Recent research conducted at Baylor College of Medicine suggests that microRNA (also referred to as MiR-198) can possibly help in controlling and preventing the growth of pancreatic cancer cells. The results of this important discovery were published online in the Journal of Clinical Cancer Research.
The research results have helped to reveal a potential target for the management of cancer after primary modulation in a laboratory. Dr. Christian Marin-Muller, a former postdoctoral associate with the molecular surgeon research center in the Michael E. DeBakey Department of Surgery at BCM (who is also the first author of the study), suggested:
“In cancer, there are always different things that go wrong at different times. When one mechanism stops functioning properly, it affects other molecules. In the case of pancreatic cancer, a network of tumorigenic molecules is triggered when c expression is reduced.”
The research team revealed a tumor signature (via interacting network of factors) that determines the pancreatic cancer virulence and aggressive potential. MicroRNA (miR-198) is the interconnecting force that directly determines the functioning of tumorigenic network. Higher concentration of (miR-198) suggests a positive prognosis.
Pancreatic cancer has a very high mortality (with a 5-year survival rate of only 6%). In terms of incidence, it is the 9th most commonly occurring cancer in women and 10th most commonly occurring malignancy in men. According to estimates, the total number of cases of pancreatic cancer that will be diagnosed in 2013 are 45,220, with an overall projected mortality of 38,460.
BCM researcher Dr. Cathy Yao (who is also a professor of surgical research in the Michael E. DeBakey Department of Surgery) conducted research with her team in the past that showed that over-expression of mesothelin (also known as MSLN) can influence the metastasis, growth, and local invasion pancreatic cancer cells.
In the latest study, the research team analyzed the pancreatic tumor tissue from 37 patients and compared it to normal surrounding tissue. The study revealed that the two proteins (miR-198 and MSLN) are part of a complicated reciprocal regulatory loop. This also suggests that miR-198 is expressed by MSLN leading changes in the character of the molecules (suppression or over-expression) that is directly associated with aggressive potential of pancreatic tumor.
New treatment strategies
Dr.Yao, who is also the corresponding author of study, commented:
“Most of these factors that make up this network have not been revealed to be connected with pancreatic cancer before such as FSTL1, OCT-2, PBX-1, and VCP. We have dissected the mechanisms and found that they are all directly or indirectly modulated by the expression of miR-198.”
The research team observed that increased expression of miR-198 in mouse models is associated with the death of tumor cells (resulting in smaller tumor size and a lesser risk of cancer spreading), suggesting a promising pancreatic cancer treatment strategy.
The research team also suggested that, because the molecules discussed in the study are novel-based, higher level studies are recommended to better understand the molecular patho-physiology of pancreatic cancer cells. In addition, researchers still need to determine if multi-target oriented combination therapy can influence the efficacy of treatment. The research team also analyzed the factors regarding the effectiveness of miR-198 in the therapeutic management of other cancers.
Notable researchers who contributed in the study:
Investigators who significantly helped in the research from Baylor College of Medicine are; postdoctoral associate in surgical research, Dr. Dali Li; instructor of medicine – infections disease, Uddalak Bharadwaj; professor of surgical research, Dr. Changyi Johnny Chen; research coordinator department of surgery, Sally Hodges; professor of surgery, Dr. William Fisher; assistant professor of medicine in the NCI-desginated Dan L. Duncan Cancer Center, and Dr. Qianxing Mo. Dr. Min Li of the MD Anderson Cancer Center in Houston and China Medical University in Taiwan also contributed to the study.
Organizations such as the Cancer Prevention Research Institute of Texas, the National Institutes of Health Research Grants, and the Dan L. Duncan Cancer Center pilot grant funded the research.
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