Expression of Selected miRNAs in Normal and Cancer-Associated Fibroblasts and in BxPc3 and MIA PaCa-2 Cell Lines of Pancreatic Ductal Adenocarcinoma

Abstract

Therapy for pancreatic ductal adenocarcinoma remains challenging, and the chances of a complete cure are very limited. As in other types of cancer, the expression and role of miRNAs in controlling the biological properties of this type of tumor have been extensively studied. A better insight into miRNA biology seems critical to refining diagnostics and improving their therapeutic potential. In this study, we focused on the expression of miR-21, -96, -196a, -210, and -217 in normal fibroblasts, cancer-associated fibroblasts prepared from a ductal adenocarcinoma of the pancreas, and pancreatic carcinoma cell lines. We compared these data with miRNAs in homogenates of paraffin-embedded sections from normal pancreatic tissues. In cancer-associated fibroblasts and cancer cell lines, miRNAs differed significantly from the normal tissue. In detail, miR-21 and -210 were significantly upregulated, while miR-217 was downregulated. Similar transcription profiles were earlier reported in cancer-associated fibroblasts exposed to hypoxia. However, the cells in our study were cultured under normoxic conditions. We also noted a relation to IL-6 production. In conclusion, cultured cancer-associated fibroblasts and carcinoma cells reflect miR-21 and -210 expression similarly to the cancer tissue samples harvested from the patients.

Noncoding Ribonucleic Acids (RNAs) May Improve Response to Immunotherapy in Pancreatic Cancer

“…29 It has been observed that similar to PDAC tissue, cultured hypoxic CAFs exhibit an altered expression pattern of ncRNA. 30 Specifically, researchers found that hypoxic CAFs have increased expression of miR-21 and miR-210. 30 Previous studies illuminated that CAFs can overexpress specific ncRNAs, such as miR-92 and circEIF3K, which can finally upregulate immune checkpoint proteins, such as PD-L1, in cancer cells and enhance tumor immune evasion.…”

“…30 Specifically, researchers found that hypoxic CAFs have increased expression of miR-21 and miR-210. 30 Previous studies illuminated that CAFs can overexpress specific ncRNAs, such as miR-92 and circEIF3K, which can finally upregulate immune checkpoint proteins, such as PD-L1, in cancer cells and enhance tumor immune evasion. 31,32 Luciferase assay indicated that miR-92 can target and downregulate the expression of large tumor suppressor kinase 2 (LATS2), thereby attenuating the interaction between yes-associated protein 1 (YAP1) and LATS2 and weakening the inhibitory effect of LATS2 on YAP1-mediated expression of PD-L1.…”