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

  • Authors:
    • Yunan Zhang
    • Dayang Chen
    • Guoqiang Zhang
    • Xiongbo Wu
    • Liangyun Zhou
    • Yexin Lin
    • Junli Ding
    • Fangmei An
    • Qiang Zhan

  • View Affiliations

  • Published online on: August 26, 2020     https://doi.org/10.3892/ol.2020.12021
  • Article Number: 160

  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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November-2020
Volume 20 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Zhang Y, Chen D, Zhang G, Wu X, Zhou L, Lin Y, Ding J, An F and Zhan Q: MicroRNA‑23b‑3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF‑κB signaling pathways. Oncol Lett 20: 160, 2020
APA
Zhang, Y., Chen, D., Zhang, G., Wu, X., Zhou, L., Lin, Y. ... Zhan, Q. (2020). MicroRNA‑23b‑3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF‑κB signaling pathways. Oncology Letters, 20, 160. https://doi.org/10.3892/ol.2020.12021
MLA
Zhang, Y., Chen, D., Zhang, G., Wu, X., Zhou, L., Lin, Y., Ding, J., An, F., Zhan, Q."MicroRNA‑23b‑3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF‑κB signaling pathways". Oncology Letters 20.5 (2020): 160.
Chicago
Zhang, Y., Chen, D., Zhang, G., Wu, X., Zhou, L., Lin, Y., Ding, J., An, F., Zhan, Q."MicroRNA‑23b‑3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF‑κB signaling pathways". Oncology Letters 20, no. 5 (2020): 160. https://doi.org/10.3892/ol.2020.12021