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 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-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 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-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 metastasis, 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 therapeutic strategy against PC.

MicroRNA‑23b‑3p targets non‑SMC condensing I complex subunit G to promote proliferation and inhibit apoptosis of colorectal cancer cells via regulation of the PI3K/AKT signaling pathway

“…Consistent with the results of these aforementioned studies, the findings of the current study revealed that miR-23b-3p expression was downregulated in CRC tissues. However, other studies have reported that miR-23b-3p expression is upregulated in several types of malignant tumor, including renal ( 28 ), lung ( 29 ) and pancreatic cancer ( 30 , 31 ). The discrepancy in these results may be due to differences in both the tissue types and the disease in question.…”

MiR-23b-3p Targeting NCAPG Promotes Cell Proliferation and Anti-Apoptosis By Regulating PI3K/AKT Signaling Pathway in Colorectal Cancer

“…Consistent with these studies, we observed the down-regulation of miR-23b-3p in CRC tissues. However, some scholars have been reported that up-regulation of miR-23b-3p in several types of malignant tumors, including pancreatic cancer [39], renal cancer [40], lung cancer [41] and pancreatic cancer [42]. The discrepant results may be due to the different tissues or diseases.…”

A Substance P (SP)/Neurokinin-1 Receptor Axis Promotes Perineural Invasion of Pancreatic Cancer and Is Affected by lncRNA LOC389641

“…The Akt/NF- κ B-associated signaling pathways were promoted by mRNAs, microRNA (miRNAs), and lncRNAs in pancreatic cancers. Other studies showed that the Akt/NF- κ B signaling pathway was promoted by CCN1 [ 34 ] and miRNA-23b-3p [ 35 ] and involved in the tumorigenicity of pancreatic cancer. Our present study suggests that the NK-1R/Akt/NF- κ B signaling system affecting PNI might be a novel target for pancreatic cancer therapy.…”