ABSTRACT
BACKGROUND: The prevalence of laryngeal squamous cell carcinoma (LSCC) is increasing, and it poses a significant threat to human health; therefore, identifying specific targets for LSCC remains crucial. METHODS: Bioinformatics analysis was used to compare the different expression genes expressed in LSCC. Immunohistochemical assay and western blotting were used to analysis protein expression. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)((4,5 Dimethyl thiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide)4,5 Dimethyl thiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) and 5-ethynyl 2'-deoxyuridine (Edu) assay. Flow cytometry was used to measure the cell cycle. Cell migration was measured by wound healing assay and transwell assay. RESULTS: Our analysis revealed 36 upregulated and 65 downregulated differentially expressed genes (DEGs) when comparing LSCC tumors to adjacent tissues, with cornulin (CRNN) identified as a key hub gene connecting these DEGs. We observed a consistent downregulation of CRNN expression in LSCC cell lines and tissues and was associated with poor patient survival and the tumor microenvironment. CRNN overexpression was found to significantly inhibit cell growth, cell cycle progression, migration and invasion, while CRNN knockdown had the opposite effects. Additionally, in vivo experiments demonstrated that CRNN overexpression suppressed tumor growth in nude mice. CONCLUSIONS: CRNN functions as a potential tumor suppressor and regulates important aspects of LSCC, providing valuable insights into the role of CRNN in LSCC pathogenesis and potential for targeted therapeutic interventions.
Subject(s)
Carcinoma, Squamous Cell , Laryngeal Neoplasms , MicroRNAs , Squamous Cell Carcinoma of Head and Neck , Animals , Humans , Mice , Bromides/metabolism , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/metabolism , Laryngeal Neoplasms/pathology , Mice, Nude , MicroRNAs/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , Tumor MicroenvironmentABSTRACT
Nasopharyngeal carcinoma (NPC) is the most common aggressive squamous cell carcinoma in head and neck cancers. Although advanced radiochemotherapy has been applied, the prognosis of NPC patients still remains poor due to the regional relapse and distant metastasis. Polyphyllin I (PP I) is extracted from natural herb Paris polyphylla that has been widely used in cancer treatment and long non-coding RNA (lncRNA) has been reported to play a key role in the anti-tumour activity of PP I. In this study, it has been found that PP I inhibited the proliferation and induced apoptosis of NPC cells in a dose-dependent manner. A higher level of lncRNA regulator of reprogramming (ROR) expression was detected in NPC cell lines compared with normal nasopharyngeal cell line and PP I must significantly down-regulate the expression level of lncRNA ROR. LncRNA ROR/P53 signalling was essential for PP I-suppressed NPC progression. These data indicated that PP I suppressed tumour growth and induced apoptosis of NPC in vitro and in vivo through down-regulation of lncRNA-ROR, subsequently upregulating of P53 signalling. LncRNA ROR may be a potential therapeutic target and PP I would be a promising candidate for NPC treatment.
Subject(s)
Diosgenin/analogs & derivatives , Nasopharyngeal Carcinoma/drug therapy , RNA, Long Noncoding/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacology , Diosgenin/administration & dosage , Diosgenin/pharmacology , Down-Regulation/drug effects , Drug Delivery Systems , Gene Expression Regulation/drug effects , Male , Mice , Mice, Nude , Neoplasms, Experimental , Signal TransductionABSTRACT
BACKGROUND: It has been reported that ribophorin II (RPN2) expression is increased in many cancers, but the role of RPN2 in nasopharyngeal carcinoma (NPC) remains unclear. PATIENTS AND METHODS: This study found that the expression of RPN2 is increased dramatically in NPC tissues of patients compared with that in the adjacent normal tissues. This study attempted at understanding the effect of siRNA-RPN2 treatment on the migration and invasion of NPC cell lines CNE2 and HNE1. RESULTS: RT-PCR and Western blotting showed that RPN2 was highly expressed in CNE2 and HNE1 cells. siRNA-RPN2 treatment significantly inhibited cell viability at 24 and 48 h compared with the control group. Results of the transwell assay showed that, compared to the control groups, migration and invasion of the cells treated with siRNA-RPN2 decreased markedly. In addition, compared to the control groups, caspase-3, caspase-9, and E-cadherin expression levels increased and MMP 2 expression decreased significantly in the siRNA-RPN2-treated group. Phosphorylation of AKT and PI3K was also inhibited after siRNA-RPN2 treatment. CONCLUSION: siRNA-RPN2 can effectively inhibit the invasion and migration of human NPC cells via AKT/PI3K signaling. This can serve as a novel strategy for NPC treatment.
