miR-138-5p suppresses autophagy in pancreatic cancer by targeting SIRT1

She Tian1, Xingjun Guo2, Chao Yu1

  • 1Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Oncotarget
|January 5, 2017
PubMed

Insights

MicroRNA miR-138-5p suppresses autophagy in pancreatic cancer by targeting SIRT1. This microRNA inhibits tumor growth in vivo, offering a potential therapeutic target for pancreatic cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Aberrant autophagy is implicated in pancreatic cancer, but the role of microRNAs is unclear.
  • Hypoxia, a common feature in solid tumors, is known to induce autophagy.
  • Investigating microRNA regulation of autophagy in pancreatic cancer under hypoxic conditions is crucial.

Purpose of the Study:

  • To identify microRNAs involved in hypoxia-induced autophagy in pancreatic cancer.
  • To elucidate the mechanism by which miR-138-5p regulates autophagy and tumor growth.
  • To explore the therapeutic potential of miR-138-5p in pancreatic cancer.

Main Methods:

  • Microarray analysis of microRNA expression in pancreatic cancer cells under normoxic and hypoxic conditions.
  • Overexpression of miR-138-5p and assessment of autophagy markers.
  • Western blot, immunofluorescence, and electron microscopy to analyze autophagic flux.
  • Target validation using luciferase reporter assays and knockdown experiments.
  • In vivo studies to evaluate the effect of miR-138-5p on tumor growth.

Main Results:

  • miR-138-5p was significantly downregulated in hypoxia-stimulated pancreatic cancer cells.
  • Overexpression of miR-138-5p inhibited autophagy and autophagic flux independently of canonical pathways.
  • miR-138-5p directly targeted SIRT1, reducing its levels and subsequently affecting the SIRT1/FoxO1/Rab7 axis.
  • miR-138-5p suppressed pancreatic cancer cell autophagy and tumor growth in vivo.

Conclusions:

  • miR-138-5p acts as a tumor suppressor by inhibiting autophagy in pancreatic cancer.
  • The mechanism involves the targeting of SIRT1, leading to the suppression of the SIRT1/FoxO1/Rab7 pathway.
  • miR-138-5p represents a potential therapeutic target for pancreatic cancer treatment by modulating autophagy.

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