Dataset Information

Long Non-Coding RNA SLC25A21-AS1 Promotes Multidrug Resistance in Nasopharyngeal Carcinoma by Regulating miR-324-3p/IL-6 Axis.

ABSTRACT: Background:Nasopharyngeal carcinoma (NPC), one of the most common types of head and neck tumor, occurred in the epithelial lining of the nasopharynx and is mainly prevalent in Southeast Asia and Southern China. However, the molecular mechanisms of NPC multidrug resistance still remained largely unclear. Methods:The qRT-PCR assay was performed to examine SLC25A21-AS1, miR-324-3p and IL-6 expression in NPC tissues and cell. The CCK8 assay and colony formation assay were used to detect cell growth. In addition, CCK8 assay was performed to detect IC50 values of different drugs in NPC cell. Results:In this study, we found that SLC25A21-AS1 expression was increased in NPC tissues and cell line, and knockdown of SLC25A21-AS1 inhibited cell growth and MDR in NPC cell. Moreover, SLC25A21-AS1 acted as a ceRNA for miR-324-3p and facilitates NPC cell growth and MDR by regulating the miR-324-3p/IL-6 axis. Conclusion:Our findings demonstrated the role of SLC25A21-AS1/miR-324-3p/IL-6 axis in cell growth and MDR in NPC, which might be a potential prognostic and diagnostic marker in NPC patients and provide new insight into the molecular mechanism of MDR in NPC chemotherapy.

SUBMITTER: Wang X

PROVIDER: S-EPMC7264158 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long Non-Coding RNA SLC25A21-AS1 Promotes Multidrug Resistance in Nasopharyngeal Carcinoma by Regulating miR-324-3p/IL-6 Axis.

Wang Xiaoqin X Wang Chunhui C Xu Hong H Xie Hong H

Cancer management and research 20200526

<h4>Background</h4>Nasopharyngeal carcinoma (NPC), one of the most common types of head and neck tumor, occurred in the epithelial lining of the nasopharynx and is mainly prevalent in Southeast Asia and Southern China. However, the molecular mechanisms of NPC multidrug resistance still remained largely unclear.<h4>Methods</h4>The qRT-PCR assay was performed to examine SLC25A21-AS1, miR-324-3p and IL-6 expression in NPC tissues and cell. The CCK8 assay and colony formation assay were used to dete ...[more]

PMID: 32547230

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Project description:BackgroundObesity alters metabolic microenvironment and is thus associated with several tumours. The aim of the present study was to investigate the role, molecular mechanism of action, and potential clinical value of lipid metabolism-related long non-coding RNA (lncRNA) SLC25A21-AS1 in oesophageal squamous cell carcinoma (ESCC).MethodsA high-fat diets (HFDs)-induced obesity nude mouse model was established, and targeted metabolomics analysis was used to identify critical medium-long chain fatty acids influencing the growth of ESCC cells. Transcriptomic analysis of public dataset GSE53625 confirmed that lncRNA SLC25A21-AS1 was a lipid metabolism-related lncRNA. The biological function of lncRNA SLC25A21-AS1 in ESCC was investigated both in vivo and in vitro. Chromatin immunoprecipitation(ChIP)assay, RNA-pull down, mass spectrometry, co-IP, and RNA IP(RIP) were performed to explore the molecular mechanism. Finally, an ESCC cDNA microarray was used to determine the clinical prognostic value of SLC25A21-AS1 by RT-qPCR.ResultsPalmitic acid (PA) is an important fatty acid component of HFD and had an inhibitory effect on ESCC cell lines. LncRNA SLC25A21-AS1 expression was downregulated by PA and associated with the proliferation and migration of ESCC cells in vitro and in vivo. Mechanistically, SLC25A21-AS1 interacted with nucleophosmin-1 (NPM1) protein to promote the downstream gene transcription of the c-Myc in the nucleus. In the cytoplasm, SLC25A21-AS1 maintained the stability of SLC25A21 mRNA and reduced the intracellular NAD+ /NADH ratio by influencing tryptophan catabolism. Finally, we demonstrated that high expression of SLC25A21-AS1 promoted resistance to cisplatin-induced apoptosis and was correlated with poor tumour grade and overall survival.ConclusionsHFD/PA has an inhibitory effect on ESCC cells and SLC25A21-AS1 expression. SLC25A21-AS1 promotes the proliferation and migration of ESCC cells by regulating the NPM1/c-Myc axis and SLC25A21 expression. In addition, lncRNA SLC25A21-AS1 may serve as a favourable prognostic biomarker and a potential therapeutic target for ESCC.

