title: miR-203 enhances let-7 biogenesis by targeting LIN28B to suppress tumor growth in lung cancer.
abstract: Human cancers often exhibit increased microRNA (miRNA) biogenesis and global aberrant expression of miRNAs; thus, targeting the miRNA biogenesis pathway represents a novel strategy for cancer therapy. Here, we report that miR-203 enhances the biogenesis of tumor suppressor let-7 in lung cancer by directly targeting LIN28B. Specially, we found that the LIN28B protein levels were dramatically increased in lung cancer tissues, but its mRNA levels did not differ significantly, suggesting that a post-transcriptional mechanism is involved in LIN28B regulation. Interestingly, miR-203 overexpression was accompanied by massive upregulation of a group of miRNAs, especially let-7, and the let-7 expression level was concordant with the miR-203 expression in lung cancer tissues, implying its biological relevance. Furthermore, we showed that miR-203 played a critical role in inhibiting the proliferation and promoting the apoptosis of lung cancer cells by suppressing LIN28B and enhancing let-7 biogenesis. In summary, our results establish a novel mechanism by which miR-203, LIN28B and let-7 are tightly linked to form a regulatory network in lung cancer cells. The findings shed light on the role of a specific miRNA as a modulator of miRNA biogenesis and provide basis for developing new strategies for lung cancer therapy.
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 210000, China.|The Fourth Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210000, China.|Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.|State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu 210093, China.|Nanjing multi-center biobank, Nanjing, Jiangsu 210008, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu 210093, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, Jiangsu 210000, China.
authors.forename: Zhicong
authors.initials: Z
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu 210093, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu 210093, China.
authors.forename: Xiuting
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu 210093, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Fourth Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 210000, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D017124:Conserved Sequence; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D059372:Nucleotide Motifs; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C516326:LIN28B protein, human; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human