A novel function for cyclin D1 as a transcriptional role in oncogenesis and tumor development by ChIP-Seq and RNA-Seq.

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102 Background: Cancer is a major public health problem and remains one of the leading causes of death worldwide. Aberrations in cell cycle control is defined as one of the hallmarks of cancer.While cyclin D1 is an essential protein to cell cycle which promote G1 phase into S phase, and frequently overexpressed in many human cancers.Although the participation in cell cycle and tumorigenesis has not been well characterized, new functions have been identified in transgenic mice models, including the transcription of genome, the development of chromosome instability and DNA repair. However, it remains unclear that the function of cyclin D1 independ of involving cell cycle. In this research, our aim is to find the function of cyclin D1 in transcription in human cancers. Methods: We chose the human cervical cancer cell line, C33A as our main research object. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq), to find out the genes differentially expressed in C33A, cyclin D1 knockin C33A and cyclin D1 knockdown C33A. Results: We detected 5590 genes involved in binding with cyclin D1 by ChIP seq, screened 2811 genes upregulation, 2727 genes downregulation in cyclin D1 knockin cells, 2244 genes upregulation, 1738 genes downregulation in cyclin D1 knockdown cells by RNA-seq. Through analysis of the results of ChIP-seq and RNA-seq, we finally identified 422 genes differentially expressed at the RNA level.These genes are highly enriched in Gene Ontology categories and involve in diverse cellular functions via KEGG classification, including translation, replication and repair, signal transduction, cell growth and death. Conclusions: These findings suggested that cyclin D1 can serve both to activate and downregulate gene expression as a transcriptional role directly binding with genome DNA, which means that cyclin D1 may be a key protein during oncogenesis and tumor development.