Lipid Metabolism in Pancreatic Ductal Adenocarcinoma
Introduction. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant neoplasms1,3,4. When diagnosed, most patients are found to be in the advanced stages of PDAC3. Clinical symptoms for PDAC are non-specific such as nausea, weight loss, fatigue, and abdominal pain3. Additionally, PDAC has a 90% mortality rate at 5 years and a survival rate less than 7%2,3. Most treatments involve chemotherapy with surgery as the last resort and even then, only 10% of patients qualify for surgery3. Studies have suggested that lipid metabolism, via the enzyme fatty acid synthase, plays a crucial role in maintaining malignancy in PDAC cells4. Additionally, it as been shown that expression of miR-195 in inversely correlated with fatty acid synthase. Although not much is well known about micro-RNAs, it turns out that miR-195 plays an important role in the inhibition of fatty acid synthase expression and thus inhibit the proliferation and metastases of PDAC cells4. Methods. Cell cultures consisting of human PDAC cell lines and normal pancreatic ductal epithelial cells were obtained. RTq-PCR was performed to quantify mRNA and micro RNA. Remaining cells were also transfected with miR-195 mimickers, inhibitors and negative controls. Cells were then allowed to grow for 48 hours. Finally, protein extraction was performed and quantified via western blot analysis. Results. Within the cancer cell cultures, it was found via RT-qPCR, that miR-195 was significantly decreased when compared to normal pancreatic tissue4. By using miR-195 mimickers it was possible to restore the miR-195 expression and thus study its effects on pancreatic cancer cells. It was found that overexpression of miR-195 significantly reduced cell proliferation and induced cell cycle arrest in the G0/ G1 phase of the cell cycle4. Additionally, overexpression of miR-195 resulted in repression of cell invasion of pancreatic cancer cells. With regards to fatty acid synthase, via western blot analysis, both protein and mRNA levels of fatty acid synthase were suppressed by miR-195 overexpression4. Conclusion. Altering a cell’s metabolism is a hallmark of various cancers2,5. In the example of PDAC, it has been shown that fatty acid synthase plays an important role in synthesizing lipids required for cell proliferation. With the recent finding of mir-195 and with its ability to reduce expression of fatty acid synthase, reduce cell proliferation, and induce cell cycle arrest, it opens various doors to possible treatments for PDAC.
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