未经证实:环状RNA(circularRNAs,circRNAs)是内源性非编码RNAs,在许多生物过程中起着至关重要的作用,特别是在人类癌症中。最近的研究表明,circRNAs通过外泌体在肿瘤进展中发挥重要作用。然而,胃癌来源的外泌体的具体功能和circstau2在胃癌(GC)中的作用仍在很大程度上未知.
UNASSIGNED:通过circRNA微阵列分析和定量实时聚合酶链反应(qRT-PCR)鉴定了GC中差异表达的circRNAs。circstau2在GC中的作用通过circstau2敲低和过表达在体外和体内的功能测定得到证实。荧光原位杂交(FISH),免疫荧光,RNA免疫沉淀(RIP),双荧光素酶报告分析,采用qRT-PCR和Westernblot检测MBNL1、circSTAU2、miR-589和CAPZA1的表达及调控机制。此外,外泌体的作用通过透射电子显微镜和纳米视线粒子追踪分析得到证实.
未经授权:CircSTAU2,主要位于细胞质中,在GC中显著下调。CircSTAU2过表达抑制GC细胞增殖,在体外和体内的侵袭和迁移,而circSTAU2敲除具有相反的效果。CircSTAU2可以包裹在外泌体中并传递给受体细胞,并充当miR-589的海绵以减轻其对CAPZA1的抑制作用,从而抑制GC进展。此外,MBNL1充当circstau2的上游RNA结合蛋白,并显着影响circstau2的环化和表达。
未经ASSIGNED:外泌体传递的circstAU2可能作为一种肿瘤抑制因子,通过miR-589/CAPZA1轴抑制GC进展,这证明了GC的潜在治疗靶标。
UNASSIGNED: Circular RNAs (circRNAs) are endogenous noncoding RNAs that play vital roles in many biological processes, particularly in human cancer. Recent studies indicate that circRNAs play an important role in tumor progression through exosomes. However, the specific functions of gastric cancer-derived exosomes and the role of circSTAU2 in gastric cancer (GC) remain largely unknown.
UNASSIGNED: Differentially expressed circRNAs in GC were identified by circRNA microarrays analysis and quantitative real-time polymerase chain reaction (qRT-PCR). The role of circSTAU2 in GC was verified by circSTAU2 knockdown and overexpression with functional assays both in vitro and in vivo. Fluorescence in situ hybridization (FISH), immunofluorescence, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, qRT-PCR and Western blot were adopted to evaluate the expression and regulatory mechanism of MBNL1, circSTAU2, miR-589 and CAPZA1. Furthermore, the role of exosomes was demonstrated by transmission electron microscopy and nano-sight particle tracking analysis.
UNASSIGNED: CircSTAU2, mainly localized in the cytoplasm, was significantly downregulated in GC. CircSTAU2 overexpression inhibited GC cell proliferation, invasion and migration both in vitro and in vivo, while circSTAU2 knockdown had the inverse effect. CircSTAU2 could be wrapped in exosomes and delivered to recipient cells, and functioned as a sponge for miR-589 to relieve its inhibitory effect on CAPZA1, thus inhibiting GC progression. Furthermore, MBNL1 acted as the upstream RNA-binding protein of circSTAU2 and significantly influenced the circularization and expression of circSTAU2.
UNASSIGNED: Exosome-delivered circSTAU2 may act as a tumor suppressor that restrains GC progression via miR-589/CAPZA1 axis, which demonstrates a potential therapeutic target for GC.