Zhi-Bin Liao1, Xiao-Long Tan1, Ke-Shuai Dong1, Hong-Wei Zhang1, Xiao-Ping Chen1, Liang Chu2, Bi-Xiang Zhang3. 1. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 2. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: liangchu@tjh.tjmu.edu.cn. 3. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: bixiangzhang@163.com.
Abstract
BACKGROUND: Increasing evidence indicates that aberrant micro (mi)RNA-448 expression plays a critical role in the progression of several human cancers. However, the function of miRNA-448 in hepatocellular carcinoma (HCC) has not been fully investigated. METHODS: miRNA-448 expression levels in HCC tissues, adjacent non-cancerous tissues (ANTs), and HCC cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR). HCC cells were treated with a miRNA-448 mimic or inhibitor, followed by cell viability measurements with the CCK-8 assay. Venn diagram analysis predicted, and dual luciferase reporter assays verified, the target gene of miRNA-448. Expression of the target gene was detected by qRT-PCR and immunohistochemistry. Growth of miRNA-448- or target gene-expressing HCC xenograft tumors in nude mice was measured. RESULTS: miRNA-448 was expressed at a lower level in HCC tissues than ANTs, and correlated with a larger tumor size, incomplete tumor encapsulation, and advanced Barcelona Clinic Liver Cancer stage. miRNA-448 inhibited HCC cell growth. The downstream target of miRNA-448 was BCL-2, which was highly expressed in HCC tissues and its mRNA level was negatively correlated with miRNA-448 expression. In vivo, BCL-2 attenuated the tumor inhibiting effect of miRNA-448. CONCLUSION: miRNA-448 functions as a tumor suppressor by targeting BCL-2 in HCC.
BACKGROUND: Increasing evidence indicates that aberrant micro (mi)RNA-448 expression plays a critical role in the progression of several humancancers. However, the function of miRNA-448 in hepatocellular carcinoma (HCC) has not been fully investigated. METHODS:miRNA-448 expression levels in HCC tissues, adjacent non-cancerous tissues (ANTs), and HCC cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR). HCC cells were treated with a miRNA-448 mimic or inhibitor, followed by cell viability measurements with the CCK-8 assay. Venn diagram analysis predicted, and dual luciferase reporter assays verified, the target gene of miRNA-448. Expression of the target gene was detected by qRT-PCR and immunohistochemistry. Growth of miRNA-448- or target gene-expressing HCC xenograft tumors in nude mice was measured. RESULTS:miRNA-448 was expressed at a lower level in HCC tissues than ANTs, and correlated with a larger tumor size, incomplete tumor encapsulation, and advanced Barcelona Clinic Liver Cancer stage. miRNA-448 inhibited HCC cell growth. The downstream target of miRNA-448 was BCL-2, which was highly expressed in HCC tissues and its mRNA level was negatively correlated with miRNA-448 expression. In vivo, BCL-2 attenuated the tumor inhibiting effect of miRNA-448. CONCLUSION:miRNA-448 functions as a tumor suppressor by targeting BCL-2 in HCC.