RESUMEN
OBJECTIVE@#In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma (HNSCC)-associated long noncoding RNAs (lncRNAs), and to discover potential lncRNA prognostic biomarkers for HNSCC based on next-generation RNA-seq.@*METHODS@#RNA-seq data of 546 samples from patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA), including 43 paired samples of tumor tissue and adjacent normal tissue. An integrated analysis incorporating differential expression, weighted gene co-expression networks, functional enrichment, clinical parameters, and survival analysis was conducted to discover HNSCC-associated lncRNAs. The function of CYTOR was verified by cell-based experiments. To further identify lncRNAs with prognostic significance, a multivariate Cox proportional hazard regression analysis was performed. The identified lncRNAs were validated with an independent cohort using clinical feature relevance analysis and multivariate Cox regression analysis.@*RESULTS@#We identified nine HNSCC-relevant lncRNAs likely to play pivotal roles in HNSCC onset and development. By functional enrichment analysis, we revealed that CYTOR might participate in the multistep pathological processes of cancer, such as ribosome biogenesis and maintenance of genomic stability. CYTOR was identified to be positively correlated with lymph node metastasis, and significantly negatively correlated with overall survival (OS) and disease free survival (DFS) of HNSCC patients. Moreover, CYTOR inhibited cell apoptosis following treatment with the chemotherapeutic drug diamminedichloroplatinum (DDP). HCG22, the most dramatically down-regulated lncRNA in tumor tissue, may function in epidermis differentiation. It was also significantly associated with several clinical features of patients with HNSCC, and positively correlated with patient survival. CYTOR and HCG22 maintained their prognostic values independent of several clinical features in multivariate Cox hazards analysis. Notably, validation either based on an independent HNSCC cohort or by laboratory experiments confirmed these findings.@*CONCLUSIONS@#Our transcriptomic analysis suggested that dysregulation of these HNSCC-associated lncRNAs might be involved in HNSCC oncogenesis and progression. Moreover, CYTOR and HCG22 were confirmed as two independent prognostic factors for HNSCC patient survival, providing new insights into the roles of these lncRNAs in HNSCC as well as clinical applications.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diferenciación Celular , Células Cultivadas , Perfilación de la Expresión Génica , Neoplasias de Cabeza y Cuello/patología , Modelos de Riesgos Proporcionales , ARN Largo no Codificante/fisiología , Ribosomas/fisiología , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
The open reading frame (ORF) encoding curcin 2 was cloned from total genomic and cDNA of Jatropha curcas leaves, which were treated by drought, temperature stress and fungal infection, by polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR amplification. The ORF has 927 bp that encodes a precursor protein of 309 amino acid residues. There are high similarities with curcin and the conserved domain of ribosome inactivating proteins (RIPs). Antiserum to curcin recognized one band of 32 kDa on Western blot of the leaves treated by temperature stresses at 4 degree C and 50 degree C and by fungal infections of Pestalotia funerea, Curvularia lunata (Walk) Boed, Gibberelle zeae (Schw.) Petch. Two bands of 32 kDa and 65 kDa were recognized on Western blot of the leaves treated by 10--40 percent polyethylene glycol (PEG). In addition, the 32 kDa band is nearly the molecular weight of curcin 2. This finding suggests that the protein of 32 kDa should be related to curcin 2. The presence of this protein molecular marker under stresses may provide an experimental foundation to study the stress proteins in J. curcas.
Asunto(s)
Secuencia de Aminoácidos , Secuencia de Bases , Secuencia Conservada , ADN Complementario/química , ADN de Plantas/química , Regulación de la Expresión Génica de las Plantas/fisiología , Jatropha/metabolismo , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Proteínas de Plantas/biosíntesis , Ribosomas/fisiología , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoRESUMEN
Se estudian los perfiles ribosomales en un miometrio normal en menopausia, y tres miometrios normales al final del embarazo. Se estudian tambien estos perfiles ribosomales en tres miometrios patologicos en adenomiosis, en miomatosis y en sarcomatosis. La mayor actividad en sintesis proteica miometrial fue revelada en orden decreciente por la adenomiosis, la sarcomatosis, la miomatosis, el embarazo a termino y finalmente la menopausia.