Noncoding RNAs such as circular RNAs (circRNAs) are abundant in the human body and influence the occurrence and development of various diseases. However, the biological functions of circRNAs in colorectal cancer (CRC) are largely unknown. RT-qPCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circSPARC. Function-based experiments were performed using circSPARC knockdown and overexpression cell lines in vitro and in vivo, including CCK8, colony formation, transwell and metastasis models. Mechanistically, luciferase reporter assay, western blots, RNA immunoprecipitation (RIP), Chromatin isolation by RNA purification (ChIRP) and immunohistochemical stainings were performed. CircSPARC was upregulated in both the tissues and plasma of CRC patients. High expression of circSPARC was associated with advanced TNM stage, lymph node metastases, and poor survival. Silencing circSPARC inhibited CRC cell migration and proliferation in vitro and vivo. Mechanistically, circSPARC sponged miR-485-3p to upregulate JAK2 expression and ultimately contribute to the accumulation of phosphorylated (p)-STAT3. Besides, circSPARC recruited FUS, which facilitated the nuclear translocation of p-STAT3. These findings suggest that circSPARC might serve as a potential diagnostic and prognostic biomarker and a therapeutic target for CRC treatment by regulating JAK2/STAT3 pathway.

中文翻译：

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环状RNA circSPARC通过调节JAK/STAT通路增强结直肠癌的迁移和增殖

环状RNA（circRNA）等非编码RNA在人体中含量丰富，影响着各种疾病的发生和发展。然而，环状RNA在结直肠癌（CRC）中的生物学功能在很大程度上是未知的。RT-qPCR用于检测CRC细胞和组织中circRNA和mRNA的表达。荧光原位杂交 (FISH) 用于分析 circSPARC 的位置。在体外和体内使用 circSPARC 敲低和过表达细胞系进行基于功能的实验，包括 CCK8、集落形成、transwell 和转移模型。在机械上，进行了荧光素酶报告基因测定、蛋白质印迹、RNA 免疫沉淀 (RIP)、通过 RNA 纯化 (ChIRP) 分离染色质和免疫组织化学染色。CircSPARC 在 CRC 患者的组织和血浆中均上调。circSPARC 的高表达与晚期 TNM 分期、淋巴结转移和较差的生存率有关。沉默 circSPARC 在体外和体内抑制 CRC 细胞迁移和增殖。从机制上讲，circSPARC 吸收 miR-485-3p 以上调 JAK2 表达并最终促进磷酸化 (p)-STAT3 的积累。此外，circSPARC 招募了 FUS，这促进了 p-STAT3 的核转位。这些发现表明，circSPARC 可能通过调节 JAK2/STAT3 通路作为潜在的诊断和预后生物标志物和 CRC 治疗的治疗靶点。沉默 circSPARC 在体外和体内抑制 CRC 细胞迁移和增殖。从机制上讲，circSPARC 吸收 miR-485-3p 以上调 JAK2 表达并最终促进磷酸化 (p)-STAT3 的积累。此外，circSPARC 招募了 FUS，这促进了 p-STAT3 的核转位。这些发现表明，circSPARC 可能通过调节 JAK2/STAT3 通路作为潜在的诊断和预后生物标志物和 CRC 治疗的治疗靶点。沉默 circSPARC 在体外和体内抑制 CRC 细胞迁移和增殖。从机制上讲，circSPARC 吸收 miR-485-3p 以上调 JAK2 表达并最终促进磷酸化 (p)-STAT3 的积累。此外，circSPARC 招募了 FUS，这促进了 p-STAT3 的核转位。这些发现表明，circSPARC 可能通过调节 JAK2/STAT3 通路作为潜在的诊断和预后生物标志物和 CRC 治疗的治疗靶点。