Dysregulated circular RNAs (circRNAs) contribute to tumourigenesis and cancer progression. However, the expression patterns and biological functions of circRNAs in colorectal cancer (CRC) remain elusive. Here, RNA sequencing and bioinformatics analyses are applied to screen for aberrantly expressed circRNAs. The expression of circFBXW4 in CRC tissues and cell lines is determined by quantitative real-time PCR. A series of in vitro and in vivo biological function assays are implemented to assess the functions of circFBXW4. The regulatory mechanisms linking circFBXW4, miR-338-5p, and SLC5A7 are explored by western blotting, dual luciferase reporter assays, and RNA pull-down assays. CircFBXW4 is dramatically downregulated in CRC tissues and cell lines. circFBXW4 downregulation is clearly correlated with malignant features and patient overall survival in CRC. Functionally, ectopic expression of circFBXW4 strikingly impairs the proliferation, migration, and invasion capacities of CRC cells in vitro and in vivo, whereas circFBXW4 knockdown has the opposite effects. Mechanistically, circFBXW4 competitively binds to miR-338-5p and prevents it from interacting with and repressing its target SLC5A7, thus suppressing the progression of CRC. This study reveals the specific critical role of circFBXW4 in inhibiting CRC progression via the miR-338-5p/SLC5A7 axis and provides an additional target for eradicating CRC.
目的 开发基于免疫相关基因(immune-related genes,IRGs)的预后风险的预测标志物并评估其在结肠癌患者预后预测中的价值.方法 从TCGA数据库中收集452例结肠癌患者的基因芯片数据集,从ImmPort数据库中获得2498个IRGs数据集,取交集后采用单因素和多因素Cox比例风险回归分析,筛选并构建IRGs基因模型.为评估基因模型预测预后的价值,采用Cox比例风险回归分析IRGs模型、临床病理特征与结肠癌患者预后的相关性,并分析风险评分与免疫细胞浸润的关系.结果 在结肠癌组织中共确定了206个差异表达的IRGs,经过单因素和多因素Cox比例风险回归分析,确定了11个IRGs标志物,即溶质载体家族10成员2(SLC10A2)、C-X-C基序趋化因子配体5(CXCL5)、C-C基序趋化因子配体(CCL28)、免疫球蛋白kappa变量1D-42 (IGKV1D-42)、嗜铬粒蛋白A(CHGA)、内皮细胞特异性分子1(ESM1)、胃泌激素释放肽(GRP)、斯钙素2抗体(STC2)、尿皮质素(UCN)、催产素受体(OXTR)和免疫球蛋白重常数Y 1(IGHGl).根据IRGs风险标志物的风险值的中位数将结肠癌患者分为高风险组和低风险组,高风险组患者的总生存时间(OS)差于低风险组患者(P<0.001).时间依赖的ROC曲线下面积(AUC)为0.754,提示IRGs模型对结肠癌患者预后有较好的预测能力.IRGs风险评分高,则结肠癌T分期晚(T3~T4),淋巴结转移多(N1~ N2)及临床分期晚(Ⅲ~Ⅳ),P<0.05.除中性粒细胞外,B细胞、CD4+T细胞、CD8+T细胞、树突状细胞和巨噬细胞浸润密度随风险值评分增高而增高(p<0.05).结论 本研究筛选的11个IRGs基因模型,其风险值可用于预测结肠癌患者的预后,并可作为评估结肠癌预后的生物标志物.
Background Although numerous studies demonstrate the role of cancer stem cells in occurrence, recurrence, and distant metastases in gastric cancer (GC), little is known about the evolving genetic and epigenetic changes in the stem and progenitor cells. The purpose of this study was to identify the stem cell subtypes in GC and examine their clinical relevance. Methods Two publicly available datasets were used to identify GC stem cell subtypes, and consensus clustering was performed by unsupervised machine learning methods. The cancer stem cell (CSC) typing-related risk scoring (RS) model was established through multivariate Cox regression analysis. Results Cross-platform dataset-based two stable GC stem cell subtypes, namely low stem cell enrichment (SCE_L) and high stem cell enrichment (SCE_H), were prudently identified. Gene set enrichment analysis revealed that the classical oncogenic pathways, immune-related pathways, and regulation of stem cell division were active in SCE_H; ferroptosis, NK cell activation, and post-mutation repair pathways were active in SCE_L. GC stem cell subtypes could accurately predict clinical outcomes in patients, tumor microenvironment cell-infiltration characteristics, somatic mutation landscape, and potential responses to immunotherapy, targeted therapy, and chemotherapy. Additionally, a CSC typing-related RS model was established; it was strongly independent and could accurately predict the patient’s overall survival. Conclusions This study demonstrated the complex oncogenic mechanisms underlying GC. The findings provide a basis and reference for the diagnosis and treatment of GC.
The real-time and intelligent space-based information service system is a next-generation space-based information system featuring multi-satellite coordination and multi-network interconnection. It will be widely used in satellite communications, navigation, and remote sensing. To support the top-level design and construction of the real-time and intelligent space-based information service system, this paper studies the modeling simulation and performance evaluation of the system, and analyzes the necessity, requirements, and development trends of system simulation and evaluation. The key technologies such as scalable and efficient distributed simulation, spatial-temporal dynamic evaluation, and systematic modeling are discussed, considering the characteristics of the system, such as dynamic time-varying, diverse business, and heterogeneity. Based on the design of the distributed simulation and evaluation system, the transmission support capabilities of different low-orbit communication satellite systems are compared and evaluated, taking high-resolution remote sensing as an example. The results show that during the remote sensing data transmission process, the OneWeb satellite constellation has smaller delay, less packet loss, and higher capacity and stability, owing to its dense coverage; however, its capacity per satellite is inferior to that of the Hongyun satellite constellation which has a smaller coverage density. This study can provide technical supports for the feasibility evaluation and construction of the real-time and intelligent space-based information service system.
Compared to common data presentation methods such as tables and diagrams, thematic maps have the advantage of directly presenting complex, multidimensional spatial data. In this study, over 500 thematic maps are planned that present pesticide residue data from the inspection of fruit and vegetable samples. The data contain information on the samples, pesticides, sampling locations, maximum residue limits and inspection. Different calculation strategies are used to transform the original data into highly integrated data for cartography based on the demand investigation. During the map design process, standardized design should be used to ensure rigorous and consistent display of cartographic symbols. Two of the maps are used as examples to explain the data processing and map design procedures. The process can be used on all maps in this study and on more complex data.