Mei Mei, Wang Yingjun, Song Wenting, Li Zhaoming, Wang Qilong, Li Jiayin, Zhang Mingzhi
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Νo. 1 Jianshe East Road, Zhengzhou, Henan, China.
The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Cancer Cell Int. 2021 Nov 4;21(1):594. doi: 10.1186/s12935-021-02296-x.
Natural killer/T-cell lymphoma (NKTCL) is a rare and aggressive subtype of Non-Hodgkin's Lymphoma. CircRNA has shown great potential to become a biomarker in plasma. In this study, we aimed to determine circRNA for its diagnostic and prognostic value and biological function in NKTCL.
The circRNA microarray of plasma from NKTCL patients and healthy donors were conducted. The relative expressions of target circRNA were verified by qRT-PCR. We conducted function experiments in vitro and in vivo. Bioinformatics predicted the target miRNA of the target circRNA and the binding site was detected by the dual luciferase report assay. Downstream target protein was predicted and detected by western blot in vitro and immunohistochemistry in vivo.
By analyzing the plasma circRNA microarrays in NKTCL, 6137 circRNAs were up-regulated and 6190 circRNAs were down-regulated. The relative expressions of circADARB1 were significantly higher in NKTCL patients. The knockdown of circADARB1 inhibited proliferation of NKTCL cells in vitro and in vivo. CircADARB1 could bind to miR-214-3p in the downstream and regulate the expression of p-Stat3. In nude mice tumor tissue, p-Stat3 was under-expressed in the circADARB1 knockdown group.
CircADARB1 was highly expressed in NKTCL plasma and circADARB1 was a potential biomarker to assist diagnosis and predict the response in NKTCL. CircADARB1 bound up to miR-214-3p and regulated p-Stat3.
自然杀伤/T细胞淋巴瘤（NKTCL）是一种罕见且侵袭性强的非霍奇金淋巴瘤亚型。环状RNA已显示出成为血浆生物标志物的巨大潜力。在本研究中，我们旨在确定环状RNA在NKTCL中的诊断、预后价值及生物学功能。
对NKTCL患者和健康供体的血浆进行环状RNA微阵列检测。通过qRT-PCR验证目标环状RNA的相对表达。我们进行了体外和体内功能实验。生物信息学预测目标环状RNA的靶标miRNA，并通过双荧光素酶报告基因检测法检测结合位点。通过蛋白质免疫印迹法在体外预测并检测下游靶蛋白，通过免疫组化法在体内进行检测。
通过分析NKTCL患者的血浆环状RNA微阵列，发现6137种环状RNA上调，6190种环状RNA下调。NKTCL患者中环状ADARB1的相对表达显著更高。敲低环状ADARB1可抑制NKTCL细胞在体外和体内的增殖。环状ADARB1可在下游与miR-214-3p结合并调节p-Stat3的表达。在裸鼠肿瘤组织中，环状ADARB1敲低组的p-Stat3表达下调。
环状ADARB1在NKTCL血浆中高表达，是辅助NKTCL诊断和预测反应的潜在生物标志物。环状ADARB1与miR-214-3p结合并调节p-Stat3。
