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锌指蛋白家族成员2反义RNA1(ZFPM2-AS1)通过JAK-STAT和AKT信号通路促进人非小细胞肺癌细胞的增殖、迁移和侵袭。

ZFPM2-AS1 promotes the proliferation, migration, and invasion of human non-small cell lung cancer cells involving the JAK-STAT and AKT pathways.

作者信息

Wang Xiwen, Tang Jun, Zhao Jungang, Lou Bin, Li Li

机构信息

Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Department of Hygiene Toxicology, School of Public Health, China Medical University, Shenyang, Liaoning, China.

出版信息

PeerJ. 2020 Oct 26;8:e10225. doi: 10.7717/peerj.10225. eCollection 2020.

Abstract

PURPOSE

Recent studies have determined that long non-coding RNAs (lncRNAs) are potential prognostic biomarkers for non-small cell lung cancers (NSCLCs). The purpose of this study was to analyze the function and associated pathways of zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) in NSCLC cells.

METHODS

We used qRT-PCR to analyze ZFPM2-AS1's transcription level. Its proliferation, migration, and invasion capacities were determined using MTT, colony forming, wound healing, and transwell assays. We additionally analyzed the correlation between ZFPM2 and immune infiltration using the Tumor Immune Estimation Resource (TIMER) database, and the protein expression levels using Western blots.

RESULTS

We found that ZFPM2-AS1 expression in NSCLC specimens and cell lines was elevated compared to the control group. ZFPM2-AS1 is an oncogene and independent prognostic predictor of poor survival in NSCLCs, and its expression had a positive correlation with tumor size and lymph node metastasis in our clinical data. MTT, colony forming, wound healing, and transwell assays showed a positive correlation between ZFPM2-AS1 expression and the proliferation, migration, and invasion of NSCLC cells in the presence and absence of interferon- (IFN-). Using the TIMER database, we hypothesized that ZFPM2 was negatively correlated with ZFPM2-AS1 expression, as well as the immune infiltration levels in lung adenocarcinoma (LUAD). Finally, we found that ZFPM2-AS1 negatively regulated ZFPM2 expression, and had a positive correlation with PD-L1 expression through the JAK-STAT and AKT pathways.

CONCLUSION

Our study confirmed that ZFPM2-AS1 promotes the proliferation, migration, and invasion of NSCLC cells via the JAK-STAT and AKT pathways. Further research on the ZFPM2-AS1 pathway regulation mechanism is needed.

摘要

目的

近期研究已确定长链非编码RNA(lncRNAs)是非小细胞肺癌(NSCLCs)潜在的预后生物标志物。本研究旨在分析锌指蛋白多型2反义RNA 1(ZFPM2-AS1)在NSCLC细胞中的功能及相关通路。

方法

我们采用qRT-PCR分析ZFPM2-AS1的转录水平。通过MTT、集落形成、伤口愈合和Transwell实验测定其增殖、迁移和侵袭能力。我们还使用肿瘤免疫评估资源(TIMER)数据库分析ZFPM2与免疫浸润之间的相关性,并通过蛋白质印迹法分析蛋白质表达水平。

结果

我们发现与对照组相比,NSCLC标本和细胞系中ZFPM2-AS1的表达升高。ZFPM2-AS1是一种癌基因,是NSCLCs患者生存预后不良的独立预测指标,在我们的临床数据中其表达与肿瘤大小和淋巴结转移呈正相关。MTT、集落形成、伤口愈合和Transwell实验表明,在有或无干扰素-(IFN-)的情况下,ZFPM2-AS1表达与NSCLC细胞的增殖、迁移和侵袭呈正相关。使用TIMER数据库,我们推测ZFPM2与ZFPM2-AS1表达以及肺腺癌(LUAD)中的免疫浸润水平呈负相关。最后,我们发现ZFPM2-AS1负向调节ZFPM2表达,并通过JAK-STAT和AKT通路与PD-L1表达呈正相关。

结论

我们的研究证实ZFPM2-AS1通过JAK-STAT和AKT通路促进NSCLC细胞的增殖、迁移和侵袭。需要对ZFPM2-AS1通路调控机制进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d8/7594634/8c4d9d154741/peerj-08-10225-g001.jpg

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