Che Wenan, Ye Shanting, Cai Aoxiang, Cui Xiaojuan, Sun Yuandong
Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization, School of Life Sciences, Hunan University of Science and Technology, Xiangtan, China.
Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
Front Mol Biosci. 2020 Nov 17;7:607740. doi: 10.3389/fmolb.2020.607740. eCollection 2020.
Enhancers are cis-acting elements that can promote the expression of target genes and respond to estrogen to induce the transcription of eRNAs, which are closely associated with cancer development. Further study on eRNAs may lead to a better understanding of the significance of transcriptional regulation and the progression of malignant tumors. SMAD7 enhancer RNA (SMAD7e) is an estrogen-responsive eRNA. However, the relationship between SMAD7e and bladder cancer remains unclear. SMAD7e was significantly upregulated in bladder cancer tissues and estrogen-stimulated cells. Knockdown of SMAD7e by CRISPR-Cas13a suppressed cell proliferation and migration, and induced cell apoptosis and inhibited cell invasion. Estrogen caused overexpression of SMAD7e and played a facilitating role in bladder cancer cells. Furthermore, knockdown of SMAD7e by CRISPR-Cas13a prevented the cancer-promoting effects of estrogen on bladder cancer both and . The present study suggested the crucial role of SMAD7e in bladder cancer. Estrogen might promote the development of bladder cancer by inducing SMAD7e production. These findings may provide a potential target for CRISPR-mediated gene therapy for bladder cancer in the future.
增强子是一种顺式作用元件，可促进靶基因的表达并对雌激素作出反应，从而诱导与癌症发展密切相关的eRNA转录。对eRNA的进一步研究可能有助于更好地理解转录调控的意义以及恶性肿瘤的进展。SMAD7增强子RNA（SMAD7e）是一种雌激素反应性eRNA。然而，SMAD7e与膀胱癌之间的关系仍不清楚。SMAD7e在膀胱癌组织和雌激素刺激的细胞中显著上调。通过CRISPR-Cas13a敲低SMAD7e可抑制细胞增殖和迁移，并诱导细胞凋亡和抑制细胞侵袭。雌激素导致SMAD7e过表达，并在膀胱癌细胞中发挥促进作用。此外，通过CRISPR-Cas13a敲低SMAD7e可在体内和体外阻止雌激素对膀胱癌的促癌作用。本研究表明SMAD7e在膀胱癌中起关键作用。雌激素可能通过诱导SMAD7e产生来促进膀胱癌的发展。这些发现可能为未来CRISPR介导的膀胱癌基因治疗提供潜在靶点。
