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p85α is a microRNA target and affects chemosensitivity in pancreatic cancer

Paul A Toste1, Luyi Li1, Brian E Kadera1

  • 1Department of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.

The Journal of Surgical Research
|April 8, 2015
PubMed
Abstract

Insights

Increased phosphoinositide 3-kinase (PI3K) p85α expression enhances pancreatic cancer sensitivity to chemotherapy. MicroRNA-21 directly regulates p85α, influencing PI3K-AKT signaling and potentially improving patient survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) survival is correlated with phosphoinositide 3-kinase (PI3K) regulatory subunit p85α expression.
  • Understanding p85α's role in chemotherapy response and its regulation is crucial for PDAC treatment.

Purpose of the Study:

  • To investigate the impact of p85α expression on pancreatic cancer response to chemotherapy.
  • To elucidate the regulatory role of microRNA-21 (miR-21) in controlling p85α levels.

Main Methods:

  • Generated PDAC cells overexpressing p85α for gemcitabine sensitivity testing (MTT assay).
  • Utilized immunohistochemistry and in situ hybridization to analyze p85α and miR-21 expression in human PDAC tumors.
  • Performed Western blot and luciferase reporter assays to confirm miR-21's direct regulation of p85α and its effect on PI3K-AKT signaling.

Main Results:

  • Higher p85α expression significantly increased sensitivity to gemcitabine, correlating with reduced PI3K-AKT activation.
  • A significant inverse correlation was observed between miR-21 and p85α expression in human PDAC tumors.
  • In vitro, miR-21 overexpression decreased p85α levels and increased AKT phosphorylation, confirmed by luciferase assays.

Conclusions:

  • p85α expression is a key determinant of chemosensitivity in pancreatic ductal adenocarcinoma.
  • MicroRNA-21 directly regulates p85α, thereby influencing PI3K-AKT signaling pathways.
  • These findings offer insights into the mechanisms linking elevated p85α expression to improved PDAC patient survival.
Keywords:
ChemoresistancePIK3R1Pancreatic cancermiR-21p85α

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