ABSTRACT
The long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3), a tumor suppressor, is critical for the carcinogenesis and progression of different cancers, including hepatocellular carcinoma (HCC). To date, the roles of lncRNA MEG3 in HCC are not well illustrated. Therefore, this study used western blot and qRT-PCR to evaluate the expression of MEG3, miR-9-5p, and Sex determining Region Y-related HMG-box 11 (SOX11) in HCC tissues and cell lines. RNA pull-down and luciferase reporter assay were used to evaluate these molecular interactions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry detected the viability and apoptosis of HCC cells, respectively. The results showed that MEG3 and SOX11 were poorly expressed but miR-9-5p was highly expressed in HCC. The expression levels of these molecules suggested a negative correlation between MEG3 and miR-9-5p and a positive correlation with SOX11, confirmed by Pearson's correlation analysis and biology experiments. Furthermore, MEG3 could combine with miR-9-5p, and SOX11 was a direct target of miR-9-5p. Moreover, MEG3 over-expression promoted cell apoptosis and growth inhibition in HCC cells through sponging miR-9-5p to up-regulate SOX11. Therefore, the interactions among MEG3, miR-9-5p, and SOX11 might offer a novel insight for understanding HCC pathogeny and provide potential diagnostic markers and therapeutic targets for HCC.
Subject(s)
Humans , Male , Female , Middle Aged , Carcinoma, Hepatocellular/genetics , MicroRNAs/genetics , SOXC Transcription Factors/genetics , RNA, Long Noncoding/genetics , Liver Neoplasms/genetics , Transfection , Gene Expression Regulation, Neoplastic , Transcriptional Activation , Up-Regulation , Apoptosis/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , MicroRNAs/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , SOXC Transcription Factors/metabolism , Real-Time Polymerase Chain Reaction , RNA, Long Noncoding/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Neoplasm StagingABSTRACT
Activity of the human long interspersed nuclear elements-1 (LINE-1) retrotransposon occurs mainly in early embryonic development and during hippocampal neurogenesis. SOX-11, a transcription factor relevant to neuronal development, has unknown functions in the control of LINE-1 retrotransposon activity during neuronal differentiation. To study the dependence of LINE-1 activity on SOX-11 during neuronal differentiation, we induced differentiation of human SH-SY5Y neuroblastoma cells and adult adipose mesenchymal stem cells (hASCs) to a neuronal fate and found increased LINE-1 activity. We also show that SOX-11 protein binding to the LINE-1 promoter is higher in differentiating neuroblastoma cells, while knock-down of SOX-11 inhibits the induction of LINE-1 transcription in differentiating conditions. These results suggest that activation of LINE-1 retrotransposition during neuronal differentiation is mediated by SOX-11.
Subject(s)
Cell Differentiation/genetics , Long Interspersed Nucleotide Elements/genetics , Neurons/metabolism , SOXC Transcription Factors/genetics , Adipose Tissue/cytology , Cell Line, Tumor , Cells, Cultured , Gene Expression Regulation , HEK293 Cells , HeLa Cells , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Neurogenesis/genetics , Neurons/cytology , RNA Interference , SOXC Transcription Factors/metabolismABSTRACT
SOX11, belonging to the family of genes SOXC, is a transcript factor involved in the embryonic neurogenesis and tissue remodeling, also participating in the control of cell proliferation. Its role in lymphomagenesis still remains unknown. Recent studies have shown aberrant SOX11 nuclear protein expression as well as mRNA levels in patients with mantle cell lymphoma (MCL). Although the majority of these lymphomas have an aggressive clinical course, there is a subgroup of patients with an indolent clinical evolution, suggesting a greater heterogeneity of this disease. Currently, there are contradictions regarding the association of SOX11 gene expression and outcome in MCL, while some authors have related the lack of SOX11 expression with good prognosis, others find it associated with an adverse clinical course. This difference in the gene expression could be associated to epigenetic mechanisms such as modifications at the histone level and DNA methylation that would allow the aberrant expression of this gene in some lymphoid neoplasias, including LCM. More knowledge of gene SOX11 in LCM will lead to a greater understanding of those mechanisms involved in the pathogenesis and progression of this lymphoma, also the involvement of SOX11 in these processes.
