RESUMEN
PURPOSE: Ischemic brain injury results in high mortality and serious neurologic morbidity. Here, we explored the role of SNHG15 in modulating neuronal damage and microglial inflammation after ischemia stroke. MATERIALS AND METHODS: The hypoxia/ischemia models were induced by middle cerebral artery occlusion in mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Quantitative real-time PCR (qRT-PCR) and Western blot were conducted to determine the levels of SNHG15, miR-302a-3p, and STAT1/NF-κB. Moreover, gain- or loss-of functional assays of SNHG15 and miR-302a-3p were conducted. MTT assay was used to evaluate the viability of HT22 cells, and the apoptotic level was determined by flow cytometry. Furthermore, enzyme-linked immunosorbent assay was performed to detect oxidative stress and inflammatory mediators in the ischemia cortex and OGD/R-treated BV2 microglia. RESULTS: The SNHG15 and STAT1/NF-κB pathways were both distinctly up-regulated, while miR-302a-3p was notably down-regulated in the ischemia cortex. Additionally, overexpressing SNHG15 dramatically enhanced OGD/R-mediated neuronal apoptosis as well as the expression of oxidative stress and inflammation factors from microglia. In contrast, knocking down SNHG15 or overexpressing miR-302a-3p relieved OGD/R-mediated neuronal apoptosis and microglial activation. Moreover, the rescue experiment testified that overexpressing miR-302a-3p also attenuated SNHG15 up-regulation-induced effects. In terms of the mechanisms, SNHG15 sponged miR-302a-3p and activated STAT1/NF-κB as a competitive endogenous RNA, while miR-302a-3p targeted STAT1 and negatively regulated the STAT1/NF-κB pathway. CONCLUSION: SNHG15 was up-regulated in the hypoxia/ischemia mouse or cell model. The inhibition of SNHG15 ameliorates ischemia/hypoxia-induced neuronal damage and microglial inflammation by regulating the miR-302a-3p/STAT1/NF-κB pathway.
Asunto(s)
MicroARNs , ARN Largo no Codificante , Animales , Apoptosis/genética , Hipoxia , Ratones , MicroARNs/genética , FN-kappa B/genética , FN-kappa B/metabolismo , Neuronas/metabolismo , ARN Largo no Codificante/genética , Factor de Transcripción STAT1/genéticaRESUMEN
Extensive studies have explored the involvements of long noncoding RNAs (lncRNAs) in liver cancer. Limitedly, the concrete function of lncRNA small nucleolar RNA host gene 15 (SNHG15) is still elusive. Therefore, the work was initiated to unearth SNHG15-oriented mechanism in liver cancer. Liver cancer tissues were resected. The connection between SNHG15 expression with prognosis and clinicopathological traits of liver cancer patients was evaluated. Liver cancer cells SMMC-7721 were transfected with restored microRNA (miR)-18b-5p or depleted SNHG15 to discover their effects on the proliferation, migration, invasion, cycle arrest, and apoptosis of SMMC-7721 cells. The transfected SMMC-7721 cells were injected into nude mice for further investigation. SNHG15, miR-18b-5p, and LIM-only 4 (LMO4) expressions in tissues and cells were tested. The regulatory connections among SNHG15, miR-18b-5p, and LMO4 were detected. SNHG15 and LMO4 were overexpressed while miR-18b-5p was downregulated in liver cancer tissues and cells. Up-regulated SNHG15 was connected with inferior prognosis and aggressive behaviors of liver cancer patients. SNHG15 knockdown or miR-18b-5p restoration depressed SMMC-7721 cell growth in vivo and in vitro. SNHG15 bound to miR-18b-5p and miR-18b-5p targeted LMO4. The work has illuminated that silencing SNHG15 represses liver cancer progression by modulating miR-18b-5p and LMO4, indicating the therapeutic potency of SNHG15/miR-18b-5p/LMO4 axis in liver cancer.