MicroRNA-520g confers drug resistance by regulating p21 expression in colorectal cancer

Yang Zhang, Liying Geng, Geoffrey A Talmon, Jing Wang

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Development of drug resistance is one of the major causes of colorectal cancer recurrence, yet mechanistic understanding and therapeutic options remain limited. Here, we show that expression of microRNA (miR)-520g is correlated with drug resistance of colon cancer cells. Ectopic expression of miR-520g conferred resistance to 5-fluorouracil (5-FU)- or oxaliplatin-induced apoptosis in vitro and reduced the effectiveness of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicated that miR-520g mediated drug resistance through down-regulation of p21 expression. Moreover, p53 suppressed miR-520g expression, and deletion of p53 up-regulated miR-520g expression. Inhibition of miR-520g in p53-/- cells increased their sensitivity to 5-FU treatment. Importantly, studies of patient samples indicated that expression of miR-520g correlated with chemoresistance in colorectal cancer. These findings indicate that the p53/miR-520g/p21 signaling axis plays an important role in the response of colorectal cancer to chemotherapy. A major implication of our studies is that inhibition of miR-520g or restoration of p21 expression may have considerable therapeutic potential to overcome drug resistance in colorectal cancer patients, especially in those with mutant p53.

Original languageEnglish (US)
Pages (from-to)6215-6225
Number of pages11
JournalJournal of Biological Chemistry
Volume290
Issue number10
DOIs
StatePublished - Mar 6 2015

Fingerprint

MicroRNAs
Drug Resistance
Colorectal Neoplasms
Pharmaceutical Preparations
Fluorouracil
oxaliplatin
Chemotherapy
Heterografts
Colonic Neoplasms
Restoration
Tumors
Therapeutics
Down-Regulation
Cells
Apoptosis
Recurrence
Drug Therapy
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

MicroRNA-520g confers drug resistance by regulating p21 expression in colorectal cancer. / Zhang, Yang; Geng, Liying; Talmon, Geoffrey A; Wang, Jing.

In: Journal of Biological Chemistry, Vol. 290, No. 10, 06.03.2015, p. 6215-6225.

Research output: Contribution to journalArticle

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