Musashi-1 regulates AKT-derived IL-6 autocrinal/paracrinal malignancy and chemoresistance in glioblastoma

Hsiao Yun Chen, Liang-ting Lin, Mong Lien Wang, Shu Hsien Lee, Ming Long Tsai, Chi Chang Tsai, Wei Hsiu Liu, Tzu Chien Chen, Yi Ping Yang, Yi Yen Lee, Yuh Lih Chang, Pin I. Huang, Yi Wei Chen, Wen Liang Lo, Shih Hwa Chiou, Ming Teh Chen

Research output: Journal article publicationJournal articleAcademic researchpeer-review

46 Citations (Scopus)


Glioblastoma multiform (GBM) is one of the most lethal human malignant brain tumors with high risks of recurrence and poor treatment outcomes. The RNA-binding protein Musashi-1 (MSI1) is a marker of neural stem/progenitor cells. Recent study showed that high expression level of MSI1 positively correlates with advanced grade of GBM, where MSI1 increases the growth of GBM. Herein, we explore the roles of MSI1 as well as the underlying mechanisms in the regulation of drug resistance and tumorigenesis of GBM cells. Our results demonstrated that overexpression of MSI1 effectively protected GBM cells from drug-induced apoptosis through down-regulating pro-apoptotic genes; whereas inhibition of AKT withdrew the MSI1-induced anti-apoptosis and cell survival. We further showed that MSI1 robustly promoted the secretion of the pro-inflammatory cytokine IL-6, which was governed by AKT activity. Autonomously, the secreted IL-6 enhanced AKT activity in an autocrine/paracrine manner, forming a positive feedback regulatory loop with the MSI1-AKT pathway. Our results conclusively demonstrated a novel drug resistance mechanism in GBM cells that MSI1 inhibits drug-induced apoptosis through AKT/IL6 regulatory circuit. MSI1 regulates both cellular signaling and tumor-microenvironmental cytokine secretion to create an intra- and intercellular niche for GBM to survive from chemo-drug attack.
Original languageEnglish
Pages (from-to)42485-42501
Number of pages17
Issue number27
Publication statusPublished - 5 Jul 2016
Externally publishedYes


  • apoptosis
  • chemoresistance
  • GBM
  • IL-6
  • Musashi-1

ASJC Scopus subject areas

  • Oncology


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