Fazlul H Sarkar
Wayne State University School of Medicine, USA
Posters & Accepted Abstracts: J Cancer Sci Ther
We have conducted a study where the expression analysis of miR-21/miR-221 in conditioned media (exosomes collected from the conditioned medium) derived from PSCs/CAF cells and PSCs/CAF cells were used for further mechanistic experiments where the miRNA was assessed by quantitative RT-PCR in addition to multiple molecular approaches. In the current presentation, I will discuss the results of our study where the expression analysis of miR-21/miR-221 showed upregulation in the exosomes. In addition, miR-21 expression in stellate cells derived from normal pancreas was substantially lower when compared to PSCs or CAF cells derived from tumors. COLO-357 PC cells cultured in the presence of conditioned media derived from PSC/CAF cells led to a significant increase in clonogenicity and pancreatosphere formation. Furthermore, inhibition of miR-21 with antisense oligonucleotide (ASO) transfection resulted in decreased migration/invasive capacity of PSCs. Similarly, the effect of ASO-miR-221 transfection in CAF cells reduced the expression of NF-kB and K-Ras (target of miR-221) along with inhibition of migration/invasion. Moreover, miRNA expression profiling of PSCs, MIAPaCa-2 and COLO-357 cells and further validation by real time PCR, showed several differentially expressed miRNAs among which four was significantly up-regulated. In summary, these results suggest a crosstalk between PSCs/CAF cells and PC cells mediated through exosomes, resulting in the up-regulation of miR-21/miR-221 expression which in part may confer aggressiveness to PC. From these results, I will conclude that targeting these miRNAs could be useful for developing precision medicine for the prevention of tumor progression and/or for the treatment of PC.
Email: fsarkar@med.wayne.edu
Cancer Science & Therapy received 3968 citations as per Google Scholar report
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