RESUMO
Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor that requires extensive research. Ferroptosis is a unique cell death modality driven by iron-dependent phospholipid peroxidation manifested as an accumulation of lipid-reactive oxygen species. With further understanding of noncoding RNAs (ncRNAs), numerous studies have demonstrated an important regulatory role of ncRNAs in ESCC through ferroptosis, including microRNAs, long ncRNAs, and circular RNAs. These ncRNAs influence the expression of the target gene to regulate ESCC progression by involving the ferroptosis signaling pathway. However, the specific regulatory mechanism of ncRNAs on ferroptosis in ESCC remains largely unknown. This review summarized the current knowledge on the relation between ferroptosis regulators, such as glutathione synthesis/metabolism, Keap1/Nfr2, and p53, by ncRNAs and ESCC. This review also proposed the possible therapeutic approaches for ncRNAs targeting ferroptosis in ESCC. This is the latest and most effective summary of recent research achievements of ncRNAs on ferroptosis in ESCC. These ncRNAs based on ferroptosis merit further investigation in preclinical research of ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ferroptose , MicroRNAs , RNA Longo não Codificante , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genéticaRESUMO
Increasing evidence shows that microRNA (miR)381 is involved in the carcinogenesis and biologic progression of various types of cancer in humans. However, its potential biologic role and mechanism in pancreatic cancer remain to be elucidated. In the present study, the expression and functional role of miR381 in pancreatic cancer were investigated. It was found that miR381 was significantly downregulated in pancreatic cancer tissues and cell lines. The biological functions of miR381 were examined by measuring cell proliferation, migration, invasion and apoptosis in vitro and in vivo. The miR381 target gene and signaling pathway were identified by luciferase activity assay and western blot assay. In vitro experiments confirmed that the enforced expression of miR381 markedly suppressed cell proliferation, migration and invasion, and induced apoptosis in pancreatic cancer cells. By contrast, silencing the expression of miR381 had the opposite effect. In addition, miR381 inhibited xenograft tumor growth in vivo. Furthermore, ETS1 was identified as a direct target of miR381, and western blot analysis showed that miR381 negatively modulated the expression of ETS1. It was also demonstrated that miR381 serves a key role in pancreatic cancer cells through regulating the phosphoinositide 3kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. In conclusion, the data obtained suggested that miR381 mediated cell proliferation, migration and invasion by targeting ETS1, partly through PI3K/AKT/mTOR signaling pathway. These results provide novel insights into understanding the potential effects and molecular mechanism of miR381 on pancreatic cancer. miR381 may serve as a novel potential marker for pancreatic cancer treatment in the future.
Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Proteína Proto-Oncogênica c-ets-1/genética , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias Pancreáticas/patologiaRESUMO
Previous studies have demonstrated that the dysregulation of microRNAs (miRs) is frequently associated with cancer progression. Deregulation of miR106b3p has been observed in various types of human cancer. However, the biological function of miR106b3p in esophageal squamous cell carcinoma (ESCC) remains unclear. Thus, the aim of this study was to investigate the role of miR106b3p in ESCC. In the current study, the results indicated that miR106b3p was upregulated in ESCC cell lines and tissues. An increase in miR106b3p using miR mimics significantly promoted the proliferation of ESCC cells in vitro. Furthermore, the results demonstrated that miR106b3p overexpression promoted migration, invasion and epithelialmesenchymal transition (EMT) of ESCC cells. In addition, zinc and ring finger 3 (ZNRF3) was identified as a target of miR106b3p in ESCC cells, and the ZNRF3 expression level was inversely associated with miR106b3p. It was also demonstrated that miR106b3p has a role in EMT by regulating Wnt/ßcatenin signaling pathway in ESCC. In conclusion, these data suggested that miR106b3p promotes cell proliferation and invasion, partially by downregulating ZNRF3 and inducing EMT via Wnt/ßcatenin signaling in ESCC cells. Thus, miR106b3p and ZNRF3 may be novel molecular targets for the future treatment of ESCC.