Therapeutic Potential of miR-4711-5p in Pancreatic Cancer: Antitumor Activity and Mechanistic Insights

Background/Aim: Pancreatic cancer remains one of the most lethal malignancies, with limited therapeutic options and an extremely poor prognosis. MicroRNAs (miRNAs), which regulate gene expression at the post-transcriptional level, have emerged as promising candidates for next-generation cancer therapeutics. The purpose of this study is to clarify the feasibility of miR-4711 as a potential therapeutic option against pancreatic cancer. Materials and Methods: The effects of miR-4711-5p were examined in pancreatic cancer cell lines with respect to cell proliferation, apoptosis, cancer stemness, cell cycle progression, and invasive capacity. RNA sequencing and in silico analyses were performed to identify potential target genes of miR-4711-5p. For in vivo safety evaluation, miR-4711-5p was formulated with super carbonate apatite, a delivery vehicle that is already amenable to large-scale production, and administered to cynomolgus monkeys. A nucleic acid dose equivalent to 10 times the effective dose observed in prior mouse efficacy studies was used. General clinical conditions, body weight, food consumption, ophthalmologic findings, electrocardiography, blood pressure, hematological and biochemical parameters, and histopathological changes were systematically assessed. Results: miR-4711-5p significantly suppressed cancer stemness, cell proliferation, and invasion, while inducing apoptosis and delaying cell cycle progression in pancreatic cancer cells. RNA sequencing and bioinformatic analyses identified MET, CTSA, and ANO1 as potential target genes of miR-4711-5p. In the cynomolgus monkey study, administration of miR-4711-5p formulated with super carbonate apatite resulted in no apparent differences compared with the control group in body weight, clinical observations, laboratory parameters, or histopathological findings, indicating the absence of treatment-related adverse effects even at a supra-therapeutic dose. Conclusions: These findings demonstrate that miR-4711-5p exerts potent antitumor effects against pancreatic cancer cells while exhibiting a favorable safety profile in a non-human primate model. Collectively, this study provides strong preclinical evidence supporting miR-4711-5p as a novel and safe therapeutic strategy for pancreatic cancer and represents an important step toward clinical application.