Background The purpose of the study was to explore the precise parts of circ_0066147 (circular RNA [circRNA] scm-like with four mbt domains 1, circSFMBT1) in pancreatic cancer (PC) progression. Methods Ribonuclease R assay was used to confirm the stability of circ_0066147. circ_0066147, miR-326 and E2F transcription factor 2 (E2F2) expression levels was detected by quantitative reverse-transcription polymerase chain reaction or Western blot. Cell proliferation, apoptosis, migration and invasion abilities were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H -tetrazolium bromide, flow cytometry, wound-healing and transwell assays, respectively. Targeted relationships among circ_0066147, miR-326 and E2F2 were verified by the dual-luciferase reporter or RNA pull-down assay. Results circ_0066147 expression was upregulated in PC tissues and cells. circ_0066147 knockdown inhibited PC cell proliferation, migration, invasion and enhanced apoptosis in vitro , as well as weakened tumor growth in vivo . Mechanistically, circ_0066147 directly targeted miR-326 and circ_0066147 modulated E2F2 expression by miR-326. miR-326 mediated the regulation of circ_0066147 in PC cell behaviors in vitro . Furthermore, E2F2 was a functional target of miR-326 in modulating PC cell behaviors in vitro . Conclusion circ_0066147 regulated PC malignant progression in part depending on the miR-326/E2F2 axis, illuminating circ_0066147 was a potential prognostic marker and therapeutic target for PC management.

中文翻译：

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环状RNA circ_0066147对胰腺癌进展的作用机制

背景技术本研究的目的是探讨胰腺癌（PC）进展中circ_0066147（环状RNA [circRNA] scm样，具有四个mbt域1，circSFMBT1）的精确部分。方法采用核糖核酸酶R法检测circ_0066147的稳定性。通过定量逆转录聚合酶链反应或Western印迹检测circ_0066147，miR-326和E2F转录因子2（E2F2）的表达水平。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基-2 H-溴化四唑来评估细胞增殖，凋亡，迁移和侵袭能力，流式细胞术，伤口愈合和transwell分析。circ_0066147，miR-326和E2F2之间的靶向关系已通过双荧光素酶报告基因或RNA下拉测定法进行了验证。结果circ_0066147在PC组织和细胞中表达上调。circ_0066147敲低在体外抑制PC细胞增殖，迁移，侵袭和增强细胞凋亡，以及在体内减弱肿瘤的生长。从机理上讲，circ_0066147直接靶向miR-326，而circ_0066147通过miR-326调节E2F2表达。miR-326介导circ_0066147在体外PC细胞行为中的调控。此外，E2F2是miR-326在体外调节PC细胞行为的功能靶标。结论circ_0066147调节PC恶性程度部分取决于miR-326 / E2F2轴，照亮circ_0066147是PC管理的潜在预后标志物和治疗靶标。以及削弱体内肿瘤的生长。从机理上讲，circ_0066147直接靶向miR-326，而circ_0066147通过miR-326调节E2F2表达。miR-326介导circ_0066147在体外PC细胞行为中的调控。此外，E2F2是miR-326在体外调节PC细胞行为的功能靶标。结论circ_0066147调节PC恶性程度部分取决于miR-326 / E2F2轴，照亮circ_0066147是PC管理的潜在预后标志物和治疗靶标。以及削弱体内肿瘤的生长。从机理上讲，circ_0066147直接靶向miR-326，而circ_0066147通过miR-326调节E2F2表达。miR-326介导circ_0066147在体外PC细胞行为中的调控。此外，E2F2是miR-326在体外调节PC细胞行为的功能靶标。结论circ_0066147调节PC恶性程度部分取决于miR-326 / E2F2轴，照亮circ_0066147是PC管理的潜在预后标志物和治疗靶标。