title: Lin28B promotes melanoma growth by mediating a microRNA regulatory circuit.
abstract: It has been increasingly recognized that microRNAs (miRNAs) are often dysregulated in various human malignancies and can function as oncogenes or tumor-suppressors. However, the potential roles of miRNAs and components of the miRNA biogenesis pathway remain poorly defined in melanoma. Here, we systematically profiled miRNA expression in human melanocytes and melanoma cells, and identified a prominent function of miR-125a-5p in suppressing melanoma growth. Mechanistically, we discovered that Lin28B, a well-characterized inhibitor of let-7 miRNA biogenesis, was a direct target of miR-125a-5p in melanoma. We showed that the Lin28B was aberrantly expressed in a large proportion of melanoma patients and was functionally required for melanoma progression. We further demonstrated the involvement of let-7-dependent mechanism downstream of Lin28B, resulting in the activation of transforming growth factor-β signaling cascade. Collectively, our data implicate Lin28B as a novel oncogene in melanomagenesis by mediating a miRNA regulatory circuit.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China and.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Shengzhe
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China, School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China zhuangguanglei@gmail.com gao.weiqiang@sjtu.edu.cn.
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China, zhuangguanglei@gmail.com.
authors.forename: Guanglei
authors.initials: G
authors.lastname: Zhuang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C516326:LIN28B protein, human; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; C487931:mirnlet7 microRNA, human