Department of Oncology, Affiliated Hospital of Jining Medical University, No. 89 Guhuai Road, Jining, 272000, Shandong, China.
Department of Pathology, Jining No. 1, People's Hospital, No. 6 Jiankang Road, Jining, 272011, Shandong, China.
Dig Dis Sci. 2021 Jul;66(7):2261-2271. doi: 10.1007/s10620-020-06516-8. Epub 2020 Aug 1.
Gastric cancer (GC) is one of the most common digestive system diseases and yet lacks effective therapeutic regimen.
The aim of our present research was to probe the value of hsa_circ_0001017 in GC treatment.
qRT-PCR and Western blot were performed to detect gene and protein expressions, respectively. CCK-8 assay and clone formation assay were used to ensure the proliferation of GC cell lines. Transwell assay was performed to measure the migration and invasion of GC cell lines. The relationship between hsa_circ_0001017 and miR-197 and that between miR-197 and RHOB 3'-UTR were ensured using the luciferase reporter assay.
Decreased hsa_circ_0001017 was discovered in GC, and upregulation of hsa_circ_0001017 notably repressed proliferation, migration, and invasion of GC cell lines. We further certificated that hsa_circ_0001017 served as miR-197 sponge and suppressed the expression of miR-197. Moreover, hsa_circ_0001017 upregulation meaningfully accelerated RHOB expression in both gene and protein levels, and RHOB was a downstream target of miR-197. Overexpression of miR-197 could markedly restrain hsa_circ_0001017-induced RHOB increasing and stifle inhibition of hsa_circ_0001017 to the malignant phenotype of GC cell lines. Next, our results further confirmed that hsa_circ_0001017 increasing notably inhibited tumor growth, impeded miR-197 production, while it enhanced the expression of RHOB in vivo.
Our data demonstrated that upregulation of hsa_circ_0001017 could notably muffle the proliferation as well as the metastasis of GC cell lines and impede the formation of GC tumor via targeting to miR-197/RHOB signaling pathway. Our results evidenced that hsa_circ_0001017 may act as a rising biomarker for GC treatment.
胃癌（GC）是最常见的消化系统疾病之一，但缺乏有效的治疗方案。
本研究旨在探讨 hsa_circ_0001017 在 GC 治疗中的价值。
采用 qRT-PCR 和 Western blot 分别检测基因和蛋白表达。CCK-8 检测和克隆形成实验用于检测 GC 细胞系的增殖。Transwell 实验用于检测 GC 细胞系的迁移和侵袭。利用荧光素酶报告实验确定 hsa_circ_0001017 与 miR-197 之间以及 miR-197 与 RHOB 3'-UTR 之间的关系。
GC 中 hsa_circ_0001017 表达下调，hsa_circ_0001017 上调显著抑制 GC 细胞系的增殖、迁移和侵袭。我们进一步证实，hsa_circ_0001017 作为 miR-197 的海绵体，抑制 miR-197 的表达。此外，hsa_circ_0001017 上调在基因和蛋白水平上显著加速 RHOB 的表达，而 RHOB 是 miR-197 的下游靶标。miR-197 的过表达可显著抑制 hsa_circ_0001017 诱导的 RHOB 增加，并抑制 hsa_circ_0001017 对 GC 细胞系恶性表型的抑制作用。接下来，我们的结果进一步证实，hsa_circ_0001017 的上调显著抑制肿瘤生长，抑制 miR-197 的产生，同时增强体内 RHOB 的表达。
我们的数据表明，hsa_circ_0001017 的上调可显著抑制 GC 细胞系的增殖和转移，并通过靶向 miR-197/RHOB 信号通路抑制 GC 肿瘤的形成。我们的研究结果表明，hsa_circ_0001017 可能作为 GC 治疗的一个新的生物标志物。
