Circ-FOXM1 knockdown suppresses non-small cell lung cancer development by regulating the miR-149-5p/ATG5 axis.
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ABSTRACT:
SUBMITTER: Wei H
PROVIDER: S-EPMC7889128 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:AimPrevious studies have reported that circular RNA (circRNA) is associated with the pathogenesis of CRC. This study was designed to reveal the mechanism of circ-ring finger protein 121 (circ-RNF121) in colorectal cancer (CRC).Materials and methodsThe levels of circ-RNF121, microRNA-1224-5p (miR-1224-5p) and forkhead box M1 (FOXM1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was detected by western blot. Cell proliferation was analyzed by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell colony formation assays. Flow cytometry analysis was performed to investigate cell apoptosis. Cell migration and invasion were investigated by transwell and wound-healing assays. Cell glycolysis was detected using glucose, lactate and ADP/ATP ratio assay kits. The binding relationship between miR-1224-5p and circ-RNF121 or FOXM1 was predicted by starBase online database, and identified by dual-luciferase reporter assay. The impacts of circ-RNF121 silencing on tumor formation in vivo were disclosed by in vivo tumor formation assay.Key findingsCirc-RNF121 and FOXM1 expression were dramatically upregulated, while miR-1224-5p expression was downregulated in CRC tissues or cells compared with control groups. Circ-RNF121 silencing repressed cell proliferation, migration, invasion and glycolysis but induced cell apoptosis in CRC, which were attenuated by miR-1224-5p inhibitor. Additionally, circ-RNF121 acted as a sponge of miR-1224-5p and miR-1224-5p bound to FOXM1. Circ-RNF121 silencing inhibited tumor growth in vivo. Furthermore, circ-RNF121 was secreted through being packaged into exosomes.SignificanceThe finding provided a novel insight into studying circRNA-mediated CRC therapy.
| S-EPMC8572430 | 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:Background:Long noncoding RNA X inactivate-specific transcript (lncRNA XIST) has been identified to contribute to the development and progression of non-small cell lung cancer (NSCLC). Thus, it is important to explore more specific functions and molecular mechanisms of XIST in NSCLC tumorigenesis. Materials and Methods:The expression of XIST, microRNA (miR)-142-5p and paired box 6 (PAX6) was measured using quantitative real-time polymerase chain reaction or Western blot, respectively. Cell proliferation was analyzed using cell counting kit-8 (CCK-8) assay. Flow cytometry was utilized to measure apoptotic cells. Cell migration and invasion were determined by Transwell assay. The interaction between miR-142-5p and XIST or PAX6 was confirmed by the dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo experiments were performed through the murine xenograft model. Results:XIST was elevated in NSCLC, and XIST knockdown suppressed cell proliferation, migration, invasion and induced apoptosis in vitro as well as repressed tumor growth in vivo. MiR-142-5p was a target of XIST, and silencing miR-142-5p reversed the anti-tumor functions mediated by XIST knockdown in NSCLC cells. PAX6 was confirmed to be a target of miR-142-5p, and the inhibitory effects caused by miR-142-5p restoration in NSCLC cell malignant phenotypes were attenuated by PAX6 overexpression. Besides that, XIST could indirectly regulate PAX6 expression by sponging miR-142-5p in vivo and in vitro. Conclusion:XIST suppresses cell tumorigenicity in human NSCLC by regulating miR-142-5p/PAX6 axis, which indicates a novel insight into the pathogenesis of NSCLC and lays a foundation for the molecular therapy of NSCLC.
| S-EPMC7276200 | biostudies-literature
Project description:BackgroundMicroRNAs (miRNAs) are key players in the progression of human cancers. While several miRNAs have been reported to regulate the development of tumors, the molecular mechanisms and roles of miR-149-5p in prostate carcinoma (PCa) remain unclear. Our aim was to investigate the interaction and functions of miR-149-5p and RGS17 in PCa.MethodsMicroarray analysis was performed to identify the key miRNA and gene involved in PCa progression. The expression levels of miRNA and mRNA in PCa tissues and cells were verified by qRT-PCR. MTT assay, BrdU proliferation assay and wound-healing assay were applied to assess the effect of miR-149-5p and RGS17 on PCa cells' viability, proliferation, and migration ability. The association between RGS17 and miR-149-5p was identify using dual-luciferase reporter assay and Western blot assay.ResultsData analysis indicated the reduction of miR-149-5p expression in PCa tissues and cells. Experimental investigations also showed that this miRNA suppressed the viability, proliferation and migration ability of PCa cells. RGS17 was found to be the target of miR-149-5p, and the low expression of miR-149-5p upregulated RGS17 in PCa tissues and cells. The results of the cell-function assays showed that RGS17 acted as an oncogene in PCa even though its promotive effect could be reversed by miR-149-5p.ConclusionThis research confirmed that by targeting and inhibiting RGS17, miR-149-5p could suppress PCa development.
