LINC02154通过增强SPC24启动子活性和激活PI3K-AKT信号通路促进肝癌的增殖和转移

IF 4.8 2区医学 Q1 Medicine Cellular Oncology Pub Date : 2022-06-01 Epub Date: 2022-05-11 DOI:10.1007/s13402-022-00676-7

Huan Yue, Kaifeng Wu, Kanglin Liu, Luxia Gou, Ailong Huang, Hua Tang

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引用次数: 0

摘要

背景：长链非编码rna （lncRNAs）的异常表达与肝细胞癌的发生和进展有关，但到目前为止，Linc02154在HCC中的临床病理意义和潜在作用仍有待确定。在这里，我们的目的是研究Linc02154在HCC中的潜在作用和作用方式。方法：采用qRT-PCR检测20对HCC/正常组织和7株HCC细胞系中Linc02154的表达。采用荧光原位杂交法和核浆分离法检测Linc02154在HCC细胞中的定位。通过MTS、EdU结合、集落形成、流式细胞术、划伤愈合和transwell实验评估Linc02154在体外肝癌细胞增殖、迁移和侵袭中的作用，并通过BALB/c裸鼠异种移植评估其在体内的作用。采用RNA测序和Western blotting技术评价Linc02154对SPC24基因表达的调控作用。双荧光素酶报告试验用于评估Linc02154与SPC24启动子的推测相互作用。结果：我们发现了一种新的lncRNA， Linc02154，它在总生存率较低的HCC细胞和组织中高表达。功能实验显示，外源Linc02154在MHCC-97H和SK-Hep1细胞中的表达促进了它们在体外的增殖、迁移和侵袭以及体内的肿瘤发生。通过双荧光素酶报告基因实验，我们发现Linc02154可以增强SPC24启动子（-500 bp ~ -1000区域）的活性。外源性过表达Linc02154通过激活PI3K/AKT及其下游信号，包括细胞周期进程和emt相关基因表达，导致SPC24上调。结论：我们的数据表明Linc02154可能作为HCC的一种有价值的生物标志物和潜在的治疗靶点。

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LINC02154 promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing SPC24 promoter activity and activating the PI3K-AKT signaling pathway.

Background: Abnormal expression of long non-coding RNAs (lncRNAs) has been associated with the initiation and progression of hepatocellular carcinoma but, as yet, the clinicopathologic significance and potential role of Linc02154 in HCC remains to be determined. Here, we aimed to investigate the potential role and mode of action of Linc02154 in HCC.

Methods: The expression of Linc02154 in 20 pairs of HCC/normal tissues and 7 HCC cell lines was detected by qRT-PCR. The localization of Linc02154 in HCC cells was detected using fluorescence in situ hybridization and nuclear-plasma separation assays. MTS, EdU incorporation, colony formation, flow cytometry, scratch wound-healing and transwell assays were performed to assess the role of Linc02154 in HCC cell proliferation, migration and invasion in vitro, and BALB/c nude mice xenografts were used to evaluate its role in vivo. RNA sequencing and Western blotting were used to evaluate the regulatory effect of Linc02154 on SPC24 gene expression. A dual-luciferase reporter assay was used to assess a putative interaction of Linc02154 with the SPC24 promoter.

Results: We identified a new lncRNA, Linc02154, that is highly expressed in HCC cells and tissues of patients with a poor overall survival. Functional experiments revealed that exogenous Linc02154 expression in MHCC-97H and SK-Hep1 cells promoted their proliferation, migration and invasion in vitro and their tumorigenesis in vivo. Using a dual luciferase reporter assay we found that Linc02154 can enhance SPC24 promoter (-500 bp ~ -1000 region) activity. Exogenous over-expression of Linc02154 led to up-regulation of SPC24 by activating PI3K/AKT and its downstream signals, including cell cycle progression and EMT-associated gene expression.

Conclusion: Our data suggest that Linc02154 may serve as a valuable biomarker of HCC and as a potential therapeutic target.

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来源期刊

Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

10.40

自引率

1.50%

发文量

审稿时长

16 weeks

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.