MicroRNA­19b inhibitors can attenuate the STAT3 signaling pathway in NPC C666­1 cells.

MicroRNA (miR)-19b is expressed in various types of tumors and may serve as a potential therapeutic target. The miR­17­92 cluster is upregulated in nasopharyngeal carcinoma (NPC) tissues and cells. miR­19b is a member of the miR­17­92 cluster; however, its expression and function in NPC are largely unknown. The present study aimed to investigate the expression and function of miR­19b in NPC cells. The miRCURY LNATM miRNA Inhibitor (miR­19b inhibitor and negative control) were transfected into C666­1 cells. The proliferation, apoptosis and migration of the cells were subsequently detected by the Cell Counting Kit­8 assay, flow cytometry and Transwell assay, respectively. Additionally, the expression of STAT3 signaling pathway­associated proteins [STAT3, pSTAT3 and suppressor of cytokine signaling 1 (SOCS1)] and the transcriptional targets of pSTAT3 [Bcl­2, myeloid leukemia protein 1 (Mcl­1) and cyclin D1] were detected by western blotting. The miR­19b inhibitor inhibited proliferation and migration and induced apoptosis of C666­1 cells. Furthermore, the miR­19b inhibitor upregulated the expression of SOCS1, a predicted target gene of miR­19b, and decreased the phosphorylation of STAT3 at Tyr705 and Ser727. These data indicated that upregulation of SOCS1, an endogenous inhibitor of STAT3 phosphorylation, attenuated the STAT3 signaling pathway in C666­1 cells. Moreover, the expression level of the proproliferative protein cyclin D1 and antiapoptotic proteins Mcl­1 and Bcl­2 was significantly decreased following transfection with the miR­19b inhibitor. The aforementioned three proteins are downstream transcriptional targets of the activated STAT3 signaling pathway. The results of the present study revealed that inhibition of miR­19b negatively modulated the malignant behavior of NPC cells via the STAT3 signaling pathway. Therefore, miR­19b inhibition may serve as a novel therapeutic target for the treatment of NPC.

Loss of AKR1C1 is a good prognostic factor in advanced NPC cases and increases chemosensitivity to cisplatin in NPC cells.

Cisplatin resistance is one of the main obstacles in the treatment of advanced nasopharyngeal carcinoma (NPC). AKR1C1 is a member of the Aldo-keto reductase superfamily (AKRs), which converts aldehydes and ketones to their corresponding alcohols and has been reported to be involved in chemotherapeutic resistance of multiple drugs. The expression and function of AKR1C1 in NPC have not been reported until now. The aim of this research was to investigate the expression of AKR1C1 and it is role in cisplatin resistance in NPC. AKR1C1 protein expression was detected by immunohistochemistry in human NPC tissues and by Western blot assays in NPC and immortalized nasopharyngeal epithelial cells. The effects of AKR1C1 knock-down by siRNA on proliferation, migration and invasion in NPC cells were evaluated by CCK8, wound healing and transwell assays. To evaluate the effects of AKR1C1 silencing on cisplatin sensitivity in NPC cells, CCK8 assays were used to detect cell proliferation, flow cytometry was used to detect cell cycle distribution, and flow cytometry and DAPI staining were used to detect cell apoptosis. AKR1C1 down-regulation was associated with advanced clinicopathological characters such as larger tumor size, more lymphatic nodes involvement, with metastasis and later clinical stages, while AKR1C1 down-regulation was a good prognostic factor for overall survival (OS) in NPC patients. In vitro study showed that AKR1C1 was not directly involved in the malignant biological behaviours such as proliferation, cell cycle progression and migration of NPC cells, whereas AKR1C1 knock-down could enhance cisplatin sensitivity of NPC cells. These results suggest that AKR1C1 is a potential marker for predicting cisplatin response and could serve as a molecular target to increase cisplatin sensitivity in NPC.