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Volume 2
Journal of Molecular Cancer
Cancer & Primary Healthcare 2019
May 20-21, 2019
Cancer Research & Oncology
Primary Healthcare and Medicare Summit
May 20-21, 2019 | Rome, Italy
25
th
Global Meet on
World Congress on
&
Transient resistance to DNA damaging agents is associated with expression of
microRNAs-135b and -196b in human leukemia cell lines
William T. Beck
University of Illinois at Chicago, USA
T
he acquisition of resistance to anticancer drugs is widely viewed as a key obstacle to successful cancer
therapy. However, detailed knowledge of the initial molecular events in the response of cancer cells to
these chemotherapeutic and stress responses, and how these lead to the development of chemoresistance,
remains incompletely understood. Using microRNA array and washout and rechallenge experiments, we
found that short term treatment of leukemia cells with etoposide led a few days later to transient resistance
that was associated with a corresponding transient increase in expression of ABCB1 mRNA, as well as miR-
135b and miR-196b. This phenomenon was associated with short-term exposure to genotoxic agents, such
as etoposide, topotecan, doxorubicin and ionizing radiation, but not agents that do not directly damage
DNA. Further, this appeared to be histiotype-specific, and was seen in leukemic cells, but not in cell lines
derived from solid tumors. Treatment of leukemic cells with either 5-aza-deoxycytidine or tricostatin A
produced similar increased expression of ABCB1, miR- 135b, and miR-196b, suggesting a role for epigenetic
regulation of this phenomenon. Bioinformatics analyses revealed that CACNA1E, ARHGEF2, PTK2,
SIAH1, ARHGAP6, and NME4 may be involved in the initial events in the development of drug resistance
following the upregulation of ABCB1, miR-135b and miR-196b. In summary, we report herein that short-
term exposure of cells to DNA damaging agents leads to transient drug resistance, which is associated with
elevations in ABCB1, miR-135b and miR-196b, and suggests novel components that may be involved in the
development of anticancer drug resistance.
wtbeck@uic.eduJ Mol Cancer, Volume 2