Subject(s)
Lymphoma, Mantle-Cell/genetics , SOXC Transcription Factors/genetics , Biomarkers, Tumor/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , SOXC Transcription Factors/physiologyABSTRACT
El gen SOX11, perteneciente a la familia de genes SOXC, es un factor de transcripción involucrado en la neurogénesis embrionaria y el remodelado tisular, participando asimismo en el control de la proliferación celular. Su rol en la linfomagénesis es desconocido. Estudios recientes han mostrado expresión proteica nuclear aberrante y sobreexpresión de los niveles de transcripto de SOX11 en pacientes con linfoma de células del manto (LCM). Si bien la mayoría de estos linfomas presentan un curso clínico agresivo, existe un subgrupo de pacientes con enfermedad indolente, sugiriendo una mayor heterogeneidad de esta patología. Actualmente, existen contradicciones respecto de la asociación entre la expresión del gen SOX11 y la evolución clínica del LCM; mientras algunos autores relacionan la ausencia de expresión de SOX11 con buen pronóstico, otros lo encuentran asociado a un curso clínico adverso. Esta diferencia en la expresión estaría relacionada a mecanismos epigenéticos, metilación del ADN y modificaciones a nivel de histonas, que permitirían la expresión aberrante de este gen en algunas neoplasias linfoides, incluyendo LCM. La profundización del conocimiento del gen SOX11 en LCM hará factible, sin duda, lograr una mayor comprensión de los mecanismos involucrados en la patogénesis y/o progresión de este linfoma, así como del rol de SOX11 en estos procesos.(AU)
SOX11, belonging to the family of genes SOXC, is a transcript factor involved in the embryonic neurogenesis and tissue remodeling, also participating in the control of cell proliferation. Its role in lymphomagenesis still remains unknown. Recent studies have shown aberrant SOX11 nuclear protein expression as well as mRNA levels in patients with mantle cell lymphoma (MCL). Although the majority of these lymphomas have an aggressive clinical course, there is a subgroup of patients with an indolent clinical evolution, suggesting a greater heterogeneity of this disease. Currently, there are contradictions regarding the association of SOX11 gene expression and outcome in MCL, while some authors have related the lack of SOX11 expression with good prognosis, others find it associated with an adverse clinical course. This difference in the gene expression could be associated to epigenetic mechanisms such as modifications at the histone level and DNA methylation that would allow the aberrant expression of this gene in some lymphoid neoplasias, including LCM. More knowledge of gene SOX11 in LCM will lead to a greater understanding of those mechanisms involved in the pathogenesis and progression of this lymphoma, also the involvement of SOX11 in these processes.(AU)
ABSTRACT
El gen SOX11, perteneciente a la familia de genes SOXC, es un factor de transcripción involucrado en la neurogénesis embrionaria y el remodelado tisular, participando asimismo en el control de la proliferación celular. Su rol en la linfomagénesis es desconocido. Estudios recientes han mostrado expresión proteica nuclear aberrante y sobreexpresión de los niveles de transcripto de SOX11 en pacientes con linfoma de células del manto (LCM). Si bien la mayoría de estos linfomas presentan un curso clínico agresivo, existe un subgrupo de pacientes con enfermedad indolente, sugiriendo una mayor heterogeneidad de esta patología. Actualmente, existen contradicciones respecto de la asociación entre la expresión del gen SOX11 y la evolución clínica del LCM; mientras algunos autores relacionan la ausencia de expresión de SOX11 con buen pronóstico, otros lo encuentran asociado a un curso clínico adverso. Esta diferencia en la expresión estaría relacionada a mecanismos epigenéticos, metilación del ADN y modificaciones a nivel de histonas, que permitirían la expresión aberrante de este gen en algunas neoplasias linfoides, incluyendo LCM. La profundización del conocimiento del gen SOX11 en LCM hará factible, sin duda, lograr una mayor comprensión de los mecanismos involucrados en la patogénesis y/o progresión de este linfoma, así como del rol de SOX11 en estos procesos.
SOX11, belonging to the family of genes SOXC, is a transcript factor involved in the embryonic neurogenesis and tissue remodeling, also participating in the control of cell proliferation. Its role in lymphomagenesis still remains unknown. Recent studies have shown aberrant SOX11 nuclear protein expression as well as mRNA levels in patients with mantle cell lymphoma (MCL). Although the majority of these lymphomas have an aggressive clinical course, there is a subgroup of patients with an indolent clinical evolution, suggesting a greater heterogeneity of this disease. Currently, there are contradictions regarding the association of SOX11 gene expression and outcome in MCL, while some authors have related the lack of SOX11 expression with good prognosis, others find it associated with an adverse clinical course. This difference in the gene expression could be associated to epigenetic mechanisms such as modifications at the histone level and DNA methylation that would allow the aberrant expression of this gene in some lymphoid neoplasias, including LCM. More knowledge of gene SOX11 in LCM will lead to a greater understanding of those mechanisms involved in the pathogenesis and progression of this lymphoma, also the involvement of SOX11 in these processes.