MicroRNA‑23b‑3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF‑κB signaling pathways

Abstract

MicroRNA (miR)‑23b‑3p plays an important role in tumor growth, proliferation, invasion and migration in pancre‑ atic cancer (PC). However, the function and mechanistic role of miR‑23b‑3p in the development of PC remains largely unknown. In the present study, the miR‑23b‑3p levels in the serum of patients with PC were found to be elevated, and the phosphorylation levels of Janus kinase (JAK)2, PI3K, Akt and NF‑κВ were found to be upregulated. In addition, miR‑23b‑3p was induced in response to interleukin‑6 (IL‑6), which is known to be involved in the progression of PC. Overexpression of miR‑23b‑3p, on the other hand, activated the JAK/PI3K and Akt/NF‑κB signaling pathways in PC cells, as evidenced by miR‑23b‑3p‑induced upregulation of phosphorylated (p‑) JAK2, p‑PI3K, p‑Akt and p‑NF‑κВ, as well as the downregula‑ tion of PTEN; and these effects were found to be reversible by miR‑23b‑3p inhibition. Furthermore, miR‑23b‑3p was found to downregulate PTEN by directly targeting the 3'‑untrans‑ lated region of PTEN mRNA. Notably, in an in vivo xenograft mouse model, overexpression of miR‑23b‑3p accelerated PC cell‑derived tumor growth, activated the JAK/Akt/NF‑κВ signaling pathway and promoted liver metastasis. In contrast, knockdown of miR‑23b‑3p suppressed tumor growth and metastasis as well as JAK/Akt/NF‑κВ signaling activity. In vivo imaging of the mice further confirmed the metastasis promoting role of miR‑23b‑3p in PC. These results suggested that miR‑23b‑3p enhances PC cell tumorigenesis and metas‑ tasis, at least, partially via the JAK/PI3K and Akt/NF‑κB signaling pathways. Therefore, targeting miR‑23b‑3p or the JAK/PI3K and Akt/NF‑κB signalings may be potential thera‑ peutic strategy against PC.