Identification and verification of HCAR3 and INSL5 as new potential therapeutic targets of colorectal cancer.
Identification and verification of HCAR3 and INSL5 as new potential therapeutic targets of colorectal cancer.
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HCAR3和INSL5作为结直肠癌潜在治疗新靶点的鉴定和验证
DOI：
10.1186/s12957-021-02335-x
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发表时间：
2021-08-21
影响因子：
3.2
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Yang X;Wei W;Tan S;Guo L;Qiao S;Yao B;Wang Z
结直肠癌（CRC）是最常见的胃肠道癌症之一，在全球癌症相关死亡中排名第三。本研究旨在通过生物信息学分析，发现与CRC发病机制相关的新型生物标志物，并进一步验证临床肿瘤样本和CRC细胞系中的生物标志物。方法利用NCBI-GEO数据集进行一系列生物信息学分析，并构建蛋白相互作用（PPI）网络。该分析鉴定出Hub基因，并在the Cancer Genome Atlas （TCGA）结肠癌和直肠癌（COADREAD）数据库中探索结直肠癌患者mRNA表达和总生存率的数据分布。此外，通过Real-time定量PCR分析、western blotting分析和免疫组织化学分析，验证了HCAR3和INLS5在临床肿瘤样本中的差异表达。最后，构建过表达INSL5的CRC细胞，并将其用于CCK8、细胞周期和细胞凋亡的体外验证实验。结果共筛选到286个差异表达基因（deg），其中在2个CRC数据库中表达升高的基因64个，表达降低的基因143个，从中鉴定出10个关键基因：CXCL1、HCAR3、CXCL6、CXCL8、CXCL2、CXCL5、PPY、SST、INSL5和npy1r。在这些基因中，hcar3和insl5此前未被探索，并在体外进一步验证。结论shcar3在结直肠癌组织中表达较高，与结直肠癌患者的总生存率较高相关。INSL5在正常组织中的表达高于肿瘤组织，其高表达与结直肠癌预后较好相关。过表达INSL5显著抑制结直肠癌细胞的增殖，促进PARP的剪切。这项综合生物信息学研究提出了10个与结直肠癌相关的关键枢纽基因。hcar3和insl5在肿瘤组织中表达，它们与较差的生存率相关，值得进一步研究作为潜在的治疗靶点。
BackgroundColorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and ranks third in cancer-related deaths worldwide. This study was conducted to identify novel biomarkers related to the pathogenesis of CRC based upon a bioinformatics analysis, and further verify the biomarkers in clinical tumor samples and CRC cell lines.MethodsA series of bioinformatics analyses were performed using datasets from NCBI-GEO and constructed a protein–protein interaction (PPI) network. This analysis enabled the identification of Hub genes, for which the mRNA expression and overall survival of CRC patients data distribution was explored in The Cancer Genome Atlas (TCGA) colon cancer and rectal cancer (COADREAD) database. Furthermore, the differential expression of HCAR3 and INLS5 was validated in clinical tumor samples by Real-time quantitative PCR analysis, western blotting analysis, and immunohistochemistry analysis. Finally, CRC cells over-expressing INSL5 were constructed and used for CCK8, cell cycle, and cell apoptosis validation assays in vitro.ResultsA total of 286 differentially expressed genes (DEGs) were screened, including 64 genes with increased expression and 143 genes with decreased expression in 2 CRC database, from which 10 key genes were identified:CXCL1,HCAR3,CXCL6,CXCL8,CXCL2,CXCL5,PPY,SST,INSL5, andNPY1R.Among these genes,HCAR3andINSL5had not previously been explored and were further verified in vitro.ConclusionsHCAR3 expression was higher in CRC tissues and associated with better overall survival of CRC patients. INSL5 expression in normal tissue was higher than that in tumor tissue and its high expression was associated with a better prognosis for CRC. The overexpression of INSL5 significantly inhibited the proliferation and promoted the shearing of PARP of CRC cells.This integrated bioinformatics study presented 10 key hub genes associated with CRC.HCAR3andINSL5were expressed in tumor tissue and these were associated with poor survival and warrant further studies as potential therapeutic targets.
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DOI：
10.1109/tvcg.2014.2346248
发表时间：
2014-12
影响因子：
5.2
作者：
Lex A;Gehlenborg N;Strobelt H;Vuillemot R;Pfister H
通讯作者：
Pfister H
影响因子：
3.5
作者：
Chen, Linbo;Lu, Dewen;Xu, Feng
通讯作者：
Xu, Feng
影响因子：
4.8
作者：
Liu, CL;Chen, JC;Lovenberg, TW
通讯作者：
Lovenberg, TW
影响因子：
4.1
作者：
Luo, Xiao;Li, Ting;Wang, Ming-Wei
通讯作者：
Wang, Ming-Wei
影响因子：
3
作者：
Tseng, WW;Liu, CD
通讯作者：
Liu, CD