RESUMO
DNA repair genes can be used as prognostic biomarkers in many types of cancer. We aimed to identify prognostic DNA repair genes in patients with gastric cancer (GC) by systematically bioinformatic approaches using web-based database. Global gene expression profiles from altogether 1,325 GC patients' samples from six independent datasets were included in the study. Clustering analysis was performed to screen potentially abnormal DNA repair genes related to the prognosis of GC, followed by unsupervised clustering analysis to identify molecular subtypes of GC. Characteristics and prognosis differences were analyzed among these molecular subtypes, and modular key genes in molecular subtypes were identified based on changes in expression correlation. Multivariate Cox proportional hazard analysis was used to find the independent prognostic gene. Kaplan-Meier method and log-rank test was used to estimate correlations of key DNA repair genes with GC patients'overall survival. There were 57 key genes significantly associated to GC patients' prognosis, and patients were stratified into three molecular clusters based on their expression profiles, in which patients in Cluster 3 showed the best survival (P < 0.05). After a three-phase training, test and validation process, the expression profile of 13 independent key DNA repair genes were identified can classify the prognostic risk of patients. Compared with patients with low-risk score, patients with high risk score in the training set had shorter overall survival (P < 0.0001). Furthermore, we verified equivalent findings by these key DNA repair genes in the test set (P < 0.0001) and the independent validation set (P = 0.0024). Our results suggest a great potential for the use of DNA repair gene profiling as a powerful marker in prognostication and inform treatment decisions for GC patients.
RESUMO
The aberrant expression of long noncoding RNAs (lncRNAs) has been reported frequently in specific cancers, including high-grade serous ovarian cancer (HGSOC). The purpose of the present study was to explore the clinical significance and underlying mechanisms of a significantly dysregulated lncRNA (NEAT1) in HGSOC. Our results showed that elevated NEAT1 expression in human HGSOC specimens correlated with a poor prognosis. Functional experiments demonstrated that knockdown of NEAT1 significantly prohibited ovarian cancer cell proliferation and invasion in vitro and restrained tumor growth in vivo. LIN28B was identified by bioinformatics analysis along with experimental evidence as a direct actor that enhanced NEAT1 stability. A rescue functional assay confirmed that the LIN28B/NEAT1 axis contributed to oncogenic functions in ovarian cancer cells. Moreover, gene expression profile data and dual luciferase reporter assay results demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for miR-506 to promote cell proliferation and migration. Taken together, our results showed that NEAT1, stabilized by LIN28B, promoted HGSOC progression by sponging miR-506. Thus, NEAT1 can be regarded as a vital diagnostic biomarker for HGSOC and a therapeutic target.
Assuntos
Movimento Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , Neoplasias Ovarianas/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Apoptose/genética , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Regulação para Cima/genéticaRESUMO
Recent studies have indicated that miRNA is an important element that regulates gene expression at the post transcriptional level.MiRNAs play important roles in development and progression of chronic disorders of many organs.This review summarizes the recent researches on the association of miRNA with chronic liver diseases.
