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Nasopharyngeal carcinoma (NPC) is a prevalent head and neck tumor which has a high mortality rate in Southeast Asia, especially in Southern China. Cancer susceptibility candidate 2 (CASC2) is a newly identified long non-coding RNA (lncRNA) that has been found to play a suppressive role in several types of tumors. However, the expression and functional role of CASC2 in NPC are still unclear. In the present study, using NPC tissues, cells and transplanted mice, we investigated the mechanism of CASC2-mediated regulation of NPC. We showed that the CASC2 level is reduced in NPC tissues and cells. CASC2 downregulation promoted proliferation and inhibited apoptotic cell death in NPC cells. In contrast, CASC2 upregulation inhibited proliferation and increased apoptosis. There were putative binding sites of microRNA (miR)-18a-5p in the promoter of CASC2. The level of miR-18a-5p was upregulated in NPC tissues and cells. We further confirmed that CASC2 could directly bind with miR-18a-5p and inhibit miR-18a-5p expression, using reporter gene and RNA immunoprecipitation assays. miR-18a-5p suppressed CASC2 upregulation-mediated decrease in proliferation and increase in apoptotic cell death. Bioinformatics predicted the putative binding site of miR-18a-5p in the 3' untranslated region of C-terminal binding protein interacting protein (CtIP)/RBBP8. It was further confirmed that miR-18a-5p could directly bind with RBBP8 and inhibit RBBP8 expression. Downregulation of RBBP8 inhibited the anti-miR-18a-5p-mediated increase in apoptosis and decrease in proliferation. Downregulation of CASC2 increased tumor growth, increased the level of miR-18a-5p and decreased RBBP8 expression in vivo. In summary, CASC2 regulates NPC malignancy through modulation of RBBP8 via sponging miR-18a-5p. Our findings highlight the CASC2/miR-18a-5p/RBBP8 axis in NPC pathogenesis and provide new biomarkers and potential targets for the therapy of NPC. lncRNA CASC2/miR-18a-5p axis regulates the malignant potential of nasopharyngeal carcinoma by targeting RBBP8

Enhancer of zeste homolog 2 (EZH2) is a highly conserved histone methyltransferase, which is overexpressed in different types of cancers such as breast and prostate cancer. It is reported that EZH2 can directly down-regulate RUNX3 by increasing histone H3 methylation. However, the role of EZH2 in the development and progression of laryngeal carcinoma has not yet been investigated, and the relationship between EZH2 and RUNX3 in laryngeal carcinoma is rarely reported. The current study aims to determine the role of EZH2 in the progression of laryngeal carcinoma, and investigate the interaction between EZH2 and the tumor suppressor RUNX3. Our study found that EZH2 is overexpressed in laryngeal carcinoma patients, and silencing EZH2 by EZH2 siRNA significantly inhibited the proliferation of laryngeal carcinoma cells. Besides, we also found that RUNX3 is repressed in laryngeal carcinoma patients. Moreover, RUNX3 as a downstream target protein of EZH2 is up-regulated by EZH2 siRNA accompanied by a decrease in the trimethylation modification pattern of H3K27. RUNX3 siRNA inhibits the decreased proliferation induced by EZH2 siRNA. Furthermore, β-catenin protein expression is down-regulated by EZH2 siRNA and up-regulated by RUNX3 siRNA, and RUNX3 siRNA inhibits the down-regulation effect of EZH2 siRNA on β-catenin protein expression. Additionally, the Wnt/β-catenin activator BIO reverses the inhibitory effect of EZH2 siRNA on Hep-2 cell proliferation. Taken together, our results suggest that EZH2 regulates cell proliferation potentially by targeting RUNX3 through the Wnt/β-catenin signaling pathway in laryngeal carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck cancers, with high mortality and incidence. MicroRNA-26a (miR-26a) is involved in the development and progression of several tumours. However, the roles of miR-26a and its target CKS2 in LSCC progression are not yet clear. The mRNA and protein expression was determined using RT-PCR and Western blotting assay, respectively. Cell proliferation was detected using a Cell Counting kit-8 assay (CCK-8). Transwell assay was used to evaluate cell migration and invasion. Dual-luciferase reporter assay was applied to determine the relationship between miR-26a and CKS2. In addition, a tumour xenograft model in nude mice was established to further determine the effects of miR-26a on tumourigenesis. In this study, we found that miR-26a level was down-regulated in LSCC tissues and cell lines, while CKS2 expression was increased. Cell proliferation, migration, invasion and the expression of MMP2 and MMP9 was suppressed by miR-26a overexpression, but enhanced by inhibition of miR-26a. Dual-luciferase reporter assay demonstrated that CKS2 is a direct target of miR-26a in AMC-HN-8 cells. Overexpression of miR-26a caused a significant reduction in CKS2 expression, and reinforced expression of CKS2 abolished the tumour-suppressive function of miR-26a. Moreover, miR-26a inhibited tumour growth in vivo. Taken together, miR-26a inhibited proliferation and tumourigenesis of LSCC via targeting CKS2 in vitro and in vivo.

