Sa1343 – Rates of Pancreatic Neoplasia in a Surveillance Program of High-Risk Individuals

Introduction: Peri-ampullary carcinoma is one of the most prevalent pancreatic malignancies in the world.Due to the lack of effective therapies, ever-increasing resistance against drugs, new approaches to effective treatment are warranted.Various factors regulate the drug resistance in cancer cells and metabolism is known to play one of the important roles in carcinogenesis.It is also evident that the phenomenon of metabolic reprogramming promotes tumor progression.So this study was designed to check the role of miRNAs in metabolic reprogramming in peri-ampullary carcinoma.Methodology: Two miRNAs; miR-107 and miR-325 were selected on the basis of existing literature and their role in metabolic reprogramming in different cancers.The expression of these miRNAs and their target genes Pyruvate kinase M2 (PKM2), Lactate dehydrogenase (LDH) and Glutaminase (GLS1) were analyzed in 30 peri-ampullary carcinoma surgical tissue samples along with healthy controls by q-PCR.Also, the circulating levels of miR-107 and miR-326 were assessed by q-PCR in corresponding blood samples (of above tissues) and were compared with circulating levels in 35 healthy controls.miR-107 and miR-326 were transfected individually and in combination in a pancreatic cancer cell line (MiaPaCa) and its effect on cell proliferation and cell survival (by MTT assay) was monitored.Alteration in metabolic response was measured by glucose uptake, lactate production, and glutamine production assay.Results: Significantly decreased expression of miR-107 and miR326 was found in both tissue and blood samples from patients compared to healthy controls.Also, PKM2, LDH, and GLS1 were highly expressed in tumor tissues compared to adjacent normal tissue.In-vitro transfection of miR-107 and mir-326 and co-transfection of mir-107 and mir-326 significantly decreased the expression of metabolic genes (PKM2, LDH, and GLS1).Simultaneously, the glucose uptake, lactate production, and glutamate production significantly decreased in cells transfected with individual miR-107 and 326 and in co-transfection.The transfection results also demonstrated decreased cell proliferation and survival.Conclusion: Our results indicate the role of miR 107 and 326 as the tumor suppressor and miRNA in pancreatic cancer by enhancing the sensitivity of cell towards the treatment.Hence, mir-107 and 326 may prove to be a promising target designing a novel therapeutic approach for the treatment of pancreatic cancer.