Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Department of Colorectal and Anal Surgery, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou 434020, China.
Dis Markers. 2022 Jun 10;2022:3653363. doi: 10.1155/2022/3653363. eCollection 2022.
Slow transit constipation (STC) is a clinical syndrome characterized by a decreased urge to defecate and delayed colonic transit. Circular RNAs (circRNAs) are a recently discovered class of regulatory RNAs that have emerged as critical biomarkers and regulators of various diseases. However, the expression profiles and mechanisms underlying circRNA regulation in human STC tissues have not been explored.
High-throughput RNA sequencing technology was used to compare the differences in circRNA expression profiles in colon samples taken from patients with STC or controls. Bioinformatics analyses were performed on the host genes of the differentially expressed circRNAs (DE-circRNAs), a competing endogenous RNA network was constructed, and the expression levels of some DE-circRNAs were verified using quantitative real-time polymerase chain reactions (qRT-PCR).
There were 190 DE-circRNAs identified in the STC group. Bioinformatics analysis predicted that the DE-circRNAs were enriched in the relaxation of smooth muscle, actin binding, actin cytoskeleton organization, dilated cardiomyopathy, and cardiac muscle contraction. These results suggest that muscle diseases may be related to the pathogenesis of STC. The expression levels of the 12 most differentially expressed circRNAs were verified using qRT-PCR. In addition, circRNA-microRNA-mRNA regulatory networks were constructed using the 8 most significant circRNAs. Some mRNAs predicted to be closely related to smooth muscle function were found in these networks.
This study provides a helpful blueprint for researchers to select candidate circRNAs for further study of the pathogenesis of STC and screen potential biomarkers or targets for use in the diagnosis and treatment of STC.
慢传输型便秘（STC）是一种以排便欲望减弱和结肠传输延迟为特征的临床综合征。环状 RNA（circRNA）是一类新发现的调控 RNA，已成为多种疾病的关键生物标志物和调控因子。然而，人类 STC 组织中 circRNA 调控的表达谱和机制尚未得到探索。
采用高通量 RNA 测序技术比较 STC 患者和对照组结肠样本中 circRNA 表达谱的差异。对差异表达 circRNAs（DE-circRNAs）的宿主基因进行生物信息学分析，构建竞争性内源性 RNA 网络，并采用实时定量聚合酶链反应（qRT-PCR）验证部分 DE-circRNAs 的表达水平。
在 STC 组中鉴定出 190 个 DE-circRNAs。生物信息学分析预测 DE-circRNAs 富集于平滑肌松弛、肌动蛋白结合、肌动蛋白细胞骨架组织、扩张型心肌病和心肌收缩。这些结果提示肌肉疾病可能与 STC 的发病机制有关。采用 qRT-PCR 验证了 12 个差异表达最显著的 circRNAs 的表达水平。此外，还利用 8 个最显著的 circRNAs 构建了 circRNA-miRNA-mRNA 调控网络。在这些网络中发现了一些预测与平滑肌功能密切相关的 mRNAs。
本研究为研究人员提供了一个有价值的蓝图，有助于选择候选 circRNAs 进一步研究 STC 的发病机制，并筛选出用于 STC 诊断和治疗的潜在生物标志物或靶点。
