miR-211 modulates gemcitabine activity through downregulation of ribonucleotide reductase and inhibits the invasive behavior of pancreatic cancer cells.

Abstract

Only a subset of radically-resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from gemcitabine-based chemotherapy, thus the identification of novel prognostic factors is essential. In a high-throughput, microRNA (miRNA) array, miR-211 emerged as the best discriminating miRNA, with high expression associated with long survival. Here, we further explored the biological role of miRNA-211 in gemcitabine activity in the human PDAC cells (SUIT-2) subclones SUIT2-007 and SUIT2-028. Our results showed that miR-211 was expressed differentially in PDAC cells characterized by differential metastatic capability. In particular, S2-028 with lower metastatic ability had a higher expression of miR-211, compared to the S2-007 with higher metastatic capacity. Enforced expression of miR-211 via pre-miR-211 significantly reduced cell migration and invasion (e.g., 40% reduction of invasion of SUIT2 cells, compared to control; p<.05). Moreover, we demonstrated that induction of the miR-211 expression in the cells increased the sensitivity to gemcitabine and reduced the expression of its target ribonucleotide reductase subunit 2 (RRM2). In conclusion, miR-211 functional analyses suggested the role of RRM2 as a target of miR-211 in the modulation of gemcitabine sensitivity. Moreover, inhibition of cell migration and invasion might explain the less aggressive behavior of pancreatic cancer cells with higher expression levels of miR-211.

• Authors: Mina Maftouh, Amir Avan, Niccola Funel, Adam E Frampton, Hamid Fiuji, Serena Pelliccioni, Leandro Castellano, Valentina Galla, Godefridus J Peters, Elisa Giovannetti
• Journal: Nucleosides, nucleotides & nucleic acids (Nucleosides Nucleotides Nucleic Acids) Vol. 33 Issue 4-6 Pg. 384-93 ( 2014) ISSN: 1532-2335 [Electronic] United States
• PMID: 24940696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• MIRN211 microRNA, human
• MicroRNAs
• Deoxycytidine
• ribonucleotide reductase M2
• Ribonucleoside Diphosphate Reductase
• Gemcitabine

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects, genetics)
• Deoxycytidine (analogs & derivatives, pharmacology)
• Down-Regulation (drug effects, genetics)
• Humans
• MicroRNAs (genetics)
• Neoplasm Invasiveness
• Pancreatic Neoplasms (pathology)
• Ribonucleoside Diphosphate Reductase (genetics)
• Gemcitabine