title: MicroRNA-105 suppresses cell proliferation and inhibits PI3K/AKT signaling in human hepatocellular carcinoma.
abstract: A growing amount of evidence supports that microRNA (miRNA) dysregulation is involved in cancer progression by directly downregulating multiple targets. Elucidating the underlying mechanism of miRNA in carcinogenesis may improve diagnostic and therapeutic strategies for malignancy. In the current study, we found that miR-105 expression was markedly downregulated in both hepatocellular carcinoma (HCC) cell lines and clinical HCC tissues, compared with normal human hepatocyte and adjacent non-cancerous tissues, respectively. Ectopic miR-105 expression suppressed, whereas inhibiting miR-105 promoted the proliferation and tumorigenicity of HCC cells both in vitro and in vivo. Furthermore, we demonstrated that miR-105 could deactivated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway by downregulating insulin receptor substrate-1, 3-phosphoinositide-dependent protein kinase-1 and AKT1 directly, resulting in increasing cyclin-dependent kinase inhibitors 1A and 1B (p21(Cip1) and p27(Kip1)) and decreasing cyclin D1 expression in HCC. Therefore, our results suggest that miR-105 functions as a potential tumor suppressor by inhibiting the PI3K/AKT signaling pathway and might represent a potential therapeutic target for HCC patients.
authors.affiliation: Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People's Republic of China, Department of Oncology and Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, People's Republic of China and Department of Hepatobiliary Surgery and Department of Clinical examination, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Shen
authors.affiliation: Department of Oncology and.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Rong
authors.affiliation: Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, People's Republic of China and.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery and.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People's Republic of China, Department of Oncology and Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, People's Republic of China and Department of Hepatobiliary Surgery and Department of Clinical examination, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, People's Republic of China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People's Republic of China, Department of Oncology and Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, People's Republic of China and Department of Hepatobiliary Surgery and Department of Clinical examination, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Clinical examination, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Clinical examination, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, People's Republic of China.
authors.forename: Tianxing
authors.initials: T
authors.lastname: Ji
authors.affiliation: Department of Clinical examination, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, People's Republic of China.
authors.forename: Sicong
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People's Republic of China, Department of Oncology and Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, People's Republic of China and Department of Hepatobiliary Surgery and Department of Clinical examination, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Clinical examination, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, People's Republic of China hongyun_jia@163.com.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Jia
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
chemical_list: C588223:MIRN105 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt