Colorectal cancer (CRC) has developed into the third leading cause of cancer-associated death worldwide. Studies have confirmed that circular RNAs (circRNAs) absorb microRNAs (miRNAs) to regulate the function of downstream genes. This study aimed to explore the underlying mechanism of circRNA 100146 in CRC. The expression of circRNA 100146, miRNA 149 (miR-149), and high mobility group AT-Hook 2 (HMGA2) was detected by quantitative real-time PCR (RT-qPCR). A series of biofunctional effects (cell viability, apoptosis, migration/invasion) were evaluated by the use of methyl thiazolyl tetrazolium (MTT), flow cytometry, and transwell assays. Protein levels were measured by Western blot assay. A xenograft model was established for in vivo experiments. The interactions among circRNA 100146, miR-149, and HMGA2 were evaluated by dual-luciferase reporter assay, RNA immunoprecipitation assays, or RNA pulldown assay. circRNA 100146 was upregulated in CRC tissues and cells. circRNA 100146 knockdown inhibited cell proliferation, promoted apoptosis, and suppressed migration and invasion in vitro and impeded tumor growth in vivo. Also, miR-149 was negatively regulated by circRNA 100146 and was targeted to HMGA2 and mediated its expression. Moreover, miR-149 interference abrogated the activities of silenced circRNA 100146 in proliferation, apoptosis, migration, and invasion. Furthermore, HMGA2 overexpression abated the effects described above caused by circRNA 100146 silencing, while the mutations on miR-149 binding sites in the 3′ untranslated region (3′-UTR) of HMGA2 led to its loss of this ability. circRNA 100146 knockdown repressed proliferation, enhanced apoptosis, and hindered migration and invasion in SW620 and SW480 cells through targeting the miR-149/HMGA2 axis.

中文翻译：

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环形RNA 100146通过MicroRNA 149 / HMGA2轴促进大肠癌进展

大肠癌（CRC）已发展成为全球范围内与癌症相关的死亡的第三大主要原因。研究证实，环状RNA（circRNA）吸收microRNA（miRNA）来调节下游基因的功能。这项研究旨在探讨circRNA 100146在CRC中的潜在机制。通过定量实时PCR（RT-qPCR）检测到circRNA 100146，miRNA 149（miR-149）和高迁移率组AT-Hook 2（HMGA2）的表达。通过使用甲基噻唑基四唑（MTT），流式细胞仪和transwell分析评估了一系列生物功能效应（细胞活力，凋亡，迁移/侵袭）。通过蛋白质印迹测定法测量蛋白质水平。建立了体内异种移植模型实验。circRNA 100146，miR-149和HMGA2之间的相互作用通过双萤光素酶报告基因测定，RNA免疫沉淀测定或RNA下拉测定进行评估。circRNA 100146在CRC组织和细胞中上调。circRNA 100146敲低抑制细胞增殖，促进细胞凋亡，并在体外抑制迁移和侵袭，并阻碍体内肿瘤的生长。同样，miR-149受circRNA 100146负调控，并靶向HMGA2，并介导其表达。此外，miR-149干扰消除了沉默的circRNA 100146在增殖，凋亡，迁移和侵袭中的活性。此外，HMGA2的过表达减轻了由circRNA 100146沉默引起的上述影响，而HMGA2的3'非翻译区（3'-UTR）中miR-149结合位点的突变导致其丧失这种能力。circRNA 100146敲低通过靶向miR-149 / HMGA2轴抑制SW620和SW480细胞中的增殖，增强凋亡并阻碍其迁移和侵袭。