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.
Highlights
Laryngeal carcinoma (LCC) is one of the most common head and neck malignant tumors around the world
We found that the expression of microRNA-125a was decreased in laryngeal carcinoma tissues and Hep-2 laryngeal cancer stem cells (Hep-2-Cancer stem cells (CSCs))
We found the miR-125a level in Hep-2-CSCs was 80 percent below the Hep-2-non-CSCs (Figure 1C). These results demonstrated the decrease of miR-125a in laryngeal cancer stem cells
Summary
Laryngeal carcinoma (LCC) is one of the most common head and neck malignant tumors around the world. Surgery, chemotherapy and radiation therapy are still the main methods for the treatment of primary laryngeal carcinoma. For patients with advanced LCC, the chemotherapy is considered as the only strategies for the treatment of cancer [3, 4]. Cancer stem cells (CSCs) are a group of cells achieved the ability to self-renew. They are supposed to be responsible for tumor formation and development [6, 7]. Previous studies have demonstrated that CD133 positive cancer stem cells would be a new effective target to reduce the postoperative recurrence and weaken the chemoresistance [9,10,11]
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