Yang Jinhui, Qi Fuming, Tan Bo, Dai Guangcheng, Chen Rongxin, Wan Wenjie, Cheng Bo, Xue Boxin
Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China; Urology and Andrology Department, Shengli Oilfield Central Hospital, Dongying, Shandong Province, China.
Urology and Andrology Department, Shengli Oilfield Central Hospital, Dongying, Shandong Province, China.
Pathol Res Pract. 2022 Jun;234:153914. doi: 10.1016/j.prp.2022.153914. Epub 2022 Apr 26.
An increasing body of evidence suggest that circRNAs modulate various gene expression at the posttranscriptional level, affecting the development of cancers. Previous study suggested that circSPECC1 acted as an oncogene in some tumors, promoting the growth and metastasis of cancer cells. However, the role of circSPECC1 in bladder cancer (Bca) remains unknown.
RT-qPCR assay was applied to detect the expresion level of circRNA, miRNA and mRNA in Bca tissues and cells. CCK-8, cell colony formation and wound-healing assay were peformed to detect the effect of circSPECC1 on cell proliferation and migration. Nuclear mass separation, dual-luciferase reporter and RNA pull-down assay were used to investigate the molecular mechanisms underlying circSPECC1.
In this study, we found that circSPECC1 was significantly up-regulated in Bca tissues and cell lines. Increased expression of circSPECC1 contribute to poor prognosis of Bca. Further tests showed that knockdown of circSPECC1 impaired the proliferation and migration of Bca cells. Mechanically, circSPECC1 sponged miR-136-5p to promote the mRNA and protein expression of GNAS. Besides, enforced expression of GNAS significantly reversed the proliferation and migration inhibition mediated by circSPECC1 suppression.
In general, our study suggested that circSPECC1 contributed to the growth and metastasis of Bca and it is possible to become an ideal non-invasive biomarker for diagnosis and effective therapeutic target for treatment.
越来越多的证据表明,环状RNA(circRNAs)在转录后水平调节多种基因表达,影响癌症的发展。先前的研究表明,circSPECC1在某些肿瘤中作为癌基因发挥作用,促进癌细胞的生长和转移。然而,circSPECC1在膀胱癌(Bca)中的作用仍不清楚。
应用RT-qPCR检测Bca组织和细胞中circRNA、miRNA和mRNA的表达水平。进行CCK-8、细胞集落形成和伤口愈合实验,以检测circSPECC1对细胞增殖和迁移的影响。采用核质分离、双荧光素酶报告基因和RNA下拉实验来研究circSPECC1的分子机制。
在本研究中,我们发现circSPECC1在Bca组织和细胞系中显著上调。circSPECC1表达增加导致Bca预后不良。进一步的实验表明,敲低circSPECC1会损害Bca细胞的增殖和迁移。机制上,circSPECC1通过海绵吸附miR-136-5p来促进GNAS的mRNA和蛋白表达。此外,强制表达GNAS显著逆转了circSPECC1抑制介导的增殖和迁移抑制。
总的来说,我们的研究表明circSPECC1促进了Bca的生长和转移,它有可能成为诊断的理想非侵入性生物标志物和治疗的有效治疗靶点。