title: Musashi 2 contributes to the stemness and chemoresistance of liver cancer stem cells via LIN28A activation.
abstract: Accumulating evidence suggests that cancer stem cells (CSCs), a small subset of cancer cells, are responsible for tumor initiation, progression, relapse and metastasis. Musashi 2 (MSI2), a RNA-binding protein, was proposed to be a potent oncogene playing key roles in myeloid leukemia and gastrointestinal malignancies. However, it remains elusive how MSI2 regulates stem cell features in HCC. Herein, we demonstrated that MSI2 was highly expressed in liver CSCs. Overexpression or knockdown of MSI2 altered CSC-related gene expression, self-renewal as well as resistance to chemotherapy in HCC cell lines. In mouse xenograft models, MSI2 could markedly enhance tumorigenicity. Mechanistically, overexpression of MSI2 resulted in the upregulation of Lin28A. Stemness and chemotherapeutic drug resistance induced by MSI2 overexpression were dramatically reduced by Lin28A knockdown. Moreover, MSI2 and LIN28A levels positively correlated with the clinical severity and prognosis in HCC patients. In conclusion, MSI2 might play a crucial role in sustaining stemness and chemoresistance of liver CSCs via LIN28A-dependent manner in HCC. Our findings revealed that MSI2 and Lin28A might be used as potential therapeutic targets for eradicating liver CSCs.
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China.
authors.forename: Tian
authors.initials: T
authors.lastname: Fang
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Lv
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China.
authors.forename: Fuquan
authors.initials: F
authors.lastname: Wu
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China; National Center for Liver Cancer Research, Shanghai, PR China.
authors.forename: Guishuai
authors.initials: G
authors.lastname: Lv
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China; National Center for Liver Cancer Research, Shanghai, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China; National Center for Liver Cancer Research, Shanghai, PR China.
authors.forename: Linna
authors.initials: L
authors.lastname: Guo
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China; National Center for Liver Cancer Research, Shanghai, PR China.
authors.forename: Shanhua
authors.initials: S
authors.lastname: Tang
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China; National Center for Liver Cancer Research, Shanghai, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Cao
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China; National Center for Liver Cancer Research, Shanghai, PR China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China; National Center for Liver Cancer Research, Shanghai, PR China. Electronic address: woodeasy66@hotmail.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Yang
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, PR China; National Center for Liver Cancer Research, Shanghai, PR China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, PR China. Electronic address: hywangk@vip.sina.com.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; C516326:LIN28B protein, human; C438151:MSI2 protein, human; D016601:RNA-Binding Proteins; C115011:oval cell marker OV-6
keywords: LIN28A; Liver cancer; MSI2; Stemness