Department of Oncology and The Key Laboratory of Cancer Molecular and Translational Research, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong, P.R. China.
Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 262000, P.R. China.
Curr Stem Cell Res Ther. 2023;18(1):105-114. doi: 10.2174/1574888X17666220331124607.
Diabetes mellitus (DM) is among the most common chronic diseases, and diabetic enteropathy (DE), which is a complication caused by DM, is a serious health condition. Long noncoding RNAs (lncRNAs) are regulators of DE progression.
However, the mechanisms of action of multiple lncRNAs involved in DE remain poorly understood.
Reverse transcription-quantitative PCR (RT-qPCR) and in situ hybridization were used to analyze terminal differentiation-induced lncRNA (Tincr) expression in intestinal epithelial cells (IECs) in the DM state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays were used to identify the genes targeted by Tincr. The role of miR-668-3p was then explored by up- and down-regulating its expression in vitro and in vivo.
In this study, we observed that the level of lncRNA Tincr was increased in IECs in the DM state. More importantly, Tincr was associated with abnormal intestinal epithelial stem cell (IESC) differentiation in DM. Our mechanistic study demonstrated that Tincr is a major marker of Lgr5+ stem cells in DM. In addition, we investigated whether Tincr directly targets miR-668-3p and whether miR-668-3p targets Klf3. Our findings showed that Tincr sponged miR-668-3p, which attenuated abnormal IESC differentiation in DM by regulating Klf3 expression.
This study presents evidence of an essential role for Tincr in IESC differentiation in DM.
糖尿病（DM）是最常见的慢性疾病之一，而由 DM 引起的糖尿病肠病（DE）是一种严重的健康状况。长链非编码 RNA（lncRNA）是 DE 进展的调节剂。
然而，多种参与 DE 的 lncRNA 的作用机制仍知之甚少。
采用逆转录定量 PCR（RT-qPCR）和原位杂交分析 DM 状态下肠上皮细胞（IEC）中诱导末端分化的 lncRNA（Tincr）的表达。采用微阵列分析、生物信息学分析和荧光素酶报告基因测定鉴定 Tincr 靶向的基因。然后通过体外和体内上调和下调 miR-668-3p 的表达来探索 miR-668-3p 的作用。
在这项研究中，我们观察到 lncRNA Tincr 在 DM 状态下的 IEC 中表达增加。更重要的是，Tincr 与 DM 中异常的肠上皮干细胞（IESC）分化有关。我们的机制研究表明，Tincr 是 DM 中 Lgr5+干细胞的主要标志物。此外，我们研究了 Tincr 是否直接靶向 miR-668-3p，以及 miR-668-3p 是否靶向 Klf3。我们的研究结果表明，Tincr 作为 miR-668-3p 的海绵分子，通过调节 Klf3 的表达，减弱 DM 中异常的 IESC 分化。
本研究证明了 Tincr 在 DM 中 IESC 分化中的重要作用。
