PDF(Pubmed)
Abstract：
Circular RNAs (circRNAs) are a cohort of non-coding RNAs generated by back-splicing events. Accumulating evidence supports the crucial role of circRNAs in human tumorigenesis, metastasis, and chemoresistance. However, the role and mechanism of circRNA circ_0087502 in pancreatic cancer are yet unknown.
The expression and function of circ_0087502 in pancreatic cancer were investigated using qRT-PCR and cell experiments. The predicted binding between circ_0087502 and microRNA-1179 (miR-1179), and between miR-1179 and TGFBR2, were examined using reporter assays.
Pancreatic cancer tissues and cell lines were discovered to express circ_0087502 at higher levels. Patients with pancreatic cancer who express circ_0087502 at high levels have a worse prognosis. In addition, circ_0087502 knockdown reduced the proliferation, migration, and invasion of pancreatic cancer cells and made them more sensitive to gemcitabine treatment. We found that circ_0087502 worked as a sponge for miR-1179, allowing miR-1179 to bind to the critical oncogene TGFBR2 in its 3\'-untranslated region (3\'-UTR). Pancreatic cancer cells were highly resistant to gemcitabine and had increased proliferation, migration, and invasion when miR-1179 was inhibited or overexpressed.
These results confirm that circ_0087502 activates the miR-1179/TGFBR2 axis to promote gemcitabine resistance in pancreatic cancer. Thus, our data might lay the groundwork for developing novel therapeutic strategies targeting circ_0087502 in pancreatic cancer patients.
The expression and function of circ_0087502 in pancreatic cancer were investigated using qRT-PCR and cell experiments. The predicted binding between circ_0087502 and microRNA-1179 (miR-1179), and between miR-1179 and TGFBR2, were examined using reporter assays.
Pancreatic cancer tissues and cell lines were discovered to express circ_0087502 at higher levels. Patients with pancreatic cancer who express circ_0087502 at high levels have a worse prognosis. In addition, circ_0087502 knockdown reduced the proliferation, migration, and invasion of pancreatic cancer cells and made them more sensitive to gemcitabine treatment. We found that circ_0087502 worked as a sponge for miR-1179, allowing miR-1179 to bind to the critical oncogene TGFBR2 in its 3\'-untranslated region (3\'-UTR). Pancreatic cancer cells were highly resistant to gemcitabine and had increased proliferation, migration, and invasion when miR-1179 was inhibited or overexpressed.
These results confirm that circ_0087502 activates the miR-1179/TGFBR2 axis to promote gemcitabine resistance in pancreatic cancer. Thus, our data might lay the groundwork for developing novel therapeutic strategies targeting circ_0087502 in pancreatic cancer patients.
摘要：
■环状RNA(circRNAs)是由反向剪接事件产生的一组非编码RNA。越来越多的证据支持circRNAs在人类肿瘤发生中的关键作用，转移,和化学抗性。然而,circRNAcirc_0087502在胰腺癌中的作用和机制尚不清楚。
■使用qRT-PCR和细胞实验研究了circ_0087502在胰腺癌中的表达和功能。circ_0087502和microRNA-1179（miR-1179）之间的预测结合，在miR-1179和TGFBR2之间，使用报告子测定法进行检查。
■发现胰腺癌组织和细胞系以更高水平表达circ_0087502。高水平表达circ_0087502的胰腺癌患者预后较差。此外,circ_0087502敲低降低了增殖，迁移,和胰腺癌细胞的侵袭，使它们对吉西他滨治疗更敏感。我们发现circ_0087502作为miR-1179的海绵，允许miR-1179在其3'-非翻译区（3'-UTR）中与关键癌基因TGFBR2结合。胰腺癌细胞对吉西他滨有很高的耐药性，并且增殖增加，迁移,和侵袭时，miR-1179被抑制或过表达。
■这些结果证实，circ_0087502激活miR-1179/TGFBR2轴以促进胰腺癌中的吉西他滨耐药。因此，我们的数据可能为开发针对胰腺癌患者的circ_0087502的新型治疗策略奠定基础.
■使用qRT-PCR和细胞实验研究了circ_0087502在胰腺癌中的表达和功能。circ_0087502和microRNA-1179（miR-1179）之间的预测结合，在miR-1179和TGFBR2之间，使用报告子测定法进行检查。
■发现胰腺癌组织和细胞系以更高水平表达circ_0087502。高水平表达circ_0087502的胰腺癌患者预后较差。此外,circ_0087502敲低降低了增殖，迁移,和胰腺癌细胞的侵袭，使它们对吉西他滨治疗更敏感。我们发现circ_0087502作为miR-1179的海绵，允许miR-1179在其3'-非翻译区（3'-UTR）中与关键癌基因TGFBR2结合。胰腺癌细胞对吉西他滨有很高的耐药性，并且增殖增加，迁移,和侵袭时，miR-1179被抑制或过表达。
■这些结果证实，circ_0087502激活miR-1179/TGFBR2轴以促进胰腺癌中的吉西他滨耐药。因此，我们的数据可能为开发针对胰腺癌患者的circ_0087502的新型治疗策略奠定基础.
