockdown suppressed NSCLC cell viability, migration, and autophagy, and induced cell apoptosis. Interestingly, circ-FOXM1 targeted miR-149-5p to upregulate the ATG5 level. Moreover, circ-FOXM1 exerted function through repressing miR-149-5p expression, and miR-149-5p exerted function via inhibiting ATG5 expression. Our results suggested that circ-FOXM1 knockdown attenuated the development of NSCLC through modulating the miR-149-5p/ATG5 axis, providing a theoretical basis for the therapy of NSCLC.
| S-EPMC7889128 | biostudies-literature
Project description:BackgroundColorectal cancer (CRC) poses a heavy threat to human health owing to its high incidence and mortality. Circular RNAs (circRNAs) were investigated to participate in the progression of CRC, whereas there was no revenant data on the CRC process regulated by hsa_circ_0000231. This study aimed to explore the effects of hsa_circ_0000231 on CRC progression and underneath regulatory mechanism.MethodsThe expression levels of hsa_circ_0000231, miR-502-5p, and Myosin VI (MYO6) mRNA were detected by quantitative real time polymerase chain reaction (qRT-PCR). Western blot was employed to determine the protein expression levels of MYO6 and proliferating cell nuclear antigen (PCNA). The effects of hsa_circ_0000231 on cell proliferation, apoptosis, migration, and invasive in CRC were determined by cell counting kit-8 proliferation (CCK-8) and colony formation assays, flow cytometry analysis, wound-healing assay, and transwell invasion assay, respectively. Glucose uptake and lactate production were severally illustrated by glucose assay kit and lactate assay kit. The relationship between miR-502-5p and hsa_circ_0000231 or MYO6 was predicted by circular RNA interactome or targetScan online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo tumor formation assay was carried out to determine the effects of hsa_circ_0000231 knockdown on tumor growth in vivo.ResultsHsa_circ_0000231 expression was dramatically upregulated while miR-502-5p was obviously downregulated in CRC tissues and cells compared with control groups. Hsa_circ_0000231 knockdown repressed the expression levels of MYO6 and PCNA protein. Functionally, hsa_circ_0000231 knockdown repressed cell glycolysis, proliferation, migration and invasion, and induced cell apoptosis, whereas these effects were decreased by miR-502-5p inhibitor. Mechanistically, hsa_circ_0000231 acted as a sponge of miR-502-5p and miR-502-5p bound to MYO6. Furthermore, hsa_circ_0000231 knockdown decreased tumor volume and weight of CRC in vivo.ConclusionHsa_circ_0000231 knockdown inhibited CRC progression and glycolysis by downregulating MYO6 expression through sponging miR-502-5p, which might provide a theoretical basis in further studying circ_0000231-directed therapy in CRC.
| S-EPMC7526375 | biostudies-literature
Project description:Background:Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Increasing evidence showed that circular RNAs (circRNAs) played critical roles in the progression of CRC. However, the effects and underlying mechanisms of circ_0000512 in CRC progression remain unclear. Methods:The expression levels of circ_0000512, microRNA-296-5p (miR-296-5p) and runt-related transcription factor 1 (RUNX1) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, colony formation, cell cycle distribution and cell apoptosis were detected by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and flow cytometry analysis, respectively. Western blot assay was utilized to measure the protein expression of Cyclin D1, Cleaved Caspase-3 and RUNX1. The interaction between miR-296-5p and circ_0000512 or RUNX1 was predicted by starBase and verified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. The mice xenograft model was established to explore the function of circ_0000512 in vivo. Results:The expression of circ_0000512 was increased in CRC tissues and cells. Knockdown of circ_0000512 suppressed cell viability and colony formation and arrested the cells at the G0/G1 phase while it accelerated apoptosis in CRC cells. Mechanistically, circ_0000512 could increase RUNX1 expression by acting as a molecular sponge of miR-296-5p in CRC cells. Furthermore, miR-296-5p downregulation or RUNX1 overexpression reversed the anti-proliferation and pro-apoptosis effects caused by circ_0000512 knockdown in CRC cells. In addition, circ_0000512 interference inhibited tumor growth by upregulating miR-296-5p and downregulating RUNX1 in vivo. Conclusion:Knockdown of circ_0000512 inhibited cell proliferation and induced apoptosis in CRC cell by regulating miR-296-5p/RUNX1 axis, which might provide a potential therapeutic target for CRC treatment.
| S-EPMC7419622 | biostudies-literature
Project description:Retinoblastoma (RB) is the most common primary intraocular cancer type that occurs during retinal development in childhood. Previous studies have reported that long non-coding RNAs (lncRNAs) are involved in the development of RB. Therefore, the aim of the present study was to investigate the effects and underlying regulatory mechanisms of nuclear paraspeckle assembly transcript 1 (NEAT1) in RB. The expression levels of NEAT1, microRNA (miR)-24-3p and leucine-rich-α-2-glycoprotein (LRG1) were detected using reverse transcription-quantitative PCR (RT-qPCR). Moreover, the protein expression levels of LRG1, matrix metalloproteinase 9, N-cadherin and E-cadherin were detected via western blotting. Furthermore, cell migration and invasion abilities were evaluated via Transwell assays. The targeting relationships between miR-24-3p and NEAT1 or LRG1 were predicted using online software and confirmed via dual-luciferase reporter assay. In the present study, NEAT1 and LRG1 were upregulated, and miR-24-3p was downregulated in RB tissues and cells compared with the corresponding healthy tissues and cells. Moreover, miR-24-3p was identified as a target of NEAT and LRG1 was demonstrated to be a direct target gene of miR-24-3p. Knockdown of NEAT1 or LRG1 significantly suppressed RB cell migration and invasion ability, while the effects were reversed by an miR-24-3p inhibitor. In addition, the downregulation of LRG1 caused by miR-24-3p was restored following the overexpression of NEAT1 in RB cells. It was also demonstrated that NEAT1 knockdown inhibited the epithelial-to-mesenchymal transition (EMT) pathway by inhibiting the expression of LRG via targeting miR-24-3p. In conclusion, the present results suggest that silencing of NEAT1 suppresses cell migration, invasion and the EMT process by downregulating LRG1 expression via sponging miR-24-3p in RB, thus indicating that NEAT1 may be a potential candidate for RB treatment.
| S-EPMC7903428 | biostudies-literature