MicroRNAs regulate most protein-coding genes, including genes important in cancer and other diseases. In our study, we demonstrated that the expression of miR-142 could be significantly suppressed in pancreatic cancer specimens and cell lines, comparing to their adjacent tissues and normal pancreatic cells. Growth and invasion of PANC-1 and SW1990 cells were attenuated by overexpression of miR-142 in vitro. With the help of bioinformatics analysis, hypoxia-inducible factor 1 (HIF-1α) was identified to be a direct target of miR-142, and luciferase reporter experiment confirmed this discovery. Overexpression of miR-142 decreases protein expression of HIF-1α. In the hypoxic microenvironment, HIF-1α was up-regulated while miR-142 was down-regulated. The invaded cells significantly increased in the hypoxic microenvironment comparing to the normoxic microenvironment. The hypoxia treatment induced cells' proliferation and invasion could be inhibited by miR-142 overexpression or HIF-1α inhibition. Moreover, expression of epithelial-mesenchymal transition (EMT) markers, Vimentin, VEGF-C and E-cad, was altered under hypoxia condition and regulated by miR-142/ HIF-1α. Above all, these findings provided insights on the functional mechanism of miR-142, suggested that the miR-142/HIF-1α axis may interfere with the proliferative and invasive property of pancreatic cancer cells, and indicated that miR-142 could be a potential therapeutic target for pancreatic cancer.
- Received September 13, 2016.
- Accepted December 22, 2016.
- © 2017. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.