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

MicroRNA (miR)-23b-3p plays an important role in tumor growth, proliferation, invasion and migration in pancreatic 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-[KAPPA]B were found to be upregulated. In addition, miR-23b-3p was induced in response to interleukin-6 (IU-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-[KAPPA]B signaling pathways in PC cells, as evidenced by miR-23b-3p-induced upregulation of phosphorylated (p-) JAK2, p-PI3K, p-Akt and p-NF-[KAPPA]B, as well as the downregulation 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'-untranslated 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-KB signaling pathway and promoted liver metastasis. In contrast, knockdown of miR-23b-3p suppressed tumor growth and metastasis as well as JAK/Akt/NF-[KAPPA]B 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 metastasis, at least, partially via the JAK/PI3K and Akt/NF-[KAPPA]B signaling pathways. Therefore, targeting miR-23b-3p or the JAK/PI3K and Akt/NF-[KAPPA]B signalings may be potential therapeutic strategy against PC. Key words: pancreatic cancer, metastasis, miR-23b-3p, PTEN, interleukin-6/Janus kinase/Akt/NF-[kappa]B