Related Experiment Video
Updated: Mar 9, 2026

Evaluating Autophagy Levels in Two Different Pancreatic Cell Models Using LC3 Immunofluorescence
Published on: April 28, 2023
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.
Abstract:
The role of microRNA in the aberrant autophagy that occurs in pancreatic cancer remains controversial. Because hypoxia is known to induce autophagy, we screened for differentially expressed microRNAs using a miRNA microarray with pancreatic cancer cells cultured under normoxic and hypoxic conditions. We found that miR-138-5p was among the most downregulated miRNA in hypoxia-stimulated cells, and that overexpression of miR-138-5p substantially reduced expression of autophagy markers. In addition, western blot and immunofluorescence analyses and electron microscopy revealed that miR-138-5p inhibited autophagy in pancreatic cancer cells and blocked serum starvation-induced autophagic flux independently of the typical autophagic signaling pathway. miR-138-5p had no effect on ATG3, ATG5, or ATG7, three primary autophagy-associated genes. Instead, miR-138-5p specifically targeted the SIRT1 3' untranslated region and suppressed autophagy by reducing the level of SIRT1, which acetylates FoxO1 and regulates autophagy via FoxO1/Rab7. SIRT1 or Rab7 knockdown blocked the SIRT1/FoxO1/Rab7 axis and suppressed autophagic inhibition by miR-138-5p. Finally, we found that miR-138-5p inhibited autophagy and tumor growth in vivo. These results indicate that miR-138-5p suppresses autophagy in pancreatic cancer by targeting SIRT1.
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.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway
Autophagy
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
MicroRNAs
MicroRNAs
Abnormal Proliferation

