Novel role of miR-29a in pancreatic cancer autophagy and its therapeutic potential

Jason J. Kwon, Jeffrey A. Willy, Kayla A. Quirin, Ronald Wek, Murray Korc, Xiao-Ming Yin, Janaiah Kota

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) is a highly lethal malignancy that responds poorly to current therapeutic modalities. In an effort to develop novel therapeutic strategies, we found downregulation of miR-29 in pancreatic cancer cells, and overexpression of miR-29a sensitized chemotherapeutic resistant pancreatic cancer cells to gemcitabine, reduced cancer cell viability, and increased cytotoxicity. Furthermore, miR-29a blocked autophagy flux, as evidenced by an accumulation of autophagosomes and autophagy markers, LC3B and p62, and a decrease in autophagosome-lysosome fusion. In addition, miR-29a decreased the expression of autophagy proteins, TFEB and ATG9A, which are critical for lysosomal function and autophagosome trafficking respectively. Knockdown of TFEB or ATG9A inhibited autophagy similar to miR-29a overexpression. Finally, miR-29a reduced cancer cell migration, invasion, and anchorage independent growth. Collectively, our findings indicate that miR-29a functions as a potent autophagy inhibitor, sensitizes cancer cells to gemcitabine, and decreases their invasive potential. Our data provides evidence for the use of miR-29a as a novel therapeutic agent to target PDAC.

Original languageEnglish (US)
Pages (from-to)71635-71650
Number of pages16
JournalOncotarget
Volume7
Issue number44
DOIs
StatePublished - 2016

Fingerprint

Autophagy
Pancreatic Neoplasms
gemcitabine
Neoplasms
Adenocarcinoma
Therapeutics
Lysosomes
Cell Movement
Cell Survival
Down-Regulation
Growth
Autophagosomes
Proteins

Keywords

  • Autophagy
  • Gemcitabine
  • Metastasis
  • miR-29
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Novel role of miR-29a in pancreatic cancer autophagy and its therapeutic potential. / Kwon, Jason J.; Willy, Jeffrey A.; Quirin, Kayla A.; Wek, Ronald; Korc, Murray; Yin, Xiao-Ming; Kota, Janaiah.

In: Oncotarget, Vol. 7, No. 44, 2016, p. 71635-71650.

Research output: Contribution to journalArticle

Kwon, Jason J. ; Willy, Jeffrey A. ; Quirin, Kayla A. ; Wek, Ronald ; Korc, Murray ; Yin, Xiao-Ming ; Kota, Janaiah. / Novel role of miR-29a in pancreatic cancer autophagy and its therapeutic potential. In: Oncotarget. 2016 ; Vol. 7, No. 44. pp. 71635-71650.
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