LINC00470 represses cell autophagy and cisplatin sensitivity of glioma via suppressing PTEN expression.

IF 1.5 4区 医学 Q4 NEUROSCIENCES Folia neuropathologica Pub Date : 2023-01-01 DOI:10.5114/fn.2023.125327
Biyin Chen, Wenwu Wang, Fangfeng Lin, Shuping Shi, Shunjie Ou, Yunqiu Yu
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Abstract

Introduction: Glioma is one of primary brain tumours which has the worst clinical prognoses of patients. As an alternative chemotherapeutic drug for malignant glioma, the therapeutic effect of cisplatin (CDDP) is devastatingly affected due to resistance in patients. In this study, we investigated the effect of LINC00470/PTEN on the CDDP sensitivity of glioma cells.

Material and methods: Differentially expressed lncRNAs and the downstream regulators in glioma tissue were obtained via bioinformatics analysis. LINC00470 and PTEN mRNA expression levels were detected using qRT-PCR. IC50 values of glioma cells were examined using Cell Counting Kit-8 (CCK-8). Cell apoptosis was revealed by flow cytometry. The expression level of autophagy-related protein was detected by western blot. Intracellular autophagosome formation was detected by immunofluorescence staining, and the methylation level of PTEN promoter was detected via methylation-specific PCR (MSP).

Results: Through the above steps, we found that LINC00470 was highly expressed in glioma cells, and the survival rate of patients was reduced in the presence of high expression of LINC00470. Silenced LINC00470 promoted LC3 II expression and autophagosome formation, and facilitated cell apoptosis to inhibit resistance to CDDP. While silenced PTEN could successfully reverse the previous effects on glioma cells.

Conclusions: Based on the above, LINC00470 repressed cell autophagy by constraining PTEN, thereby enhancing CDDP resistance of glioma cells.

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LINC00470通过抑制PTEN表达抑制胶质瘤细胞自噬和顺铂敏感性。
神经胶质瘤是临床预后最差的原发性脑肿瘤之一。顺铂(CDDP)作为恶性胶质瘤的替代化疗药物,由于患者的耐药,严重影响了其治疗效果。在本研究中,我们研究了LINC00470/PTEN对胶质瘤细胞CDDP敏感性的影响。材料与方法:通过生物信息学分析获得胶质瘤组织中差异表达的lncrna及其下游调控因子。采用qRT-PCR检测LINC00470和PTEN mRNA表达水平。使用细胞计数试剂盒-8 (CCK-8)检测胶质瘤细胞的IC50值。流式细胞术检测细胞凋亡情况。western blot检测自噬相关蛋白的表达水平。免疫荧光染色检测细胞内自噬体形成,甲基化特异性PCR (methyl- specific PCR, MSP)检测PTEN启动子甲基化水平。结果:通过以上步骤,我们发现LINC00470在胶质瘤细胞中高表达,并且在LINC00470高表达的情况下,患者的生存率降低。沉默的LINC00470可促进LC3 II的表达和自噬体的形成,促进细胞凋亡,从而抑制CDDP的耐药。而沉默的PTEN可以成功地逆转先前对胶质瘤细胞的影响。结论:综上所述,LINC00470通过抑制PTEN抑制细胞自噬,从而增强胶质瘤细胞对CDDP的抗性。
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来源期刊
Folia neuropathologica
Folia neuropathologica 医学-病理学
CiteScore
2.50
自引率
5.00%
发文量
38
审稿时长
>12 weeks
期刊介绍: Folia Neuropathologica is an official journal of the Mossakowski Medical Research Centre Polish Academy of Sciences and the Polish Association of Neuropathologists. The journal publishes original articles and reviews that deal with all aspects of clinical and experimental neuropathology and related fields of neuroscience research. The scope of journal includes surgical and experimental pathomorphology, ultrastructure, immunohistochemistry, biochemistry and molecular biology of the nervous tissue. Papers on surgical neuropathology and neuroimaging are also welcome. The reports in other fields relevant to the understanding of human neuropathology might be considered.
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