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miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells
- Source :
- Journal of Immunology Research, Vol 2018 (2018)
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- Although aberrant expression of miR-34a, an essential tumor suppressor miRNA, has been frequently observed in colon cancer (CCa), whether miR-34a can regulate CCa progression by modulating other facets of this malignancy (such as multidrug resistance, MDR) remains unknown. Here, we report for the first time that miR-34a expression was significantly downregulated in clinical CCa samples from oxaliplatin-resistant patients and in experimentally established multidrug-resistant CCa cells. By using histoculture drug response assay, we further confirmed that clinical CCa samples with lower miR-34a expression appeared to be more resistant to chemotherapy. Functionally, ectopic expression of exogenous miR-34a resensitized multidrug-resistant HCT-8/OR cells to oxaliplatin treatment, whereas miR-34a inhibition augmented the oxaliplatin resistance in chemosensitive HCT-8 cells. Mechanistically, miR-34a positively regulated the mRNA stability of the ornithine decarboxylase antizyme 2 (OAZ2) by directly targeting its three prime untranslated region (3′UTR). Consequently, suppression of the expression of miR-34a/OAZ2 signaling by chemotherapeutic agents significantly enhanced the activation of MDR-associated ATP-binding cassette (ABC) transporters and antiapoptosis pathways, thus leading to MDR development in CCa cells. Collectively, our combined analysis reveals a critical role of miR-34a/OAZ2 cascade in conferring a proper cellular response to CCa chemotherapy.
- Subjects :
- Immunologic diseases. Allergy
RC581-607
Subjects
Details
- Language :
- English
- ISSN :
- 23148861 and 23147156
- Volume :
- 2018
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Immunology Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.972ded52db424d94ab077092a637bf2b
- Document Type :
- article
- Full Text :
- https://doi.org/10.1155/2018/7498514