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.

F factor plasmid-mediated Epstein-Barr virus genome introduction establishes an EBV positive NPC cell model.

BACKGROUND: Most Epstein-Barr virus (EBV)-positive cells lose the EBV episomes upon prolonged propagation. PURPOSE: The purposes of this study were to establish a simple cell model for nasopharyngeal carcinoma (NPC) research by introducing a plasmid with the EBV genome into NPC cells and then to investigate the resulting changes in malignant biological behaviour and NPC-associated signalling pathways. METHODS: HONE1 NPC cells were transfected with F-factor plasmids including the EBV genome (HONE1-EBV cells). Then cell proliferation, migration, cell cycle distribution and apoptosis were evaluated in vitro by using CCK8, transwell and flow cytometry assays respectively. EBV-encoded proteins and cell signal tranducting proteins were detected by western blot assays. EBV-encoded RNAs were detected by in situ hybridization. EBV particles were assayed by transmission electron microscope (TEM). The morphology of cells were detected by immunofluorescence assays for alpha-tubulin. RESULTS: Latent membrane protein 1 (LMP1), latent membrane protein 2A (LMP2A), Epstein-Barr nuclear antigen 1 (EBNA1) and EBV-encoded small RNAs (EBERs) were successfully expressed in HONE1-EBV cells. No EBV particles were founded by TEM. Introduction of the EBV genome significantly promoted proliferation, cell cycle progression and migration and inhibited apoptosis in HONE1 cells. Immunofluorescence assays showed that the morphology of HONE1-EBV cells changed into spindle. Furthermore, EBV genome introduction significantly inhibited the JAK/STAT signalling pathway, while it activated the PI3K-AKT and NF-κB signalling pathways in HONE1 cells. CONCLUSION: These findings suggest that F-factor plasmid-mediated EBV genome introduction was successful in constructing an EBV positive cell model, which showed deteriorated biological behavior and activated NPC-associated signalling pathways. This model can serve as a good tool for studying EBV in NPC, but the subtle differences in cancer-associated pathways must be considered.

Sarcomatoid Chromophobe Renal Cell Carcinoma: A Case Report and Review of the Literature.

BACKGROUND Sarcomatoid renal cell carcinoma is not a distinct histologic entity transformed from different subtypes of renal cell carcinoma. The sarcomatoid transformation was accepted as the result of dedifferentiation of the primary tumor. Here we present a case of sarcomatoid chromophobe renal cell carcinoma and review the clinicopathological characteristics of sarcomatoid chromophobe renal cell carcinoma. CASE REPORT A 63-year-old female complained of painless gross hematuria for 3 months. Routine urine test showed that urinary protein was ++ and white blood cells were +++; serum CA153 was moderately elevated at 71.08 U/mL (normal <28 U/mL). Ultrasonography and a computed tomography scan showed a mass in the lower pole of the right kidney, measuring 13.4×15.4×11.4 cm. She underwent a right radical nephrectomy with lymph nodes dissection under general anesthetic. There was no evidence of recurrence and lymphadenopathy 12 months after surgery. CONCLUSIONS Sarcomatoid chromophobe renal cell carcinoma is an uncommon tumor characterized by a biphasic tumor with both classical epithelial components and sarcomatoid components. The prognosis of sarcomatoid chromophobe renal cell carcinoma is worse than classical chromophobe renal cell carcinoma. It is important to recognize that sarcomatoid change of chromophobe renal cell carcinoma has the potential to behave aggressively and to metastasize.