MiR-1181 inhibits stem cell-like phenotypes and suppresses SOX2 and STAT3 in human pancreatic cancer

Cancer Lett. 2015 Jan 28;356(2 Pt B):962-70. doi: 10.1016/j.canlet.2014.11.007. Epub 2014 Nov 10.

Abstract

Recent studies have shown that cancer stem cells (CSCs) play an important role in the development of pancreatic cancer. Multiple oncogenes and signaling pathways have been confirmed to participate in the stemness maintenance and tumorigenicity of CSCs, including sex-determining region Y-box 2 (SOX2) and signal transduction and activation of transcription 3 (STAT3), which may provide novel therapeutic targets on pancreatic cancer. Here, we reported in pancreatic cancer tissues and cells that miR-1181 expression was markedly downregulated, and the low miR-1181 expression was associated with poorer overall survival and disease-free survival in pancreatic cancer patients. Furthermore, overexpression of miR-1181 inhibited, whereas downregulation of miR-1181 promoted, CSCs-like phenotypes in vitro and tumorigenicity in vivo in pancreatic cancer cells. Moreover, we demonstrated that miR-1181 directly suppressed SOX2 and STAT3 expression, resulting in downregulation of SOX2 and inhibition of the STAT3 pathway. Hence, our results suggest that miR-1181 plays a vital role in inhibiting the CSCs-like phenotypes in pancreatic cancer and might represent a potential target for anti-pancreatic cancer.

Keywords: Cancer stem cells; Pancreatic cancer; SOX2; STAT3; miR-1181.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Phenotype
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • SOXB1 Transcription Factors / antagonists & inhibitors
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • MicroRNAs
  • RNA, Messenger
  • RNA, Small Interfering
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • STAT3 Transcription Factor
  • STAT3 protein, human