Musashi 2 contributes to the sternness and chemoresistance of liver cancer stern cells via LIN28A activation

被引：51

作者：

Fang, Tian ^{[1
]}

Lv, Hongwei ^{[1
]}

Wu, Fuquan ^{[1
]}

Wang, Changzheng ^{[1
]}

Li, Ting ^{[1
]}

Lv, Guishuai ^{[1
,2
]}

Tang, Liang ^{[1
,2
]}

Guo, Linna ^{[1
,2
]}

Tang, Shanhua ^{[1
,2
]}

Cao, Dan ^{[1
,2
]}

Wu, Mengchao ^{[1
,2
]}

Yang, Wen ^{[1
,2
]}

Wang, Hongyang ^{[1
,2
,3
]}

机构：

[1] Second Mil Med Univ, Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, Shanghai 200438, Peoples R China

[2] Natl Ctr Liver Canc Res, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst, Renji Hosp,Sch Med, Shanghai 200032, Peoples R China

来源：

CANCER LETTERS | 2017年 / 384卷

基金：

中国国家自然科学基金;

关键词：

Liver cancer; MSI2; LIN28A; Sternness; TUMOR-INITIATING CELLS; HEPATOCELLULAR-CARCINOMA CELLS; THERAPEUTIC TARGET; SELF-RENEWAL; EXPRESSION; TRANSFORMATION; INVASION; FATE;

D O I：

10.1016/j.canlet.2016.10.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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, over expression of MSI2 resulted in the upregulation of Lin28A. Sternness 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 sternness and chemoresistance of liver CSC5 via LIN28A-dependent manner in HCC. Our findings revealed that MSI2 and Lin28A might be used as potential therapeutic targets for eradicating liver CSC5. (C) 2016 Published by Elsevier Ireland Ltd.

引用

页码：50 / 59

页数：10

共 32 条

[1] Hyaluronan-CD44v3 Interaction with Oct4-Sox2-Nanog Promotes miR-302 Expression Leading to Self-renewal, Clonal Formation, and Cisplatin Resistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma [J].