Jin Duochen, Huang Keting, Peng Lei, Xu Ping, Dang Yini, Yang Jiajia, Chen Meihong, Zhu Xudong, Wei Shuchun, Yan Jin, Zhang Guoxin
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 of Guangzhou Road, Nanjing 210029, China.
First Clinical Medical College of Nanjing Medical University, Nanjing, China.
Mol Ther Nucleic Acids. 2021 Jun 1;26:360-373. doi: 10.1016/j.omtn.2021.05.021. eCollection 2021 Dec 3.
Circular (circ)RNAs are widely involved in gastric cancer (GC) pathogenesis, and coiled-coil domain containing 6 () is a fused partner of multiple oncogenes; however, the underlying mechanisms of how circRNAs regulate expression in the progression and prognosis of GC remain unclear. Here, we discovered the circRNA derived from the gene locus (circDNA2) through RNA sequencing. By performing quantitative real-time PCR and fluorescence hybridization (FISH) assays with a human tissue microarray, circDNA2 was found to be highly expressed in GC tissues and associated with lymphatic invasion of GC patients. Knockdown of circDNA2 expression suppressed the proliferation of GC cells by reducing expression. Mechanistically, circDNA2 acted as a microRNA (miR)-149-5p sponge, which was confirmed to target by RNA pulldown and dual-luciferase reporter assays and rescue experiments. Both low miR-149-5p expression and high expression were related to unfavorable prognosis in GC patients. Moreover, GC patients with low miR-149-5p expression had shorter overall survival and a higher risk of chemotherapy resistance than those with high miR-149-5p expression. In summary, circDNA2 contributes to the growth and lymphatic metastasis of GC by upregulating expression by sponging miR-149-5p. The circDNA2/miR-149-5p/ axis might be developed as a therapeutic target and prognostic indicator for GC.
环状(circ)RNA广泛参与胃癌(GC)的发病机制,含卷曲螺旋结构域6()是多种癌基因的融合伴侣;然而,circRNA如何在GC的进展和预后中调节表达的潜在机制仍不清楚。在这里,我们通过RNA测序发现了源自基因位点的circRNA(circDNA2)。通过对人组织芯片进行定量实时PCR和荧光原位杂交(FISH)分析,发现circDNA2在GC组织中高表达,并与GC患者的淋巴浸润相关。敲低circDNA2表达可通过降低表达来抑制GC细胞的增殖。机制上,circDNA2作为微小RNA(miR)-149-5p的海绵,通过RNA下拉、双荧光素酶报告基因分析和挽救实验证实其靶向。低miR-149-5p表达和高表达均与GC患者的不良预后相关。此外,与高miR-149-5p表达的GC患者相比,低miR-149-5p表达的GC患者总生存期更短,化疗耐药风险更高。总之,circDNA2通过海绵化miR-149-5p上调表达,促进GC的生长和淋巴转移。circDNA2/miR-149-5p/轴可能成为GC的治疗靶点和预后指标。