RASSF1C modulates the expression of a stem cell renewal gene, PIWIL1

Autor: Melissa L Baldwin, Shin-Tai Chen, Xin-Min Li, Robert Aragon, Yousef G. Amaar, Subburaman Mohan, Scott W. Baldwin, Mark E. Reeves
Rok vydání: 2012
Předmět:
Lung Neoplasms
lcsh:Medicine
Apoptosis
RASSF1C
RNA interference
Carcinoma
Non-Small-Cell Lung
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
lcsh:QH301-705.5
Oligonucleotide Array Sequence Analysis
Medicine(all)
ERK1/2
Reverse Transcriptase Polymerase Chain Reaction
Cell Cycle
General Medicine
Cell cycle
Immunohistochemistry
Gene Expression Regulation
Neoplastic
Argonaute Proteins
Benzamides
Neoplastic Stem Cells
RNA Interference
Research Article
Tumor suppressor gene
MAP Kinase Signaling System
Blotting
Western
RASSF1C target genes
Biology
General Biochemistry
Genetics and Molecular Biology
Cell Line
Cell Line
Tumor
medicine
Humans
Gene silencing
lcsh:Science (General)
Lung cancer
Cell Proliferation
Biochemistry
Genetics and Molecular Biology(all)
Cell growth
Gene Expression Profiling
Tumor Suppressor Proteins
lcsh:R
medicine.disease
Gene expression profiling
PIWIL1
lcsh:Biology (General)
Cell culture
Cancer research
Gene expression
lcsh:Q1-390
Zdroj: BMC Research Notes, Vol 5, Iss 1, p 239 (2012)
BMC Research Notes
ISSN: 1756-0500
DOI: 10.1186/1756-0500-5-239
Popis: Background RASSF1A and RASSF1C are two major isoforms encoded by the Ras association domain family 1 (RASSF1) gene through alternative promoter selection and mRNA splicing. RASSF1A is a well established tumor suppressor gene. Unlike RASSF1A, RASSF1C appears to have growth promoting actions in lung cancer. In this article, we report on the identification of novel RASSF1C target genes in non small cell lung cancer (NSCLC). Methods Over-expression and siRNA techniques were used to alter RASSF1C expression in human lung cancer cells, and Affymetrix-microarray study was conducted using NCI-H1299 cells over-expressing RASSF1C to identify RASSF1C target genes. Results The microarray study intriguingly shows that RASSF1C modulates the expression of a number of genes that are involved in cancer development, cell growth and proliferation, cell death, and cell cycle. We have validated the expression of some target genes using qRT-PCR. We demonstrate that RASSF1C over-expression increases, and silencing of RASSF1C decreases, the expression of PIWIL1 gene in NSCLC cells using qRT-PCR, immunostaining, and Western blot analysis. We also show that RASSF1C over-expression induces phosphorylation of ERK1/2 in lung cancer cells, and inhibition of the MEK-ERK1/2 pathway suppresses the expression of PIWIL1 gene expression, suggesting that RASSF1C may exert its activities on some target genes such as PIWIL1 through the activation of the MEK-ERK1/2 pathway. Also, PIWIL1 expression is elevated in lung cancer cell lines compared to normal lung epithelial cells. Conclusions Taken together, our findings provide significant data to propose a model for investigating the role of RASSF1C/PIWIL1 proteins in initiation and progression of lung cancer.
Databáze: OpenAIRE
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