Xue Minghui, Li Guangyan, Fang Xiangjie, Wang Lili, Jin Yuhong, Zhou Qinglan
1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinxiang Medical University, NO. 88 Jiankang Road, Weihui, 453100 Henan China.
2Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100 Henan China.
Cancer Cell Int. 2019 Feb 1;19:25. doi: 10.1186/s12935-019-0737-x. eCollection 2019.
Increasing studies indicated that circRNAs play critical roles in tumor progression. However, the roles and underlying mechanisms of circRNAs in gastric cancer (GC) remain largely unclear.
Microarray assay was used to screen the abnormally expressed circRNAs in GC. Cell viability assay, transwell assay and in vivo assay were performed to assess the effects of hsa_circ_0081143 on GC cells. Next, interaction between hsa_circ_0081143 and miR-646 was detected by luciferase reporter assay and RNA pull-down assay.
High throughput microarray assay showed that hsa_circ_0081143 was upregulated in GC tissues, which was further confirmed by qRT-PCR. Correlation analysis showed that high hsa_circ_0081143 expression was associated with the advanced TNM stage, lymphnode metastases, and poor overall survival of GC patients. Hsa_circ_0081143 inhibition decreased GC cells viability, invasion ability and induced the sensitivity of GC cells to cisplatin (DDP) in vitro. Mechanistically, we showed that hsa_circ_0081143 could act as an endogenous sponge by directly binding to miR-646 and downregulation of miR-646 efficiently reversed the inhibition of CDK6 induced by hsa_circ_008114 knockdown. Additionally, hsa_circ_0081143 silencing suppressed the tumorigenesis and remarkably enhance DDP inhibitory effects of GC cells in vivo.
Our study indicated a novel regulatory loop that hsa_circ_0081143/miR-646/CDK6 axis in GC progression. These data suggested that hsa_circ_0081143 might act as a potential novel therapeutic strategy for GC treatment.
越来越多的研究表明，环状RNA（circRNAs）在肿瘤进展中发挥关键作用。然而，circRNAs在胃癌（GC）中的作用及潜在机制仍不清楚。
采用微阵列分析筛选胃癌中异常表达的circRNAs。进行细胞活力分析、Transwell分析和体内分析，以评估hsa_circ_0081143对胃癌细胞的影响。接下来，通过荧光素酶报告基因分析和RNA下拉分析检测hsa_circ_0081143与miR-646之间的相互作用。
高通量微阵列分析显示，hsa_circ_0081143在胃癌组织中上调，qRT-PCR进一步证实了这一点。相关性分析表明，hsa_circ_0081143高表达与胃癌患者的TNM晚期、淋巴结转移及总体生存率低相关。抑制hsa_circ_0081143可降低胃癌细胞活力、侵袭能力，并诱导胃癌细胞在体外对顺铂（DDP）敏感。机制上，我们发现hsa_circ_0081143可作为内源性海绵，直接与miR-646结合，miR-646的下调有效逆转了hsa_circ_008114敲低诱导的CDK6抑制。此外，hsa_circ_0081143沉默抑制了体内肿瘤发生，并显著增强了DDP对胃癌细胞的抑制作用。
我们的研究表明了一种新的调控环，即hsa_circ_0081143/miR-646/CDK6轴在胃癌进展中的作用。这些数据表明，hsa_circ_0081143可能是一种潜在的新型胃癌治疗策略。
