title: miRNA-148b suppresses hepatic cancer stem cell by targeting neuropilin-1.
abstract: The existence of cancer stem cells (CSCs) is considered as a direct reason for the failure of clinic treatment in hepatocellular carcinoma (HCC). Growing evidences have demonstrated that miRNAs play an important role in regulation of stem cell proliferation, differentiation and self-renewal and their aberrances cause the formation of CSCs and eventually result in carcinogenesis. We recently identified miRNA-148b as one of the miRNAs specifically down-regulated in side population (SP) cells of PLC/PRF/5 cell line. However, it remains elusive how miRNA-148b regulates CSC properties in HCC. In the present study, we observed that overexpression or knockdown of miR-148b through lentiviral transfection could affect the proportion of SP cells as well as CSC-related gene expression in HCC cell lines. In addition, miR-148b blocking could stimulate cell proliferation, enhance chemosensitivity, as well as increase cell metastasis and angiogenesis in vitro. More importantly, miR-148b could significantly suppress tumorigenicity in vivo. Further studies revealed that Neuropilin-1 (NRP1), a transmembrane co-receptor involved in tumour initiation, metastasis and angiogenesis, might be the direct target of miRNA-148b. Taking together, our findings define that miR-148b might play a critical role in maintenance of SP cells with CSC properties by targeting NRP1 in HCC. It is the potential to develop a new strategy specifically targeting hepatic CSCs (HCSCs) through restoration of miR-148b expression in future therapy.
authors.affiliation: Fujian Provincial Key Laboratory of Tumor Biotherapy, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou 350014, P.R. China liuqinyingbio@163.com zqh2858@foxmail.
authors.forename: Qinying
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Fujian Provincial Key Laboratory of Tumor Biotherapy, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou 350014, P.R. China.
authors.forename: Yangmei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Abdominal Surgery, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou 350014, P.R. China.
authors.forename: Shenghong
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Abdominal Tumor, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou 350014, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Institute of Biomedical and Pharmaceutical Technology, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Biomedical and Pharmaceutical Technology, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Fujian Provincial Key Laboratory of Tumor Biotherapy, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou 350014, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Fujian Provincial Key Laboratory of Tumor Biotherapy, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou 350014, P.R. China.
authors.forename: Mingang
authors.initials: M
authors.lastname: Ying
authors.affiliation: Fujian Provincial Key Laboratory of Tumor Biotherapy, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou 350014, P.R. China liuqinyingbio@163.com zqh2858@foxmail.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D039942:Neuropilin-1
keywords: Neuropilin-1; cancer stem cell; hepatocellular carcinoma; microRNA-148b; side population cell