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Volume 3
August 5-6, 2019 | Singapore
CANCER RESEARCH AND PHARMACOLOGY
STRUCTURAL BIOCHEMISTRY, STEM CELLS AND MOLECULAR BIOLOGY
24
th
International Conference on
International Congress on
&
Cancer Research 2019 & Structural Biochemistry 2019
August 5-6, 2019
Journal of Cancer and Metastasis Research
Clin Psychol Cog Sci, Volume 3
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 Mississippi Medical Center, 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.
swtbeck@uic.edu