College of Life Science & Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, P.R. China;
College of Life Science & Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, P.R. China.
Cancer Genomics Proteomics. 2023 Jul-Aug;20(4):383-397. doi: 10.21873/cgp.20390.
BACKGROUND/AIM: Cervical cancer (CC) is a high-risk disease in women, and advanced CC can be difficult to treat even with surgery, radiotherapy, and chemotherapy. Hence, developing more effective treatment methods is imperative. Cancer cells undergo a renewal process to escape immune surveillance and then attack the immune system. However, the underlying mechanisms remain unclear. Currently, only one immunotherapy drug has been approved by the Food and Drug Administration for CC, thus indicating the need for and importance of identifying key targets related to immunotherapy.
Data on CC and normal cervical tissue samples were downloaded from the National Center for Biotechnology Information database. Transcriptome Analysis Console software was used to analyze differentially expressed genes (DEGs) in two sample groups. These DEGs were uploaded to the DAVID online analysis platform to analyze biological processes for which they were enriched. Finally, Cytoscape was used to map protein interaction and hub gene analyses.
A total of 165 up-regulated and 362 down-regulated genes were identified. Among them, 13 hub genes were analyzed in a protein-protein interaction network using the Cytoscape software. The genes were screened out based on the betweenness centrality value and average degree of all nodes. The hub genes were as follows: ANXA1, APOE, AR, C1QC, CALML5, CD47, CTSZ, HSP90AA1, HSP90B1, NOD2, THY1, TLR4, and VIM. We identified the following 12 microRNAs (miRNAs) that target the hub genes: hsa-miR-2110, hsa-miR-92a-2-5p, hsa-miR-520d-5p, hsa-miR-4514, hsa-miR-4692, hsa-miR-499b-5p, hsa-miR-5011-5p, hsa-miR-6847-5p, hsa-miR-8054, hsa-miR-642a-5p, hsa-miR-940, and hsa-miR-6893-5p.
Using bioinformatics, we identified potential miRNAs that regulated the cancer-related genes and long noncoding RNAs (lncRNAs) that regulated these miRNAs. We further elucidated the mutual regulation of mRNAs, miRNAs, and lncRNAs involved in CC occurrence and development. These findings may have major applications in the treatment of CC by immunotherapy and the development of drugs against CC.
背景/目的：宫颈癌（CC）是女性的一种高危疾病，即使采用手术、放疗和化疗，晚期 CC 也难以治疗。因此，开发更有效的治疗方法势在必行。癌细胞通过更新过程逃避免疫监视，然后攻击免疫系统。然而，其潜在机制尚不清楚。目前，美国食品和药物管理局仅批准了一种免疫疗法药物用于 CC，这表明需要并重视确定与免疫疗法相关的关键靶标。
从国家生物技术信息中心数据库下载 CC 和正常宫颈组织样本的数据。使用转录组分析控制台软件分析两组样本中的差异表达基因（DEGs）。将这些 DEGs 上传至 DAVID 在线分析平台，以分析其富集的生物过程。最后，使用 Cytoscape 绘制蛋白质相互作用和枢纽基因分析图。
共鉴定出 165 个上调和 362 个下调基因。其中，使用 Cytoscape 软件对蛋白质-蛋白质相互作用网络中的 13 个枢纽基因进行了分析。根据所有节点的介数中心度值和平均度筛选出这些基因。枢纽基因如下：ANXA1、APOE、AR、C1QC、CALML5、CD47、CTSZ、HSP90AA1、HSP90B1、NOD2、THY1、TLR4 和 VIM。我们鉴定出针对这些枢纽基因的以下 12 个 microRNAs（miRNAs）：hsa-miR-2110、hsa-miR-92a-2-5p、hsa-miR-520d-5p、hsa-miR-4514、hsa-miR-4692、hsa-miR-499b-5p、hsa-miR-5011-5p、hsa-miR-6847-5p、hsa-miR-8054、hsa-miR-642a-5p、hsa-miR-940 和 hsa-miR-6893-5p。
通过生物信息学，我们鉴定出可能调节癌症相关基因的 miRNA 和可能调节这些 miRNA 的长链非编码 RNA（lncRNA）。我们进一步阐明了参与 CC 发生和发展的 mRNA、miRNA 和 lncRNA 之间的相互调节。这些发现可能在 CC 的免疫治疗和 CC 药物的开发方面具有重要的应用价值。
