Zhao Qiwu, Li Haosheng, Li Wenchang, Guo Zichao, Jia Wenqing, Xu Shuiyu, Chen Sixia, Shen Xiaonan, Wang Changgang
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Interventional Radiography, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cell Dev Biol. 2023 Sep 6;11:1161667. doi: 10.3389/fcell.2023.1161667. eCollection 2023.
The expression characteristics of non-coding RNA (ncRNA) in colon adenocarcinoma (COAD) are involved in regulating various biological processes. To achieve these functions, ncRNA and a member of the Argonaute protein family form an RNA-induced silencing complex (RISC). The RISC is directed by ncRNA, especially microRNA (miRNA), to bind the target complementary mRNAs and regulate their expression by interfering with mRNA cleavage, degradation, or translation. However, how to identify potential miRNA biomarkers and therapeutic targets remains unclear. Here, we performed differential gene screening based on The Cancer Genome Atlas dataset and annotated meaningful differential genes to enrich related biological processes and regulatory cancer pathways. According to the overlap between the screened differential mRNAs and differential miRNAs, a prognosis model based on a least absolute shrinkage and selection operator-based Cox proportional hazards regression analysis can be established to obtain better prognosis characteristics. To further explore the therapeutic potential of miRNA as a target of mRNA intervention, we conducted an immunohistochemical analysis and evaluated the expression level in the tissue microarray of 100 colorectal cancer patients. The results demonstrated that the expression level of POU4F1, DNASE1L2, and WDR72 in the signature was significantly upregulated in COAD and correlated with poor prognosis. Establishing a prognostic signature based on miRNA target genes will help elucidate the molecular pathogenesis of COAD and provide novel potential targets for RNA therapy.
非编码RNA(ncRNA)在结肠腺癌(COAD)中的表达特征参与调控多种生物学过程。为实现这些功能,ncRNA与AGO蛋白家族成员形成RNA诱导沉默复合体(RISC)。RISC由ncRNA(尤其是微小RNA,即miRNA)引导,结合靶标互补mRNA,并通过干扰mRNA的切割、降解或翻译来调控其表达。然而,如何识别潜在的miRNA生物标志物和治疗靶点仍不清楚。在此,我们基于癌症基因组图谱数据集进行差异基因筛选,并对有意义的差异基因进行注释,以富集相关生物学过程和调控癌症途径。根据筛选出的差异mRNA与差异miRNA之间的重叠情况,可建立基于最小绝对收缩和选择算子的Cox比例风险回归分析的预后模型,以获得更好的预后特征。为进一步探索miRNA作为mRNA干预靶点的治疗潜力,我们进行了免疫组化分析,并评估了100例结直肠癌患者组织芯片中的表达水平。结果表明,该特征中POU4F1、DNASE1L2和WDR72的表达水平在COAD中显著上调,且与预后不良相关。基于miRNA靶基因建立预后特征将有助于阐明COAD的分子发病机制,并为RNA治疗提供新的潜在靶点。