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J u n e 1 1 - 1 3 , 2 0 1 8 | D u b l i n , I r e l a n d

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Page 39

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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.edu

BIOGRAPHY