It has been found that the circular RNA (circRNA) CDR1as is upregulated in cholangiocarcinoma (CCA) tissues. In this study, we tried to explore the roles of CDR1as in CCA. CDR1as was overexpressed or knocked down in human CCA cells to assess the effects of CDR1as on cell behaviors and tumor xenograft growth. In vitro, the CDR1as level was significantly increased in CCA cell lines. The results showed that CDR1as promoted the cell proliferation, migration, invasion, and activation of the AKT3/mTOR pathway in CCA cells. Moreover, miR-641, a predicted target microRNA (miRNA) of CDR1as, could partially reverse the effects of CDR1as on cell behaviors in CCA cells. Furthermore, CDR1as improved tumor xenograft growth, and it could be attenuated by miR-641 in vivo Additionally, CDR1as expression was inversely correlated with miR-641 in CCA cells, and miR-641 could directly bind with CDR1as and its target genes, the AKT3 and mTOR genes. Mechanistically, CDR1as could bind with miR-641 and accelerate miR-641 degradation, which possibly leads to the upregulation of the relative mRNA levels of AKT3 and mTOR in RBE cells. In conclusion, our findings indicated that CDR1as might exert oncogenic properties, at least partially, by regulating miR-641 in CCA. CDR1as and miR-641 could be considered therapeutic targets for CCA.

中文翻译：

---

环状RNA CDR1as部分通过调节MicroRNA 641在胆管癌中具有致癌性。

已经发现，在胆管癌（CCA）组织中环状RNA（circRNA）CDR1as被上调。在这项研究中，我们试图探索CDR1as在CCA中的作用。CDR1as在人CCA细胞中过度表达或被敲低，以评估CDR1as对细胞行为和肿瘤异种移植物生长的影响。在体外，CCA细胞系中的CDR1as水平显着增加。结果表明，CDR1as促进了CCA细胞中AKT3 / mTOR途径的细胞增殖，迁移，侵袭和激活。此外，miR-641是CDR1as的预期靶微RNA（miRNA），可以部分逆转CDR1as对CCA细胞中细胞行为的影响。此外，CDR1as可以改善肿瘤异种移植物的生长，并且可以在体内被miR-641减弱。此外，CDR1as的表达与CCA细胞中miR-641呈负相关，miR-641可以直接与CDR1as及其靶基因AKT3和mTOR基因结合。从机制上讲，CDR1as可以与miR-641结合并加速miR-641降解，这可能导致RBE细胞中AKT3和mTOR的相对mRNA水平上调。总之，我们的发现表明，CDR1as可能通过调节CCA中的miR-641至少部分发挥致癌作用。CDR1as和miR-641可以视为CCA的治疗靶标。通过调节CCA中的miR-641。CDR1as和miR-641可以视为CCA的治疗靶标。通过调节CCA中的miR-641。CDR1as和miR-641可以视为CCA的治疗靶标。