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CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11
th
International Conference on
Journal of Medical Oncology and Therapeutics
|
Volume 3
Jingfang Ju et al., J Med Oncl Ther 2018, Volume 3
DEVELOPMENT OF NOVEL
miR-129 MIMIC WITH ENHANCED
THERAPEUTIC POTENTIAL TO
ELIMINATE RESISTANT COLON
CANCER STEM CELLS
Jingfang Ju, Andrew Felser, Ning Wu
and
Hua Liu
Stony Brook University, USA
T
reatment of advanced stage colorectal cancer remains a clinical
challenge associated with resistance to fluoropyrimidine based
chemotherapy. There is an urgent need to discover and develop new
strategies to enhance treatment efficacy in order to improve outcomes
for these patients. Non-coding microRNAs (miRNAs) have important
functions as oncogenes or tumor suppressor genes in the regulation of
cancer development and progression. Recently, miRNAs have emerged
as potential therapeutic options. We have identified miR-129 as tumor
suppressor miRNA and potential therapeutic candidate in colorectal
cancer. The expression of miR-129 expression is progressively lost in
colorectal cancer patients and is an important regulator of apoptosis
through the targeting of genes such as BCL-2. miR-129 was also found
to enhance 5-flurouracil (5-FU) cytotoxicity
in vitro
and
in vivo
. To further
developing miR-129 based novel therapeutics in colorectal cancer, we
have designed a modified version of miR-129 to enhance stability and
efficacy. The miR-129 mimic is significantly more potent in inhibiting
proliferation of a panel of colon cancer cell lines than the native miR-
129 precursor. The miR-129 mimic induces profound cell cycle arrest
at the G1/S checkpoint. We also demonstrated that the miR-129 mimic
retains its target specificity to BCL-2, TS and E2F3 as same as the native
miR-129 precursor. More importantly, the miR-129 mimic can eliminate
resistant colon cancer stem cells. The therapeutic potential of miR-
129 was demonstrated
in vivo
mouse colon tumor models as a potent
inhibitor of tumor growth and metastasis. As a result, miR-129 mimic has
a great potential to be further developed as a novel therapeutic drug for
treatment of advanced colorectal cancer.
Jingfang Ju is the Professor in the Department
of Pathology at Stony Brook Medicine/Stony
Brook University. He received his BS degree
from the Northeastern University and PhD in
molecular biology and biochemistry at the Uni-
versity of Southern California. He completed his
post-doctoral research fellowship at Yale Can-
cer Center, Yale University. Previously he has
served as the Senior Scientist and Team Leader
of high throughput genomics at a biopharma-
ceutical company, CuraGen Corporation in Con-
necticut.
jingfang.ju@stonybrookmedicine.eduBIOGRAPHY