Downregulation of Msi1 suppresses the growth of human colon cancer by targeting p21cip1.
Musashi1 (Msi1), a member of the RNA-binding protein (RBP) family, is highly expressed in neural progenitor or stem cells for the maintenance of stemness as well as in various cancers. Emerging studies have demonstrated that it regulates cell processes by translational activation or suppresses specifically bound mRNA. In the present study, we initially reported remarkably increased expression of Msi1 in colon cancer tissues compared with adjacent non-tumor tissues. Knockdown of Msi1 significantly suppressed the proliferation, colony formation, tumorsphere formation and the progression of implanted colon cancers, and induced cell cycle attest at G0/G1 phase, along with the upregulated expression of p21(cip1). Reporter assays using a chimeric mRNA that combined luciferase and the 3'-UTR of p21(cip1) revealed that Msi1 decreased the reporter activity through the specific motif. Thus, the current results suggested that downregulation of Msi1 could inhibit the growth of colon cancers and Msi1 may be a promising therapeutic target molecule for human colon cancers.
Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Chao
C
Gao
Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Chun
C
Han
Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Qiyao
Q
Yu
Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Yue
Y
Guan
Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Na
N
Li
Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Jingjing
J
Zhou
Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Yanming
Y
Tian
Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Yi
Y
Zhang
D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D050759:Cyclin-Dependent Kinase Inhibitor p21; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins