E2F-1 RNomics is critical for reprogramming of cancer cells to quiescent state.
The discovery of cooperativity between pRB and E2F greatly prompted various investigators to find how E2F biology contributes to oncogenesis. Although E2F family of transcription factors have been linked to proliferation, apoptosis and differentiation, yet no heed has been paid to understand the role of E2F biology in cellular quiescence. To understand the functional RNomics (regulation of gene transcription through RNA interference) of E2F-1 gene, 2 cancer cell lines, such as Jurkat exhibiting E2F-1 gene overamplification and Hela-229 exhibiting intrinsic downregulation of E2F-1 gene expression, were used in our study. E2F-1 gene knockdown via siRNA within Jurkat cells resulted in upregulation of genes characteristic of quiescence both translationally and transcriptionally, which was accompanied by downregulation of genes at both translational and transcriptional level involved in cell cycle progression and apoptosis. This genomic phenomenon also translated into ultrastructural and phenotypic features typical of quiescent state. These observed results in Jurkat cells were simulated by upregulation of E2F-1 gene in Hela-229 cells through the downregulation of miR 17-5p. This E2F-1-regulated pathway explained as to how Jurkat cells entered exclusively into quiescent state when E2F-1 was downregulated in these cells and how Hela-229 cells proliferate vigorously when E2F-1 was upregulated in such cells. Here, we propose a gene-regulatory pathway which the cell might be using in its entry into either quiescent or proliferative states. Furthermore, this pathway may be useful in designing strategies for the treatment of cancer in general and acute lymphoblastic leukemia in particular.
Mehrotra
Aanchal
A
Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
Joshi
Kusum
K
Kaul
Deepak
D
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors