Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma
The long-term survival rate of hepatocellular carcinoma (HCC) is poor. One of the reasons for the poor rate of survival is the high rate of recurrence caused by intrahepatic metastas is that adversely affects long-term outcome. Many studies have indicated that microRNAs play an important role in HCC...
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00973/full |
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| author | Xin-Yuan Lu Xin-Yuan Lu Xin-Yuan Lu Di Chen Xiao-Yuan Gu Jie Ding Ying-Jun Zhao Qian Zhao Qian Zhao Qian Zhao Ming Yao Zhiao Chen Xiang-Huo He Wen-Ming Cong Wen-Ming Cong Wen-Ming Cong |
| author_facet | Xin-Yuan Lu Xin-Yuan Lu Xin-Yuan Lu Di Chen Xiao-Yuan Gu Jie Ding Ying-Jun Zhao Qian Zhao Qian Zhao Qian Zhao Ming Yao Zhiao Chen Xiang-Huo He Wen-Ming Cong Wen-Ming Cong Wen-Ming Cong |
| author_sort | Xin-Yuan Lu |
| collection | DOAJ |
| description | The long-term survival rate of hepatocellular carcinoma (HCC) is poor. One of the reasons for the poor rate of survival is the high rate of recurrence caused by intrahepatic metastas is that adversely affects long-term outcome. Many studies have indicated that microRNAs play an important role in HCC, but there has been no research of clonal origins on recurrent HCC (RHCC) by analzing microRNAs. In the present study, we found that miR-483-5p was significantly upregulated in RHCC tissues of short-term recurrence (≤ 2 years) by miRNA microarray screening, and can significantly promote migration and invasion of HCC cells in vitro and increase intrahepatic metastasis in nude mice in vivo. Furthermore, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM), which significantly suppressed migration and invasion of HCC cells, was a direct target of miR-483-5p, and the re-introduction of ALCAM expression could antagonize the promoting effects of miR-483-5p on the capacity of HCC cells for migration and invasion. In addition, expression level of ALCAM was negatively correlated with microvascular invasion and tumor size recognized as prognostic factors. The cases which were negative for ALCAM expression had shorter time to recurrence than positive cases, and univariate and multivariate survival analyses showed that ALCAM was an independent risk factor of HCC recurrence. qRT-PCR and Western blotting showed that the expression of EMT related genes (MMP-2, MMP-9, E-caherin and vimentin) significantly changed as a result of interfering or overexpression of ALCAM, and ALCAM was significantly associated with EMT in HCC. These results suggest that the miR-483-5p/ALCAM axis is an important regulator in invasion and metastasis and biomarker for recurrence risk assessment of HCC. |
| first_indexed | 2024-12-23T11:57:34Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-23T11:57:34Z |
| publishDate | 2018-01-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-16043c66224649268c81ad5cd1a92c632022-12-21T17:48:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-01-01810.3389/fphar.2017.00973329957Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular CarcinomaXin-Yuan Lu0Xin-Yuan Lu1Xin-Yuan Lu2Di Chen3Xiao-Yuan Gu4Jie Ding5Ying-Jun Zhao6Qian Zhao7Qian Zhao8Qian Zhao9Ming Yao10Zhiao Chen11Xiang-Huo He12Wen-Ming Cong13Wen-Ming Cong14Wen-Ming Cong15Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, ChinaKey Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer of Ministry of Education, Second Military Medical University, Shanghai, ChinaShanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Shanghai, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Oncology, Shibei Hospital of Shanghai, Shanghai, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, ChinaKey Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer of Ministry of Education, Second Military Medical University, Shanghai, ChinaShanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Shanghai, ChinaState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, ChinaKey Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer of Ministry of Education, Second Military Medical University, Shanghai, ChinaShanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Shanghai, ChinaThe long-term survival rate of hepatocellular carcinoma (HCC) is poor. One of the reasons for the poor rate of survival is the high rate of recurrence caused by intrahepatic metastas is that adversely affects long-term outcome. Many studies have indicated that microRNAs play an important role in HCC, but there has been no research of clonal origins on recurrent HCC (RHCC) by analzing microRNAs. In the present study, we found that miR-483-5p was significantly upregulated in RHCC tissues of short-term recurrence (≤ 2 years) by miRNA microarray screening, and can significantly promote migration and invasion of HCC cells in vitro and increase intrahepatic metastasis in nude mice in vivo. Furthermore, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM), which significantly suppressed migration and invasion of HCC cells, was a direct target of miR-483-5p, and the re-introduction of ALCAM expression could antagonize the promoting effects of miR-483-5p on the capacity of HCC cells for migration and invasion. In addition, expression level of ALCAM was negatively correlated with microvascular invasion and tumor size recognized as prognostic factors. The cases which were negative for ALCAM expression had shorter time to recurrence than positive cases, and univariate and multivariate survival analyses showed that ALCAM was an independent risk factor of HCC recurrence. qRT-PCR and Western blotting showed that the expression of EMT related genes (MMP-2, MMP-9, E-caherin and vimentin) significantly changed as a result of interfering or overexpression of ALCAM, and ALCAM was significantly associated with EMT in HCC. These results suggest that the miR-483-5p/ALCAM axis is an important regulator in invasion and metastasis and biomarker for recurrence risk assessment of HCC.http://journal.frontiersin.org/article/10.3389/fphar.2017.00973/fullALCAMmiR-483-5phepatocellular carcinomaearly recurrenceinvasion and metastasisEMT |
| spellingShingle | Xin-Yuan Lu Xin-Yuan Lu Xin-Yuan Lu Di Chen Xiao-Yuan Gu Jie Ding Ying-Jun Zhao Qian Zhao Qian Zhao Qian Zhao Ming Yao Zhiao Chen Xiang-Huo He Wen-Ming Cong Wen-Ming Cong Wen-Ming Cong Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma Frontiers in Pharmacology ALCAM miR-483-5p hepatocellular carcinoma early recurrence invasion and metastasis EMT |
| title | Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma |
| title_full | Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma |
| title_fullStr | Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma |
| title_full_unstemmed | Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma |
| title_short | Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma |
| title_sort | predicting value of alcam as a target gene of microrna 483 5p in patients with early recurrence in hepatocellular carcinoma |
| topic | ALCAM miR-483-5p hepatocellular carcinoma early recurrence invasion and metastasis EMT |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00973/full |
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