miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells
Joint Authors
Cui, Xiaobin
Li, Yong
Gong, Ping
Hou, Ji-xue
Huang, Wei
Ma, Xiao-ping
Wang, Yu-li
Li, Jing
Li, Na
Source
Journal of Immunology Research
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-08-02
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Li, Yong& Gong, Ping& Hou, Ji-xue& Huang, Wei& Ma, Xiao-ping& Wang, Yu-li…[et al.]. 2018. miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells. Journal of Immunology Research،Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1192974
Modern Language Association (MLA)
Li, Yong…[et al.]. miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells. Journal of Immunology Research No. 2018 (2018), pp.1-13.
https://search.emarefa.net/detail/BIM-1192974
American Medical Association (AMA)
Li, Yong& Gong, Ping& Hou, Ji-xue& Huang, Wei& Ma, Xiao-ping& Wang, Yu-li…[et al.]. miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells. Journal of Immunology Research. 2018. Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1192974
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192974