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Overwhelming evidence has demonstrated that TSLC1 (tumor suppressor in lung cancer 1), a novel tumor suppressor, is crucially implicated in various biological processes including progression, proliferation and apoptosis during tumorigenesis. However, the exact functions and molecular details of TSLC1 in laryngeal cancer remain ill-defined. Here, the expression of TSLC1 in laryngeal squamous cell carcinoma (LSCC) tissues and cells was detected, and the biological roles of TSLC1 in LSCC cells were investigated. The results showed that expressions of TSLC1 mRNA and protein were significantly reduced in LSCC tissues with low expression in 18 of 85 (21.18 %) and 16 of 85 (18.82 %), respectively. Additionally, statistical analysis revealed a significant correlation of TSLC1 expression with TNM staging and lymph node metastases (P < 0.05), but not related to age, gender and tumor differentiation (P > 0.05). Elevation of TSLC1 level inhibited cell proliferation, reduced cell invasion in vitro and induced cell apoptosis in Hep-2 cells, most importantly, TSLC1 upregulation decreased the level of pAkt, but not changed the level of total Akt in Hep-2 cells. Stepwise investigations demonstrated that overexpression of TSLC1 in Hep-2 cells increased caspase-3 activity and expressions of bax and p21 proteins but decreased the levels of bcl-2, MMP-2 and MMP-9 proteins. These data suggest that TSLC1 may exert essential roles in the progression and development of LSCC, and thus TSLC1 may be a potential molecular target for LSCC treatment.

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Enhanced expression of the ATP-binding cassette (ABC) transporter protein ABC sub-family G member 2 (ABCG2) in cancer stem cells (CSCs) plays a major role in chemotherapeutic drug efflux, which results in therapy failure and tumor relapse. In addition to downregulating apoptosis in CSCs, it has been reported that the transcriptional upregulation of the redox sensing factor Nrf2 is involved in the upregulation of ABCG2 expression and consequent chemoresistance. The current study investigated the presence of cancer stem-like side population (SP) cells from head and neck squamous cell carcinoma (HNSCC) samples, and evaluated the Nrf2 expression profile and multidrug resistance properties of HNSCC stem cells. Fluorescence-activated cell sorting was used for SP cells detection, while reverse transcription-polymerase chain reaction was used for the analysis of Nrf2 expression. The present study identified ~2.1% SP cells present in HNSCC specimens, which were positive for cluster of differentiation (CD)133 expression and displayed significantly elevated messenger RNA expression of Nrf2, compared with non-SP cells. These data suggest that the ABC transporter ABCG2 is highly upregulated in SP cells, and this results in multidrug resistance. In addition, these CD133+ cells underwent rapid proliferation and exhibited high self-renewal and tumorigenic properties. Taken together, the present findings suggest that elevated expression of Nrf2 mediated drug resistance in HNSCC CSCs, which may be one of the causative factors for cancer treatment failure. Therefore, novel anti-cancer drugs that downregulate the Nrf2 signaling pathway could effectively improve the treatment and survival rate of patients with HNSCC.

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.

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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.