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基于生物网络分析指导的橙皮素处理肝癌细胞的转录组分析

Transcriptome analysis of sinensetin-treated liver cancer cells guided by biological network analysis.

作者信息

Kim Seong Min, Rampogu Shailima, Vetrivel Preethi, Kulkarni Apoorva M, Ha Sang Eun, Kim Hun Hwan, Lee Keun Woo, Kim Gon Sup

机构信息

Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam 52828, Republic of Korea.

Division of Life Science, Division of Applied Life Science (BK21 Plus), Plant Molecular Biology and Biotechnology Research Center, Research Institute of Natural Science, Gyeongsang National University, Jinju, Gyeongsangnam 52828, Republic of Korea.

出版信息

Oncol Lett. 2021 May;21(5):355. doi: 10.3892/ol.2021.12616. Epub 2021 Mar 4.

Abstract

Hepatocellular carcinoma is recognized as one of the most frequently occurring malignant types of liver cancer globally, making the identification of biomarkers critically important. The aim of the present study was to identify the genes involved in the anticancer effects of flavonoid compounds so that they may be used as targets for cancer treatment. Sinensetin (SIN), an isolated polymethoxyflavone monomer compound, possesses broad antitumor activities . Therefore, the identification of a transcriptome profile on the condition of cells treated with SIN may aid to better understand the genes involved and its mechanism of action. Genomic profiling studies of cancer are increasing rapidly in order to provide gene expression data that can reveal prognostic biomarkers to combat liver cancer. In the present study, high-throughput RNA sequencing (RNA-seq) was performed to reveal differential gene expression patterns between SIN-treated and SIN-untreated human liver cancer HepG2 cells. A total of 43 genes were identified to be differentially expressed (39 downregulated and 4 upregulated in the SIN-treated group compared with the SIN-untreated group). An extensive network analysis for these 43 genes resulted in the identification of 10 upregulated highly interconnected hub genes that contributed to the progression of cancer. Functional enrichment analysis of these 10 hub genes revealed their involvement in the regulation of apoptotic processes, immune response and tumor necrosis factor production. Additionally, the mRNA expression levels of these 10 genes were evaluated using reverse transcription-quantitative PCR, and the results were consistent with the RNA-seq data. Overall, the results of the present study revealed differentially expressed genes involved in cancer after SIN treatment in HepG2 cells and may help to develop strategies targeting these genes for treating liver cancer.

摘要

肝细胞癌被公认为全球最常见的肝癌恶性类型之一,因此识别生物标志物至关重要。本研究的目的是确定参与黄酮类化合物抗癌作用的基因,以便将其用作癌症治疗的靶点。川陈皮素(SIN)是一种分离出的多甲氧基黄酮单体化合物,具有广泛的抗肿瘤活性。因此,确定SIN处理细胞条件下的转录组图谱可能有助于更好地了解相关基因及其作用机制。为了提供能够揭示对抗肝癌预后生物标志物的基因表达数据,癌症的基因组分析研究正在迅速增加。在本研究中,进行了高通量RNA测序(RNA-seq)以揭示SIN处理组和未处理组的人肝癌HepG2细胞之间的差异基因表达模式。共鉴定出43个差异表达基因(与未处理组相比,处理组中有39个下调,4个上调)。对这43个基因进行广泛的网络分析,确定了10个上调的高度相互连接的枢纽基因,这些基因促进了癌症的进展。对这10个枢纽基因的功能富集分析表明它们参与了凋亡过程、免疫反应和肿瘤坏死因子产生的调节。此外,使用逆转录定量PCR评估了这10个基因的mRNA表达水平,结果与RNA-seq数据一致。总体而言,本研究结果揭示了HepG2细胞经SIN处理后参与癌症的差异表达基因,并可能有助于制定针对这些基因治疗肝癌的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf9/7968004/63f478e5258c/ol-21-05-12616-g00.jpg

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