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas con Dominio LIM/metabolismo , Neoplasias Hepáticas/patología , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Nucleolar Pequeño/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Femenino , Humanos , Proteínas con Dominio LIM/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Increasing evidence implies the participation of long non-coding RNAs (lncRNAs) in chemoresistance to cancer treatment. Their role and molecular mechanisms in breast cancer chemoresistance, nevertheless, are yet not considerably elucidated. In this work, we research the function of small nucleolar RNA host gene 15 (SNHG15) in cisplatin (DDP) resistance of breast cancer and uncover the underlying molecular mechanism. METHODS: SNHG15 and miR-381 expression levels were detected using Quantitative real-time PCR (qRT-PCR) analysis. The functional roles of SNHG15 and miR-381 in breast cancer were determined using MTT assay and flow cytometry analysis. The effect of SNHG15 on miR-381 expression was determined using Luciferase reporter assay, RNA immunoprecipitation (RIP) assay and qRT-PCR analysis. RESULTS: SNHG15 was found to be up-regulated in cisplatin resistant breast cancer tissues and cell lines. Breast cancer patients with high SNHG15 expression had a poor prognosis. SNHG15 silencing enhanced cisplatin sensitivity of MCF-7/DDP and MDA-MB-231/DDP cells. Additionally, SNHG15 could function as a miR-381 sponge. miR-381 overexpression could overcome cisplatin resistance. miR-381 knockdown countered SNHG15 knockdown-mediated enhancement of cisplatin sensitivity in MCF-7/DDP and MDA-MB-231/DDP cells. Besides, SNHG15 knockdown facilitated cisplatin sensitivity of cisplatin resistant breast cancer cells in vivo. CONCLUSION: In summary, SNHG15 knockdown overcame cisplatin resistance of breast cancer by sponging miR-381, providing a novel therapeutic target for breast cancer.
RESUMEN
The incidence and death rate of colorectal cancer (CRC) is very high, which brings great need to understand the early molecular events of CRC. These studies demonstrate that long noncoding RNA (lncRNA) plays an important role in the occurrence and development of human cancer. Small nucleolar RNA host gene 15 (SNHG15) was recently identified as a cancer-related lncRNA. In this study, we aimed to evaluate the function and mechanism of SNHG15 in CRC. The expression of SNHG15 was detected by quantitative RT-PCR (qRT-PCR) in CRC tissues and matched noncancerous tissues (NCTs). CCK-8 assay, colony formation assay, flow cytometric analysis, and nude mouse xenograft mode were used to examine the tumor-promoting function of SNHG15 in vitro and in vivo. The binding relationship between SNHG15, miR-338-3p and the target genes of miR-338-3p were screened and identified by databases, qRT-PCR, dual luciferase reporter assay and western blot. Our results showed that SNHG15 was up-regulated in CRC tissues compared with paired NCTs (P < 0.0001). High level of SNHG15 expression predicted poor prognosis of CRC (P = 0.0051). SNHG15 overexpression could promote cell proliferation and inhibit cell apoptosis. Animal experiments showed that up-regulation of SNHG15 promoted tumor growth in vivo. The results of mechanism experiments showed that SNHG15 could bind to miR-338-3p and block its inhibition on the expression and activity of FOS or RAB14. In conclusion SNHG15 promotes cell proliferation through SNHG15/miR-338-3p/FOS-RAB14 axis in CRC.
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Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Interferencia de ARN , ARN Largo no Codificante/genética , Animales , Apoptosis , Biomarcadores de Tumor , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Humanos , Ratones , Modelos Biológicos , Pronóstico , Proteínas Proto-Oncogénicas c-fos/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas de Unión al GTP rab/genéticaRESUMEN
As a kind of long non-coding RNAs (lncRNAs),small nucleolar RNA host gene 15 (SNHG15) is located on chromosome 7.In recent years,studies have shown that lncRNA SNHG15 is over expressed in various types of cancers such as glioma,thyroid cancer,breast cancer,lung cancer,gastric cancer,colorectal cancer,liver cancer,renal carcinoma,pancreatic cancer,osteosarcoma,and it can promote the proliferation,invasion,metastasis of malignant tumors and lead to poor prognosis of tumor patients through different signal pathways.
