MiR-19b-3p facilitates the proliferation and epithelial-mesenchymal transition, and inhibits the apoptosis of intrahepatic cholangiocarcinoma by suppressing coiled-coil domain containing 6

Abstract

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatocellular carcinoma, and microRNAs (miRNAs) play a vital role in its development. This study aimed to explore the molecular mechanism and clinical value of miR-19b-3p in ICC.

Methods: From March 2014 to October 2016, 94 pairs of specimens of ICC tissues and adjacent tissues were collected. Moreover, 5 ml of peripheral blood of 342 ICC patients who underwent ICC resection were collected before and one week after surgery. Luciferase activity assay was performed to confirm the regulation of miR-19b-3p on coiled-coil domain containing 6 (CCDC6). BALB/c nude mice were injected with CCLP-1 cells which were transfected with NC, miR-19b-3p mimic, miR-19b-3p inhibitor, pcDNA-CCDC6, si-CCDC6 or miR-19b-3p mimic + pcDNA-CCDC6.

Results: Results showed that miR-19b-3p levels were significantly higher in ICC tissues compared with adjacent tissues. Moreover, serum miR-19b-3p levels of ICC patients tended to decline after surgery, and were correlated with lymph node metastasis and histological grading of ICC. CCDC6, a new target gene of miR-19b-3p, was identified by four prediction databases. We confirmed that miR-19b-3p promoted cell proliferation and epithelial-mesenchymal transition (EMT), and inhibited apoptosis in ICC, while knockdown of CCDC6 reversed these effects. We also observed that miR-19b-3p/CCDC6 axis regulated the nuclear translocation of β-catenin. Furthermore, in vivo study also demonstrated that the miR-19b-3p/CCDC6 axis regulated EMT to promote ICC progression.

Conclusion: These results indicate that serum miR-19b-3p level is a crucial biomarker for ICC diagnosis and targeting miR-19b-3p-CCDC6 axis might be a promising strategy in ICC therapy.

Keywords: Coiled-coil domain containing 6; Epithelial-mesenchymal transition; Intrahepatic cholangiocarcinoma; microRNA.