miR-301a plays a pivotal role in hypoxia-induced gemcitabine resistance in pancreatic cancer.

Abstract

Hypoxia is a hallmark of pancreatic cancer (PC) and is associated with gemcitabine resistance. However, the mechanisms underlying hypoxia-induced gemcitabine resistance in PC remain greatly unknown. Our previous work showed that miR-301a, a hypoxia-sensitive miRNA, is involved in PC metastasis under hypoxia via regulation of its target gene P63. Here, we showed that miR-301a was upregulated in a NF-κB independent manner and promoted gemcitabine resistance under hypoxic conditions in vitro. In addition, TAp63, a member of the P63 family, reversed hypoxia-induced gemcitabine resistance by promoting degradation of HIF-1α. Furthermore, we proved that TAp63 was a functional downstream target of miR-301a and mediated the biological properties of miR-301a in PC. Taken together, these findings indicate that miR-301a exerts as a critical regulator involved in hypoxia-induced gemcitabine resistance in PC and may have potentials to be a therapeutic target for PC patients.

• Authors: Guangtao Luo, Xiang Xia, Xiaofeng Wang, Kundong Zhang, Jun Cao, Tao Jiang, Qian Zhao, Zhengjun Qiu
• Journal: Experimental cell research (Exp Cell Res) Vol. 369 Issue 1 Pg. 120-128 (08 01 2018) ISSN: 1090-2422 [Electronic] United States
• PMID: 29772221 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• MIRN301A microRNA, human
• MicroRNAs
• Deoxycytidine
• Gemcitabine

Topics

• Apoptosis (drug effects, genetics)
• Cell Proliferation (drug effects, genetics)
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Gene Expression Regulation, Neoplastic (drug effects)
• HEK293 Cells
• Humans
• MicroRNAs (physiology)
• Neoplasm Metastasis
• Pancreatic Neoplasms (drug therapy, genetics, pathology)
• Tumor Cells, Cultured
• Tumor Hypoxia (drug effects, genetics, physiology)
• Gemcitabine