Sun Mingming, Wang Yahui, Yang Huiju, Wang Xiaopeng, Su Lianlin, Yan Shuai
Department of Anorectal Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, China.
Department of Colorectal Surgery, The Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China.
Genet Test Mol Biomarkers. 2025 Apr;29(4):102-119. doi: 10.1089/gtmb.2024.0472. Epub 2025 Apr 15.
Slow transit constipation (STC) is a complication of depression that can negatively impact patient prognosis and quality of life. Nonetheless, the pathogenesis of STC is unclear. In this work, colon tissues from STC and non-STC patients were utilized to determine transcriptome expression patterns (messenger ribonucleic acids [mRNAs], Long noncoding RNAs [lncRNAs], and Circular RNAs [circRNAs]) via high-throughput sequencing. We found that 4430 mRNAs, 984 lncRNAs, and 2152 circRNAs exhibited substantial variations in expression patterns in the colon tissues of STC and non-STC patients. Next, we constructed a protein-protein interaction network and identified three significant elements, namely, POLR2B, SRSF1, and SUMO1, which attracted our interest. Utilizing the data of 6 upregulated circRNAs and 10 downregulated circRNAs, we created a competing endogenous RNA network. Subsequently, we found that hsa_circ_0000994 and hsa_circ_0008699 were significantly enriched in the upregulated and downregulated networks, respectively. The coexpression network analysis suggested that circRNAs and lncRNAs might exert control over mRNAs by influencing the neural functions of STC. According to the results of the integrated circRNA-miRNA-mRNA network, circRNA-regulated mRNAs were linked to both the transforming growth factor-β (TGF-β) and Notch signaling pathways. Our findings could provide new perspectives for identifying potential prognostic markers in STC. Targeting SUMO1 may present a promising approach to address colonic motility disorders in STC therapy.
慢传输型便秘(STC)是抑郁症的一种并发症,会对患者的预后和生活质量产生负面影响。然而,STC的发病机制尚不清楚。在这项研究中,我们利用STC患者和非STC患者的结肠组织,通过高通量测序来确定转录组表达模式(信使核糖核酸[mRNAs]、长链非编码RNA[lncRNAs]和环状RNA[circRNAs])。我们发现,4430种mRNAs、984种lncRNAs和2152种circRNAs在STC患者和非STC患者的结肠组织中表现出显著的表达模式差异。接下来,我们构建了一个蛋白质-蛋白质相互作用网络,并确定了三个重要元素,即POLR2B、SRSF1和SUMO1,这引起了我们的兴趣。利用6种上调的circRNAs和10种下调的circRNAs的数据,我们创建了一个竞争性内源性RNA网络。随后,我们发现hsa_circ_0000994和hsa_circ_0008699分别在上调和下调网络中显著富集。共表达网络分析表明,circRNAs和lncRNAs可能通过影响STC的神经功能来调控mRNAs。根据整合的circRNA-miRNA-mRNA网络结果,circRNA调控的mRNAs与转化生长因子-β(TGF-β)和Notch信号通路均有关联。我们的研究结果可为识别STC潜在的预后标志物提供新的视角。靶向SUMO1可能是解决STC治疗中结肠动力障碍的一种有前景的方法。