RESUMO
BACKGROUND: An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) serve as key regulators in tumor development and progression. However, only a few lncRNAs have been functionally characterized in gastric cancer (GC). METHODS: Bioinformatics analysis was conducted to find lncRNAs that are associated with GC metastasis. RNA FISH, RIP, and RNA pull down assays were used to study the complementary binding of LINC01564 complementary to the 3'UTR of transcription factor POU2F1. The transcription activation of LINC01564 by POU2F1 as a transcription factor was examined by ChIP assay. In vitro assays such as MTT, cell invasion assay, and clonogenic assay were conducted to examined the impacts of LINC01564 and POU2F1 on GC cell proliferation and invasion. Experiments in vivo were performed to access the impacts of LINC01564 and POU2F1 on GC metastasis. RESULTS: The results showed that LINC01564 complementary bound to the 3'UTR of POU2F1 to form an RNA duplex, whereby stabilizing POU2F1 mRNA and increasing the enrichment in cells. The level of LINC01564 was also increased by POU2F1 through transcription activation. In vitro assays showed that LINC01564 promoted the proliferation, invasion and migration of GC cells through increasing POU2F1. In vivo experiments indicate the promotion of GC proliferation and metastasis by the interaction between LINC01564 and POU2F1. CONCLUSION: Taken together, our results indicate that the interaction between LINC01564 and POU2F1 promotes the proliferation, migration and invasion of GC cells.
Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Fator 1 de Transcrição de Octâmero/genética , Fator 1 de Transcrição de Octâmero/metabolismo , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Fatores de Transcrição/metabolismoRESUMO
Glioma is the most common and malignant brain tumor with poor prognosis. We investigated the effects of LINC01564 on temozolomide (TMZ) resistance of glioma cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the high expression of LINC01564 in human TMZ-resistant glioma cell lines. Functional experiments verified that LINC01564 and SRSF1 promote the proliferation and TMZ resistance and inhibit the apoptosis of TMZ-treated glioma cells. Iron and ROS detection analyses showed that LINC01564 and SRSF1 suppress ferroptosis in glioma cells. Western blot proved that LINC01564 is positively associated with NFE2L2. Mechanism experiments verified the interaction between SRSF1 and MAPK8 3' UTR. In vitro kinase assays showed that MAPK8 can phosphorylate NFE2L2. Rescue experiments showed that MAPK8 reverses the effect of LINC01564 ablation on cell apoptosis and ferroptosis. Meanwhile, NFE2L2 countervails the effect of MAPK8 ablation on the apoptosis and ferroptosis of glioma cells. Animal experiments proved that LINC01564 and MAPK8 facilitate the TMZ resistance of glioma cells in vivo. In conclusion, LINC01564 promotes the TMZ resistance of glioma cells by upregulating NFE2L2 expression to inhibit ferroptosis, which might offer a new perspective into TMZ treatment of glioma. The diagram of the specific mechanism that LINC01564 promotes the TMZ resistance of glioma cells by upregulating NFE2L2 expression to inhibit ferroptosis.
Assuntos
Neoplasias Encefálicas , Ferroptose , Glioma , Animais , Apoptose/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Proteína Quinase 8 Ativada por Mitógeno , Temozolomida/farmacologiaRESUMO
Background: Hepatocellular carcinoma (HCC) is the most common histologic type of primary liver cancers worldwide. Hepatitis C virus (HCV) infection remains a major risk factor for chronic liver disease, cirrhosis, and HCC. To understand the molecular pathogenesis of HCC in chronic HCV infection, many molecular markers are extensively studied, including long noncoding RNAs (lncRNA). Objective: To evaluate the expression levels of lncRNAs (LINC01564, RAMS11), CBX4, and TOP2A in patients with chronic HCV infection and patients with HCC on top of chronic HCV infection and correlate these levels with the clinicopathological features of HCC. Subjects and Methods: One hundred and fifty subjects were enrolled in this study and divided into three groups: group I included 50 patients with HCC on top of chronic hepatitis C (CHC), group II included 50 patients with CHC only, and group III included 50 healthy individuals as a control group. LncRNAs relative expression level was determined by RT-PCR. Results: lncRNA (LINC01564, RAMS11), CBX4, and TOP2A relative expression levels were upregulated in both patient groups compared to controls (p < 0.001*), with the highest levels in the HCC group compared with the CHC group. Additionally, these levels were significantly positively correlated with the clinicopathological features of HCC. Conclusions: The lncRNA (LINC01564, RAMS11), CBX4, and TOP2A relative expression levels were upregulated in CHC patientsin particular, patients with HCC. Thus, these circulatory lncRNAs may be able to serve as promising noninvasive diagnostic markers for HCC associated with viral C hepatitis.