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Osteosarcoma (OS) is a common type of bone tumor, present worldwide, that has distal metastasis ability. Although continuous development in cancer therapy has taken place, there are still no effective metastasis-curbing strategies for OS available. Hence, a better understanding of the biological characteristics and molecular mechanisms of OS carcinogenesis is urgently needed. Long noncoding RNAs (lncRNAs) have captured great interest among cancer scientists with considerable potential implications for cancer treatment. In this study, we found that lncRNA JPX was up-regulated in OS tissues and cells. We subsequently examined the functional role of JPX in OS cells through knocked-down JPX by using siRNA. JPX down-regulation was observed to suppress OS cell proliferation, migration and invasion. Furthermore, it was verified that JPX acts as a sponge for miR-33a-5p, and that JPX regulated OS cell proliferation, migration and invasion through miR-33a-5p. Moreover, down-regulation of miR-33a-5p in OS contributed to PNMA1 upregulation, and PNMA1 depletion inhibited OS cell proliferation, migration and invasion in vitro. Taken together, our data support an important role of JPX in regulating OS cell proliferation, invasion and migration that highlights JPX may be a potential therapeutic target for OS.
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Aim: T-regulatory (Treg)/T-helper (Th) 17 imbalance contributes to the pathogenesis of allergic rhinitis (AR). Long non-coding RNAs (lncRNAs) participate in the progression of AR. Herein, the effect of lncRNA JP X on Treg/Th17 balance in AR was explored.Methods: CD4+ T cells were isolated from patients with AR and healthy control. The percentage of Treg and Th17 cells were examined by flow cytometry. The levels of JP X, miR-378g, CCL5, T GF-ß, and IL-17A were tested using qRT-P CR. The protein expression of Foxp3 and RORγt was measured by western blot.Results: The data showed that an imbalance of Treg/Th17 was associated with AR. Upregulation of JP X was found in AR, and knockdown of which improved the imbalance of Treg/Th17. Furthermore, JP X functioned as a sponge of miR-378g to upregulate CCL5. Inhibition of miR-378g reversed the effects on Treg/Th17 induced by silencing of JP X. Moreover, overexpression of CCL5 reversed miR-378g-induced effects.Conclusion: In conclusion, depletion of JP X promoted Treg/Th17 balance in AR via regulating the miR-378g/CCL5 axis. The findings provided a novel therapeutic insight for AR.
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Quimiocina CCL5 , MicroARNs , ARN Largo no Codificante , Rinitis Alérgica , Linfocitos T Reguladores , Células Th17 , Quimiocina CCL5/genética , Humanos , MicroARNs/genética , ARN Largo no Codificante/genética , Rinitis Alérgica/genética , Linfocitos T Reguladores/inmunología , Células Th17/inmunologíaRESUMEN
With the aggravation of global aging, the rapid rise in the obesity rate, and the increasing number of patients with intervertebral disc degeneration (IDD), the principles and mechanism of this disease remain unclear. This study explored the molecular mechanism of IDD treatment through interactions of the lncRNA-miRNA-mRNA-signaling pathways and the effects on the proliferation and apoptosis of human nucleus pulposus cells (HNPCs) cultured in vitro. Our study revealed that lncRNA JPX is expressed at low levels in HNPCs under normoxic conditions. Luciferase and RNA pull-down assays were used to verify that lncRNA JPX directly bound to miR-18a-5p and influenced HNPC proliferation and apoptosis. Subsequently, a luciferase assay confirmed the direct binding of miR-18a-5p to HIF-1α and demonstrated a negative correlation between miR-18a-5p and HIF-1α. In addition, the HIF-1α antagonist reversed the inhibition of the Hippo-YAP pathway by the miR-18a-5p inhibitor. In conclusion, overexpression of lncRNA JPX upregulated HIF-1α by inhibiting the expression of miR-18a-5p, thereby inhibiting the Hippo-YAP pathway. By inhibiting this pathway, JPX overexpression promoted the proliferation of HNPCs and decreased their apoptosis. Therefore, the lncRNA JPX is a potential new target.
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Apoptosis , Núcleo Pulposo/citología , ARN Largo no Codificante/genética , Transducción de Señal , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Línea Celular , Proliferación Celular , Vía de Señalización Hippo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Núcleo Pulposo/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Largo no Codificante/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Señalizadoras YAPRESUMEN
BACKGROUND: Lung cancer is the most frequently diagnosed cancer. Of all lung cancers, 80-85% are verified as non-small-cell lung cancer (NSCLC). Just proximal to X-inactive specific transcript (JPX), functions as lncRNA, contributed to tumor progression and suggested a poor prognosis in NSCLC. However, the pathogenesis of JPX involved in NSCLC is still unclear. METHODS: The expressions of JPX, miR-5195-3p, and Vascular endothelial growth factor A (VEGFA) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Proliferation, colony number, apoptosis, invasion, and migration were analyzed by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, transwell, and wound healing assays, severally. The protein levels of VEGFA, E-cadherin, N-cadherin, and Vimentin were detected by Western blot assay. The interaction between JPX, miR-5195-3p and VEGFA was predicted by starBase, and then verified by the dual-luciferase reporter, RNA Immunoprecipitation (RIP) and RNA pull-down assay. The biological role of JPX on NSCLC tumor growth was assessed by the xenograft tumor model in vivo. RESULTS: JPX and VEGFA were upregulated, and miR-5195-3p was downregulated in NSCLC. JPX induced proliferation, colony number, invasion, migration, epithelial-mesenchymal transition (EMT), and inhibited apoptosis of NSCLC cells. JPX is directly bound to miR-5195-3p. JPX regulated NSCLC cell proliferation, apoptosis and EMT by modulating miR-5195-3p. miR-5195-3p hindered NSCLC cells proliferation, EMT and accelerated apoptosis by directly targeting VEGFA. JPX silencing hindered the cell growth of NSCLC in vivo. CONCLUSION: JPX facilitated proliferation, colony number, invasion, migration, EMT, and repressed apoptosis by miR-5195-3p/VEGFA axis, offering a possible therapeutic strategy for NSCLC.
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OBJECTIVES: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with high incidence. Numerous reports have elucidated that long non-coding RNAs (lncRNAs) serve as crucial regulatory factors in various diseases including cancer. Nonetheless, the role of lncRNA JPX in OSCC is still not elaborated. SUBJECTS AND METHODS: In our research, we detected the expression of lncRNA JPX through qRT-PCR. Colony formation, EdU staining, Transwell, TUNEL, and caspase-3 activity assays were applied for estimating the function of lncRNA JPX in OSCC. RIP, pull-down, and luciferase reporter experiments were adopted to examine the interrelations between lncRNA JPX, miR-944, and CDH2. RESULTS: LncRNA JPX was discovered as highly expressed in OSCC cells. Silencing lncRNA JPX restrained OSCC cell proliferation, migration, and invasion. Interestingly, lncRNA JPX bound with miR-944 and then augmented CDH2 via a competing endogenous RNA (ceRNA) mechanism. Importantly, overexpressed CDH2 recovered the suppression of silenced lncRNA JPX on the oncogenic behaviors of OSCC cells. CONCLUSIONS: In short, lncRNA JPX contributes to OSCC cell proliferation, migration, and invasion via miR-944/CDH2 axis, which offers a new direction for potential targeted treatment of OSCC.