Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1277 Jiefang Avenue, 430022, Wuhan, Hubei, China.
Department of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1277 Jiefang Avenue, 430022, Wuhan, Hubei, China.
Biochem Biophys Res Commun. 2022 Apr 16;600:101-108. doi: 10.1016/j.bbrc.2022.02.073. Epub 2022 Feb 20.
Cholangiocarcinoma (CCA) is the second most common liver malignancy with poor prognosis after hepatocellular carcinoma (HCC). Emerging evidences have proved that circular RNAs (circRNAs) are involved in the progression of multiple cancers, while their roles in tumorigenesis of CCA remains largely unclear. In the present study, we found circ_0000591 was upregulated in CCA cells and tissues. The highly expressed circ_0000591 could promote the proliferation, migration, invasion and carcinogenesis of CCA cells in vitro and in vivo. Functionally, circ_0000591 induced the proliferation, migration and invasion of CCA cells through sponging miR-326. Moreover, silencing of circ_0000591 attenuated LPS-induced anti-apoptosis of CCA cells through the TLR4/MyD88/IL6 pathway. In conclusion, this study revealed a novel regulatory mechanism that circ_0000591 contributed to the progression of CCA via miR-326/TLR4/MyD88/IL6 axis. These findings enhanced our knowledge of potential molecular mechanism involved in the malignant progression of CCA.
胆管癌(CCA)是继肝细胞癌(HCC)之后第二大常见的肝脏恶性肿瘤,预后不良。新出现的证据证明,环状 RNA(circRNAs)参与了多种癌症的进展,而它们在 CCA 肿瘤发生中的作用在很大程度上尚不清楚。在本研究中,我们发现 circ_0000591 在 CCA 细胞和组织中上调。高度表达的 circ_0000591 能够促进 CCA 细胞在体外和体内的增殖、迁移和侵袭以及致癌作用。功能上,circ_0000591 通过海绵吸附 miR-326 诱导 CCA 细胞的增殖、迁移和侵袭。此外,circ_0000591 的沉默通过 TLR4/MyD88/IL6 通路减弱了 CCA 细胞的 LPS 诱导的抗凋亡作用。总之,本研究揭示了一种新的调节机制,即 circ_0000591 通过 miR-326/TLR4/MyD88/IL6 轴促进 CCA 的进展。这些发现增强了我们对 CCA 恶性进展中涉及的潜在分子机制的认识。