Department of Gastroenterology, The Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, China.
Department of General Surgery, Nantong Tumor Hospital, Nantong, Jiangsu, China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):4120-4130. doi: 10.1080/21691401.2019.1671857.
Gastric cancer (GC) is a global leading source of cancer-associated deaths. Circular RNAs (circRNAs) are a new type of non-coding RNA and promising biomarkers for diagnosis of multiple diseases such as cancer. Circ-PRMT5 expression was validated in 90 GC patient tissues and 6 different GC cells by qRT-PCR. Sublocalization of circ-PRMT5 in GC cells was determined in isolated nuclear and cytoplasmic RNAs. CircInteractome and miRanda were used to predict binding sites between circ-PRMT5 with micRNAs, and micRNAs with target mRNA. The correlation between genes was determined by the Pearson correlation analysis. The molecular mechanism was demonstrated by RNA precipitation, point mutation, luciferase activity and rescue experiments. Circ-PRMT5 expression was significantly higher in GC than in adjacent normal tissues, and GC patients with circ-PRMT5 high expression had shorter survival times. Functionally, circ-PRMT5 silence inhibited GC cell growth and invasion. Mechanism analysis showed that circ-PRMT5 sponged miR-145/miR-1304 to upregulate MYC expression and GC development. Our findings demonstrated that circ-PRMT5 function as an oncogene in GC patients by targeting miR-145/miR-1304/MYC axis. High circ-PRMT5 expression may provide a poor prognostic indicator of survival in GC patients and targeting circ-PRMT5/miR-145/miR-1304/MYC axis may be a novel therapeutic strategy for GC.
胃癌（GC）是全球癌症相关死亡的主要原因。环状 RNA（circRNAs）是一种新型的非编码 RNA，是多种疾病（如癌症）诊断的有前途的生物标志物。通过 qRT-PCR 在 90 个 GC 患者组织和 6 种不同的 GC 细胞中验证了 circ-PRMT5 的表达。通过分离核和细胞质 RNA 确定了 circ-PRMT5 在 GC 细胞中的亚定位。CircInteractome 和 miRanda 用于预测 circ-PRMT5 与 micRNA 之间、micRNA 与靶 mRNA 之间的结合位点。通过 Pearson 相关分析确定基因之间的相关性。通过 RNA 沉淀、点突变、荧光素酶活性和挽救实验证明了分子机制。circ-PRMT5 在 GC 中的表达明显高于相邻正常组织，并且 circ-PRMT5 高表达的 GC 患者的生存时间更短。功能上，circ-PRMT5 沉默抑制 GC 细胞的生长和侵袭。机制分析表明，circ-PRMT5 通过海绵吸附 miR-145/miR-1304 来上调 MYC 表达并促进 GC 发展。我们的研究结果表明，circ-PRMT5 通过靶向 miR-145/miR-1304/MYC 轴在 GC 患者中发挥癌基因作用。高 circ-PRMT5 表达可能是 GC 患者生存预后不良的指标，靶向 circ-PRMT5/miR-145/miR-1304/MYC 轴可能是 GC 的一种新的治疗策略。
