Zhang Xiaoting, Li Xiaofeng, Fu Xian, Yu Mengli, Qin Guicheng, Chen Guihong, Huang Chenchen
Shenzhen Bao'an District Songgang People's Hospital, Shenzhen, China.
Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China.
Front Oncol. 2021 Jul 12;11:643362. doi: 10.3389/fonc.2021.643362. eCollection 2021.
Bladder cancer (Bca) is the most common malignant tumor of the urinary system. Circular RNAs (circRNAs) have been recognized as key regulators in tumorigenesis. However, the molecular mechanisms underlying circRNAs involved in the progression of BCa remain largely unknown.
We detected the expression level of circular RNA TAF4B (circTAF4B) by qRT-PCR assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Wound healing and Transwell assays were performed to measure cell migration and invasion capability. Moreover, we performed qRT-PCR and western blotting assays to determine the expression levels of epithelial-mesenchymal transition (EMT) markers. A nuclear/cytoplasmic fractionation assay was used to measure the subcellular location of circTAF4B. RNA pull-down and dual-luciferase reporter assays were used to detect the target microRNA of circTAF4B. A mouse xenograft model was produced to analyze the effect of circTAF4B on the tumorigenesis of BCa.
In this study, we identified a novel circular RNA, circTAF4B, that is significantly upregulated in BCa and correlated with poor prognosis. Downregulated circTAF4B abolished the growth, metastasis and EMT process in BCa cells. Mechanistically, we found that circTAF4B facilitated the expression of transforming growth factor A (TGFA) by sponging miR-1298-5p. Finally, circTAF4B enhanced the proliferation and EMT process of BCa cells .
In summary, our study demonstrated that circTAF4B played a carcinogenic role in the growth, metastasis, and EMT process of BCa by regulating the miR-1298-5p/TGFA axis. Thus, circTAF4B may become a diagnostic and therapeutic target for BCa.
膀胱癌（Bca）是泌尿系统最常见的恶性肿瘤。环状RNA（circRNAs）已被认为是肿瘤发生过程中的关键调节因子。然而，circRNAs参与膀胱癌进展的分子机制仍 largely未知。
我们通过qRT-PCR检测环状RNA TAF4B（circTAF4B）的表达水平。通过CCK-8和集落形成试验评估细胞增殖。进行伤口愈合和Transwell试验以测量细胞迁移和侵袭能力。此外，我们进行qRT-PCR和蛋白质印迹试验以确定上皮-间质转化（EMT）标志物的表达水平。使用核/质分级分离试验测量circTAF4B的亚细胞定位。使用RNA下拉和双荧光素酶报告试验检测circTAF4B的靶微小RNA。建立小鼠异种移植模型以分析circTAF4B对膀胱癌肿瘤发生的影响。
在本研究中，我们鉴定了一种新型环状RNA，circTAF4B，其在膀胱癌中显著上调且与不良预后相关。下调circTAF4B消除了膀胱癌细胞的生长、转移和EMT过程。机制上，我们发现circTAF4B通过海绵化miR-1298-5p促进转化生长因子A（TGFA）的表达。最后，circTAF4B增强了膀胱癌细胞的增殖和EMT过程。
总之，我们的研究表明circTAF4B通过调节miR-1298-5p/TGFA轴在膀胱癌的生长、转移和EMT过程中发挥致癌作用。因此，circTAF4B可能成为膀胱癌的诊断和治疗靶点。
