Inhibition of HAX-1 by miR-125a reverses cisplatin resistance in laryngeal cancer stem cells.

Abstract

Chemoresistance is a major obstacle in chemotherapy of laryngeal carcinoma. Recently, studies indicate that cancer stem cells are responsible for chemotherapy failure. In addition, microRNAs play important roles in tumor initiation, development and multidrug resistance. In the present study, we found that the expression of microRNA-125a was decreased in laryngeal carcinoma tissues and Hep-2 laryngeal cancer stem cells (Hep-2-CSCs). MicroRNA-125a gain-of-function significantly increased the sensitivity of Hep-2-CSCs to cisplatin in vitro and in vivo. Combination with microRNA-125a mimics can decrease the half maximal inhibitory concentration of Hep-2-CSCs to cisplatin. Mechanically, we found that microRNA-125a reverses cisplatin resistance in Hep-2-CSCs by targeting Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1). Inhibition of HAX-1 by microRNA-125a significantly promotes the cisplatin-induced apoptosis in Hep-2-CSCs through mitochondrial pathway. In addition, multidrug resistance of Hep-2-CSCs to vincristine, etoposide and doxorubicin was greatly improved after the cells were transfected with microRNA-125a mimics. These dates strongly suggested the promotion of microRNA-125a/HAX-1 axis on chemotherapy of laryngeal carcinoma.

• Authors: Jiajia Liu, Qinglai Tang, Shisheng Li, Xinming Yang
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 52 Pg. 86446-86456 (Dec 27 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27880721 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antineoplastic Agents
• HAX1 protein, human
• MIRN125 microRNA, human
• MicroRNAs
• Cisplatin

Topics

• Adaptor Proteins, Signal Transducing (antagonists & inhibitors)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm
• Humans
• Laryngeal Neoplasms (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• MicroRNAs (physiology)
• Mitochondria (drug effects)
• Neoplastic Stem Cells (drug effects)