IL-6 Accelerates the Proliferation and Metastasis of Pancreatic Cancer Cells via the miR-455-5p/IGF-1R Axis

Abstract

Background: Pancreatic cancer (PaC) is a highly malignant gastrointestinal tumor with invasive and metastatic characteristics. Interleukin-6 (IL-6), a negative prognostic marker, contributes to PaC progression. However, the mechanism of IL-6 in PaC is not yet fully understood. Methods: miR-455-5p levels were first tested by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in PaC tissues or cells. Subsequently, PaC cell-related functions were identified through CCK-8, Transwell, and Western blotting. Changes in miR-455-5p and IGF-1R expression were confirmed using RT-qPCR and Western blotting. miR-455-5p methylation was assessed by bisulfite sequencing PCR. Results: The authors discovered that miR-455-5p was expressed at low levels in PaC tissues and cells, and miR-455-5p expression was observably reduced by IL-6 in PaC cells. In addition, IL-6 dramatically induces miR-455-5p methylation in PaC cells. Functionally, the data revealed that IL-6 could facilitate the malignant properties of PaC cells, including proliferation, epithelial–mesenchymal transition, and metastasis. The authors found that miR-455-5p could suppress the progression of PaC cells by downregulating IGF-1R in PaC cells. Mechanistically, IL-6 downregulated miR-455-5p and upregulated IGF-1R, and miR-455-5p reduced IGF-1R expression through targeted binding. Conclusions: The authors demonstrated that the miR-455-5p/IGF-1R axis is necessary for the induction of IL-6 in PaC progression. Therefore, this study might provide a theoretical basis for the application of the IL-6/miR-455-5p/IGF-1R axis in the clinical therapy of PaC.