RESUMEN
We previously reported the oncogenic function of miR-92a in colorectal cancer. This study identified that miR-92a was upregulated in chemoresistant colorectal cancer cells and tissues. Ectopic expression of miR-92a conferred resistance to 5-fluorouracil-induced apoptosis in vitro, while antagomiR-92a significantly enhanced chemosensitivity in vivo. Moreover, Overexpression of miR-92a promoted the tumor sphere formation and the expression of stem cell markers. MiR-92a overexpression also displayed higher tumourigenesis in vivo. Furthermore, we demonstrated that miR-92a upregulates the Wnt/ß-catenin signaling activity via directly targeting KLF4, GSK3ß and DKK3, which are multiple level negative regulators of the Wnt/ß-catenin signaling cascade. In addition, our results indicate IL-6/STAT3 pathway increases miR-92a expression by directly targeting its promoter, resulting in Wnt/ß-catenin signaling activation and consequent promotion of stem-like phenotypes of colorectal cancer cells. Our present results suggest the essential role of IL-6/STAT3/miR-92a/Wnt/ß-catenin pathway in regulating the stem cell-like traits of colorectal cancer cells and provide a potential target for colorectal cancer therapy.
RESUMEN
MicroRNAs have recently emerged as regulators of many biological processes including cell proliferation, development and differentiation. This study identified that miR-22 was statistically decreased in colorectal cancer clinical specimens and highly metastatic cell lines. Moreover, low miR-22 expression was associated with tumor metastasis, advanced clinical stage and relapse. Consistent with clinical observations, miR-22 significantly suppressed the ability of colorectal cancer cells to growth and metastasize in vitro and in vivo. Sp1 was validated as a target of miR-22, and ectopic expression of Sp1 compromised the inhibitory effects of miR-22. In addition, Sp1 repressed miR-22 transcription by binding to the miR-22 promoter, hence forming a negative feedback loop. Further study has shown that miR-22 suppresses the activity of PTEN/AKT pathway by Sp1. Our present results implicate the newly indentified miR-22/Sp1/PTEN/AKT axis might represent a potential therapeutic target for colorectal cancer.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Factor de Transcripción Sp1/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Humanos , Ratones , Modelos Biológicos , Metástasis de la Neoplasia , Fosfohidrolasa PTEN/metabolismo , Pronóstico , Regiones Promotoras Genéticas , Unión Proteica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Recurrencia , Transducción de Señal , Factor de Transcripción Sp1/genéticaRESUMEN
BACKGROUND: A systematic review and meta-analysis of all available publications was performed to evaluate the diagnostic accuracy of percutaneous transthoracic needle biopsy (PTNB) using a C-Arm Cone-Beam CT (CBCT) system in patients with lung nodules. MATERIAL/METHODS: Thedatabases of PUBMED, OVID, EBSCO, EMBASE, and China National Knowledge Infrastructure (CNKI) were systematically searched for relevant original articles on the diagnostic accuracy of CBCT-guided PTNB for the diagnosis of nodules in the lungs. Diagnostic indices including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and diagnostic score (DS) were calculated. Moreover,summary receiver operating characteristic curves (SROC) were constructed with Stata (version 13.0), Rev Man (version 5.3), and Meta-disc (version 1.4) software. Other clinical indices such as incidence of complications were also recorded. RESULTS: Eight studies met the inclusion and exclusion criteria for the meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, DS, and SROC with 95% confidence intervals were 0.96 (0.93-0.98), 1.00 (0.91-1.00), 711.15 (9.48-53325.89), 0.04 (0.02-0.07), 16585.29 (284.88-9.7e+05), 9.72 (5.65-13.78), and 0.99 (0.97-0.99), respectively. The incidence of pneumothorax and hemorrhage was 10-29.27% and 1.22-47.25%, respectively. CONCLUSIONS: CBCT-guided PTNB has an acceptable rate of complications and is associated with a reasonable radiation exposure. Moreover, it is a highly accurate and safe technique for the diagnosis of lung nodules and can be recommended to be used in routine clinical practice.