ABSTRACT
SUMMARY: The Mettl3/Mettl14 methyltransferase complex installs the most ubiquitous internal mRNA modification- N6-methyladenosine (m6A). The vertebrate retina development is a multi-step process that requires fine-tuning of multiple cellular events, but very little is known about the potential function of Mettl3 and Mettl14 in this process. In this study, we demonstrated the spatio-temporal expression of Mettl3 and Mettl14 during retina development in mouse by quantitative PCR and immunofluorescence staining. We found that these two components of methyltransferase complex could be detected from the beginning of retina development; and the expression of Mettl3 and Mettl14 were gradually restricted to inner nuclear layer (INL) and ganglion cell layer (GCL); Double labeling showed that Mettl3 and Mettl14 had similar expression patterns in mature retinal INL and GCL. Overall, our spatio-temporal expression data provided the foundation for future research on the function of m6A modification in the retina development.
RESUMEN: El complejo Mettl3 / Mettl14 metiltransferasa establece la modificación interna más significativa de ARNm: N6- metiladenosina (m6A). El desarrollo de la retina de los vertebrados es un proceso de varios pasos que requiere múltiples eventos celulares; existe muy poca información sobre la función potencial de Mettl3 y Mettl14 en este proceso. En este estudio, demostramos la expresión espacio-temporal de Mettl3 y Mettl14 durante el desarrollo de la retina en ratón mediante PCR cuantitativa y tinción de inmunofluorescencia. Descubrimos que estos dos componentes del complejo de metiltransferasa podían ser detectados desde el comienzo del desarrollo de la retina; la expresión de Mettl3 y Mettl14 se restringió gradualmente a la capa nuclear interna (INL) y la capa de células ganglionares (GCL); se observó que Mettl3 y Mettl14 tenían patrones de expresión similares en INL y GCL retinianos maduros. En general, nuestros datos de expresión espacio-temporal proporcionan información para futuras investigaciones sobre la función de la modificación de m6A en el desarrollo de la retina.
Subject(s)
Animals , Mice , Retina/embryology , Retina/enzymology , Methyltransferases/metabolism , Staining and Labeling , Immunohistochemistry , Real-Time Polymerase Chain Reaction , Methyltransferases/genetics , Mice, Inbred C57BLABSTRACT
OBJECTIVE@#To investigate the expression of RNA methyltransferase METTL14 in hepatocellular carcinoma (HCC) and its clinical significance.@*METHODS@#Immunohistochemical staining was used to detect the expression of METTL14 in 147 pairs of HCC and adjacent hepatic tissues. According to the scores rated by pathologists, the 147 cases of HCC were divided into high and low METTL14 expression groups. The correlation between the expression of METTL14 and clinicopathological parameters was analyzed, and Kaplan-Meier method was used to analyze the relationship between the expression of METTL14 and the prognosis and survival (including the overall survival and disease-free survival) of the patients with HCC after operation. Univariate analysis and multivariate analysis were carried out to assess the impact of METTL14 expression level on the overall survival and tumor-free survival of the patients after operation using a COX regression model and explore whether METTL14 expression level is an independent prognostic risk factor of the postoperative patients.@*RESULTS@#The expression of METTL14 was significantly lower in HCC tissues than in the adjacent tissues ( < 0.001). METTL14 expression in HCC tissues was significantly correlated with the tumor size (=0.044) and TNM stage (=0.046). A low expression of METTL14 in HCC tissues was significantly correlated with a poor prognosis and a significantly shortened overall survival time and disease-free survival time of the patients ( < 0.05), and was an independent risk factor affecting the overall survival and disease-free survival of HCC patients.@*CONCLUSIONS@#METTL14 may be a new prognostic marker for patients with HCC after hepatectomy.