Yi Tang1, Jianrong Yang1, Yonggang Wang2, Zhenyong Tang1, Sulai Liu2, Yuntian Tang3. 1. Department of Hepatobiliary Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi, 530000, PR China. 2. Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, Changsha, Hunan, 410000, PR China. 3. Department of Hepatobiliary Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi, 530000, PR China. Electronic address: xhliu1973@163.com.
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.
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.