Project description:Rationale: Glioma is the most common primary malignant tumor of human central nervous system, and its rich vascular characteristics make anti-angiogenic therapy become a therapeutic hotspot. However, the existence of glioma VM makes the anti-angiogenic therapy ineffective. SUMOylation is a post-translational modification that affects cell tumorigenicity by regulating the expression and activity of substrate proteins. Methods: The binding and modification of IGF2BP2 and SUMO1 were identified using Ni2+-NTA agarose bead pull-down assays, CO-IP and western blot; and in vitro SUMOylation assays combined with immunoprecipitation and immunofluorescence staining were performed to explore the detail affects and regulations of the SUMOylation on IGF2BP2. RT-PCR and western blot were used to detect the expression levels of IGF2BP2, OIP5-AS1, and miR-495-3p in glioma tissues and cell lines. CCK-8 assays, cell transwell assays, and three-dimensional cell culture methods were used for evaluating the function of IGF2BP2, OIP5-AS1, miR-495-3p, HIF1A and MMP14 in biological behaviors of glioma cells. Meantime, RIP and luciferase reporter assays were used for inquiring into the interactions among IGF2BP2, OIP5-AS1, miR-495-3p, HIF1A and MMP14. Eventually, the tumor xenografts in nude mice further as certained the effects of IGF2BP2 SUMOylation on glioma cells. Results: This study proved that IGF2BP2 mainly binds to SUMO1 and was SUMOylated at the lysine residues K497, K505 and K509 sites, which can be reduced by SENP1. SUMOylation increased IGF2BP2 protein expression and blocked its degradation through ubiquitin-proteasome pathway, thereby increasing its stability. The expressions of IGF2BP2 and OIP5-AS1 were up-regulated and the expression of miR-495-3p was down-regulated in both glioma tissues and cells. IGF2BP2 enhances the stability of OIP5-AS1, thereby increasing the binding of OIP5-AS1 to miR-495-3p, weakening the binding of miR-495-3p to the 3'UTR of HIF1A and MMP14 mRNA, and ultimately promoting the formation of VM in glioma. Conclusions: This study first revealed that SUMOylation of IGF2BP2 regulated OIP5-AS1/miR-495-3p axis to promote VM formation in glioma cells and xenografts growth in nude mice, providing a new idea for molecular targeted therapy of glioma.

Project description:BackgroundEpithelial ovarian cancer (EOC) is a highly prevalent disease that rapidly metastasizes and has poor prognosis. Most women are in the middle or late stages when diagnosed and have low survival rates. Recently, long non-coding RNAs (lncRNAs) were recognized to play pivotal roles in the development of EOC.MethodsThe expression of SLC25A21 antisense RNA 1 (SLC25A21-AS1) and Polypyrimidine Tract Binding Protein 3 (PTBP3) in EOC cells was assessed via qPCR. The proliferation activity of these cells was detected by EdU and Cell counting kit-8 (CCK8) assays, while the death rate of apoptotic cells and the cell cycle were detected by flow cytometry. Detection of cell transfer rate by transwell assay. Protein expression was measured through western blotting. Interactions between SLC25A21-AS1 and PTBP3 were detected through RNA immunoprecipitation (RIP), IF-FISH co-localization experiments and electrophoretic mobility shift assay (EMSA). The in vivo importance of SLC25A21-AS1 as a tumor suppressor modulator was assessed using murine xenograft models.ResultsThe lncRNA SLC25A21-AS1 has negligible expression in ovarian cancer tissues compared with that in normal ovarian tissues. A series of functional experiments revealed that the upregulation of SLC25A21-AS1 markedly blocked the proliferation and metastasis of EOC cells in vitro, while its downregulation had the opposite effect. Overexpression of SLC25A21-AS1 in a nude mouse model of EOC in vivo resulted in slower tumor growth and weakened metastatic potential. Moreover, SLC25A21-AS1 reduced the protein stability of PTBP3 and promoted its degradation. A series of subsequent experiments found that SLC25A21-AS1 inhibits EOC cell proliferation and metastasis by modulating PTBP3 through the ubiquitin-proteasome pathway and that the combination of SLC25A21-AS1 and PTBP3 provides the necessary conditions for the for the function to be realized.ConclusionsOur research reveals the effect of SLC25A21-AS1 in EOC development and suggests SLC25A21-AS1 can serve as a prognostic target by promoting the degradation of PTBP3 to improve patient survival.

Dataset Information

Long Non-Coding RNA SLC25A21-AS1 Promotes Multidrug Resistance in Nasopharyngeal Carcinoma by Regulating miR-324-3p/IL-6 Axis.

Publications

Long Non-Coding RNA SLC25A21-AS1 Promotes Multidrug Resistance in Nasopharyngeal Carcinoma by Regulating miR-324-3p/IL-6 Axis.

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