Department of Gastroenterology, the Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.
Anticancer Drugs. 2021 Jan 1;32(1):22-33. doi: 10.1097/CAD.0000000000000992.
Colorectal cancer (CRC) is a frequently diagnosed cancer worldwide. Accumulating researches suggested that circular RNA 0007142 (circ_0007142) contributed to the progression and initiation of CRC. However, the molecular mechanism of circ_0007142 in CRC needs further research. Levels of circ_0007142, microRNA-455-5p (miR-455-5p), and serum- and glucocorticoid-induced protein kinase 1 (SGK1) were identified by quantitative real-time PCR. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide assay. Flow cytometry assay was used to detect cell apoptosis in SW480 and HCT116 cells. The relative proteins expression was detected by western blot. Cell migration and invasion were evaluated using transwell assay. Moreover, dual-luciferase reporter and RNA immunoprecipitation assays were conducted to determine the relationship between miR-455-5p and circ_0007142 or SGK1. Finally, xenograft tumor model was established to confirm the effect of circ_0007142 on CRC progression in vivo. Circ_0007142 and SGK1 levels were clearly increased, while miR-455-5p level was reduced in CRC tissues and cell lines. Circ_0007142 silencing promoted cell apoptosis and inhibited cell proliferation, migration and invasion, while these effects of circ_0007142 were partially abolished by miR-455-5p inhibitor in CRC cells. Circ_0007142 could sponge miR-455-5p to regulate SGK1 expression. Moreover, the effects of miR-455-5p on cell proliferation, apoptosis, migration and invasion could be partially reversed by SGK1 overexpression. Besides, circ_0007142 knockdown also suppressed the progression of CRC in vivo. Collectively, Circ_0007142/miR-455-5p/SGK1 axis regulated cell proliferation, apoptosis, migration and invasion of CRC cells, providing a probable therapy target for CRC.
结直肠癌（CRC）是一种在全球范围内经常被诊断出的癌症。越来越多的研究表明，环状 RNA 0007142（circ_0007142）有助于 CRC 的进展和发生。然而，circ_0007142 在 CRC 中的分子机制仍需要进一步研究。通过实时定量 PCR 鉴定 circ_0007142、微小 RNA-455-5p（miR-455-5p）和血清和糖皮质激素诱导的蛋白激酶 1（SGK1）的水平。通过 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基-2H-四唑-3-溴化物测定法测量细胞增殖。通过流式细胞术检测 SW480 和 HCT116 细胞中的细胞凋亡。通过 Western blot 检测相对蛋白表达。通过 Transwell 测定评估细胞迁移和侵袭。此外，进行双荧光素酶报告和 RNA 免疫沉淀测定以确定 miR-455-5p 与 circ_0007142 或 SGK1 之间的关系。最后，建立异种移植肿瘤模型以在体内证实 circ_0007142 对 CRC 进展的影响。在 CRC 组织和细胞系中，circ_0007142 和 SGK1 水平明显升高，而 miR-455-5p 水平降低。在 CRC 细胞中，circ_0007142 沉默促进细胞凋亡并抑制细胞增殖、迁移和侵袭，而 miR-455-5p 抑制剂部分消除了 circ_0007142 的这些作用。Circ_0007142 可以海绵 miR-455-5p 来调节 SGK1 表达。此外，SGK1 过表达部分逆转了 miR-455-5p 对细胞增殖、凋亡、迁移和侵袭的影响。此外，circ_0007142 敲低也抑制了体内 CRC 的进展。总之，Circ_0007142/miR-455-5p/SGK1 轴调节 CRC 细胞的增殖、凋亡、迁移和侵袭，为 CRC 提供了一个可能的治疗靶点。
