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CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11th International Conference on
Journal of Medical Oncology and Therapeutics | Volume 3
Qi-En Wang et al., J Med Oncl Ther 2018, Volume 3
MAINTENANCE OF CANCER STEM
CELLS BY miRNA
Qi-En Wang, Amit Kumar Srivastava, Tiantian Cui, Chunhua
Han, Ananya Banerjee, Shuri Cai, Lu Liu, Zaibo Li, Xiaoli
Zhang, Selvendiran Karuppalya and Altaf A. Wanin
The Ohio State University Wexner Medical Center, USA
Cancer stem cells (CSCs) are considered to play a central role in
the cancer progression, metastasis and the development of drug
resistance. MicroRNAs (miRNAs) have important roles in regulating CSC
properties and are considered to be potential therapeutic targets. Diverse
aberrantly expressed miRNAs have been reported in ovarian cancer cells.
However, there have been few reports about miRNAs that were associated
with stemness and progression of ovarian cancer. In this study, miRNA
nano string profiling analysis was performed to screen crucial miRNAs
associated with characteristics and maintenance of CSCs in ovarian
cancer. We found that miR-328-3p was remarkably upregulated in ovarian
CSCs isolated from both ovarian cancer cell lines and primary ovarian
tumors compared to their corresponding bulk cancer cells. We further
demonstrated that enforced expression of miR-328-3p in ovarian cancer
cell lines expanded the population of ALDH+ cells, enhanced their sphere
formation ability, as well as increased their tumorigenicity. While inhibition
of miR-328-3p limited the ALDH+ cell population, reduced their sphere
formation capacity, and decreased their tumorigenicity. The orthotopic
ovarian xenograft assay also demonstrated that inhibition of miR-328-3p
impedes tumor growth and metastasis. The mechanistic investigation
revealed that repressed ERK1/2 phosphorylation in ovarian CSCs, mainly
due to reduced level of reactive oxygen species (ROS), contributes to
the enhanced expression of miR-328-3p, and the maintenance of CSCs.
Finally, we identified DDB2 as a direct target of miR-328-3p. Given our
previous finding that DDB2 is capable of limiting the CSC population
in ovarian cancers, we conclude that highly expressed miR-328-3p in
ovarian CSCs, probably due to repressed ERK1/2 activity, inhibits DDB2
expression, resulting in the expansion of these CSCs. Thus, targeting miR-
328 could be exploited to a novel strategy to eradicate CSCs in ovarian
cancer.
Qi-En Wang is an Associatet Professor in the
Department of Radiology and Comprehensive
Cancer Center at the Ohio State University.
Dr. Wang received his Bachelor Degree in Pre-
ventive Medicine in Shanxi Medical College in
1992, and obtained his PhD from Beijing Med-
ical University in 1997 in China. Then, Dr. Wang
worked as a Lecturer and Associate Professor
at Peking University Medical Center for 4 years.
During this time, his research was focused on
understanding how gene and environmental
exposure interact in carcinogenesis. In 2001,
He joined Dr. Altaf Wani’s laboratory at the Ohio
State University in the United States of America
to study the mechanism of DNA repair as a Re-
search Associate and Research Scientist. Since
2011, He has become a Tenure-track Assistant
Professor at the Ohio State University, and was
promoted to Associate Professor with Tenure in
2017.
BIOGRAPHY