Objective: To evaluate the value of 2-dimensional (2D) and 3-dimensional (3D) computed tomography texture analysis (CTTA) models in distinguishing fat-poor angiomyolipoma (fpAML) from chromophobe renal cell carcinoma (chRCC). Methods: We retrospectively enrolled 32 fpAMLs and 24 chRCCs. Texture features were extracted from 2D and 3D regions of interest in triphasic CT images. The 2D and 3D CTTA models were constructed with the least absolute shrinkage and selection operator algorithm and texture scores were calculated. The diagnostic performance of the 2D and 3D CTTA models was evaluated with respect to calibration, discrimination, and clinical usefulness. Results: Of the 177 and 183 texture features extracted from 2D and 3D regions of interest, respectively, 5 2D features and 8 3D features were selected to build 2D and 3D CTTA models. The 2D CTTA model (area under the curve [AUC], 0.811; 95% confidence interval [CI], 0.695-0.927) and the 3D CTTA model (AUC, 0.915; 95% CI, 0.838-0.993) showed good discrimination and calibration ( P > .05). There was no significant difference in AUC between the 2 models ( P = .093). Decision curve analysis showed the 3D model outperformed the 2D model in terms of clinical usefulness. Conclusions: The CTTA models based on contrast-enhanced CT images had a high value in differentiating fpAML from chRCC.

Nasopharyngeal carcinoma (NPC) is frequently seen in Chinese, especially the population that resides in southeast China. Metastasis-associated protein 1 (MTA1) is a chromatin modifier and plays a role in tumor cell metastasis. IQGAP1 is a ubiquitously expressed protein that contributes to cytoskeleton remodeling. This study aimed to investigate the role of MTA1 and IQGAP1 in NPC malignant transformation. MTA1 and IQGAP1 expression in NPC (n = 43) and control tissues (n = 31) were detected using qRT-PCR, immunoblot, and immunohistochemistry. MTA1 was overexpressed in CNE-1 and CNE-2 cell line by pcDNA3.1/MTA1 transfection. Dominant-negative p53 was transfected to inhibit p53 activity. si-IQGAP1 or dominant-negative IQGAP1 (IQGAP1ΔGRD) was used to suppress IQGAP1 activity. Cell proliferation was measured by CKK-8 assay. Cell migration was evaluated by Transwell assay. The results showed that MTA1 and IQGAP1 were highly expressed in NPC tissues compared with the controls. Forced expression of MTA1 accelerated cell proliferation and migration and upregulated IQGAP1 expression in a p53-independent way. Knockdown of IQGAP1 or transfection of dominant-negative IQGAP1 impeded tumor cell proliferation and migration as well as PI3K/Akt signaling induced by MTA1. In conclusion, MTA1 participates in NPC malignant transformation via regulating IQGAP1 expression and PI3K/Akt signaling pathway.