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Project description:Background/Aims:Long noncoding RNAs (lncRNAs) play a critical role in tumorigenesis and progression of ovarian cancer (OC). This study focused on the function and potential mechanism toward LEMD1-AS1 (LEMD1 antisense RNA 1) in the progression of ovarian cancer. Materials and Methods:The expression of LEMD1-AS1 in OC tissues was evaluated in TCGA and Gene Expression Omnibus datasets (GSE119056) and confirmed in OC cell lines via qRT-PCR (quantitative real-time polymerase chain reaction). Then, the location of LEMD1-AS1 in the cytoplasmic and nuclear RNAs extracted from OV cells was detected by qRT-PCR. Cell Counting Kit-8 (CCK-8), colony formation, wound-healing and transwell assays were applied to examine cell viability, proliferation, migration and invasion, respectively. Further, the effect of LEMD1-AS1 on OC tumor growth was determined via subcutaneous xenotransplanted tumor model. The potential target for LEMD1-AS1 was validated via dual-luciferase activity assay, RNA pull-down and RNA immunoprecipitation. Results:The expression of LEMD1-AS1 was decreased in OC tissues and cell lines. Forced overexpression of LEMD1-AS1 inhibited the proliferation, migration and invasion of ovarian cancer cells and transplanted tumor growth in nude mice. We found that LEMD1-AS1 was mainly located in the cytoplasm of OC cells and contained complementary sites of miR-183-5p. Mechanistically, our results showed that LEMD1-AS1 could directly interact with miR-183-5p and tumor protein p53 (TP53). The anti-tumor role of LEMD1-AS1 on OC progression depended on miR-183-5p-mediated TP53 expression. Conclusion:LEMD1-AS1 suppresses OC progression through sponging miR-183-5p and regulation of TP53, suggesting a novel biomarker and target for OC.
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Project description:Serum miR-30c-5p correlates with Parkinson's disease (PD), yet its role has not been illustrated. This research analyzed the function of miR-30c-5p in PD. The behavioral evaluation was performed on MPTP-treated PD mice transfected with miR-30c-5p agomiR, antagomiR, siATG5, or 3-MA (an autophagy inhibitor). Oxidative stress-related factors, miR-30c-5p, and apoptosis- and autophagy-associated proteins in brain tissues or cells were determined by molecular experiments. Tyrosine hydroxylase (TH) and dopamine metabolic markers were detected using immunofluorescence and Diode Array Detector (DAD), respectively. Effects of miR-30c-5p and its target gene Autophagy-related gene (ATG) 5 protein (ATG5) on MPP+-treated SH-SY5Y cells were determined through a series of molecular experiments. MiR-30c-5p was upregulated but ATG5 was downregulated in PD mice. MiR-30c-5p antagomiR attenuated the decrease of ATG5 in PD mice. MiR-30c-5p antagomiR partly alleviated the behavioral symptoms and inhibited the increases of malondialdehyde (MDA), catalase (CAT), and SOD in PD mice. The levels of Bcl-2, dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), TH, and LC3 II were downregulated in PD mice, while Bax, cleaved caspase-3, P62, and LC3 I were upregulated. However, miR-30c-5p antagomiR partly reversed the levels of these factors in PD mice. 3-MA could block the effects of miR-30c-5p antagomiR on PD mice. MiR-30c-5p antagomiR attenuated apoptosis and induced autophagy in brain tissues of MPTP-treated mice by targeting ATG5. In vitro assay results also showed that silence of ATG5 reduced the protective effect of miR-30c-5p downregulation on the cells. MiR-30c-5p regulates the progression of Parkinson's disease through attenuating ATG5-inhibited apoptosis and -induced autophagy.
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Project description:Circ-BPTF (hsa_circ_0000799) is a novel circular RNA derived from BPTF exons. Although BPTF is a well-studied predecessor gene, the characteristics and functions of circ-BPTF have not yet been reported. Here, we show that expression of circ-BPTF is increased in bladder cancer (BCa) tissues and cell lines compared with noncancerous tissues and cell lines. Consistently, BCa patients with higher expression levels of circ-BPTF were found to have higher tumor grades and poorer prognosis. Functionally, knockdown of circ-BPTF inhibited tumor progression in vitro and in vivo. Mechanistically, a target microRNA of circ-BPTF was confirmed to be miR-31-5p, and miR-31-5p mimics partially reversed the effect of circ-BPTF. Furthermore, RAB27A was predicted and shown to be a target of miR-31-5p, and circ-BPTF attenuated the anti-oncogenic effect of miR-31-5p and consequently enhanced RAB27A expression. In summary, our findings reveal that circ-BPTF promotes BCa progression through the miR-31-5p/RAB27A axis, suggesting that circ-BPTF may be a potential target for BCa treatment.
| S-EPMC6128440 | biostudies-other
Project description:Non-small-cell lung cancer (NSCLC) remains a huge obstacle to human health. Certain circular RNAs endow with crucial regulatory roles in NSCLC progression. Here, we investigated the functional effects of circ_0001821 on cellular behaviors of NSCLC cells and explored the possible mechanism. The expression of circ_0001821, microRNA (miR)-526b-5p, and G protein-coupled receptor kinase 5 (GRK5) was determined by quantitative real-time polymerase chain reaction or Western blot assay. Clonogenicity in NSCLC cells was detected via colony formation assay. Cell migration and invasion were monitored by Transwell assay. Cell sensitivity to paclitaxel (TAX) evaluated by Cell Counting Kit-8 assay. Cell apoptosis was assessed by flow cytometry, caspase-3 activity, and caspase-9 activity. The targeted relationship between miR-526b-5p and circ_0001821 or GRK5 was confirmed by dual-luciferase reporter or RNA pull-down assay. Moreover, the role of circ_0001821 in vivo was examined by xenograft model assay. The results presented that the expression of circ_0001821 and GRK5 was increased, while miR-526b-5p expression was decreased in NSCLC tissues and cells. Circ_0001821 knockdown reduced colony formation ability and metastasis ability but enhanced TAX sensibility and apoptosis of NSCLC cells, which was attenuated by miR-526b-5p inhibition or GRK5 overexpression. Circ_0001821 targeted miR-526b-5p, and miR-526b-5p targeted GRK5. Circ_0001821 could upregulate GRK5 expression by sponging miR-526b-5p. Depletion of circ_0001821 also blocked tumor growth in vivo. In conclusion, the depletion of circ_0001821 inhibited NSCLC progression, at least in part, by modulating the miR-526b-5p/GRK5 axis.
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