Oncogene c‐fos and mutant R175H p53 regulate expression of Nucleophosmin implicating cancer manifestation

Abstract

Nucleophosmin (NPM1) is a nucleolar protein that is frequently overexpressed in various types of solid tumors. NPM1 is involved in several cellular processes that might contribute significantly to the increased proliferation potential of cancers. Previous reports suggest that NPM1 expression is highly increased in response to mitogenic and oncogenic signals, the mechanisms of which have not been elucidated extensively. Using constructs incorporating different fragments of the NPM1 promoter upstream to a Luciferase reporter gene, we have identified the minimal promoter of NPM1 and candidate transcription factors regulating NPM1 promoter activity by luciferase reporter assays. We have validated the roles of a few candidate factors at the transcriptional and protein level by quantitative reverse transcriptase PCR, immunoblotting and immunohistochemistry, and explored the mechanism of regulation of NPM1 expression using immunoprecipitation and chromatin immunoprecipitation assays. We show here that the expression of NPM1 is regulated by transcription factor c-fos, a protein that is strongly activated by growth factor signals. In addition, mutant p53 (R175H) overexpression also enhances NPM1 expression possibly through c-myc and c-fos. Moreover, both c-fos and mutant p53 are overexpressed in oral tumor tissues that showed NPM1 overexpression. Collectively, our results suggest that c-fos and mutant p53 R175H positively regulate NPM1 expression, possibly in synergism, that might lead to oncogenic manifestation.

P53-R273H mutation enhances colorectal cancer stemness through regulating specific lncRNAs

“…Mutant p53 have been found to gain of function in tumor malignancy, and different types of mutation have diverse functions in cancer development, which further explains the gain-of-function of mutant p53. Previous studies on p53-R175H or p53-R248W have mainly focused on their effects on tumor propagation [38, 39]. P53-R273H has been shown to induce drug resistance through downregulating procaspase-3 levels [40] and promoting chronic inflammation and inflammation-associated cancer [41].…”

SOCS2 is a potential prognostic marker that suppresses the viability of hepatocellular carcinoma cells

“…The top five highest value nodes were serine/threonine-protein kinase 1, V-Jun avian sarcoma virus 17 oncogene homolog, mitogen-activated protein kinase 8, mammalian target of rapamycin and early growth response 1, all of which have been reported to be involved in the development of multiple tumors (26)(27)(28)(29). The top five highest value DEGs were Fos proto-oncogene (FOS), SOCS2, forkhead transcription factor 1 (FOXO1), growth arrest and DNA damage inducible β (GADD45B) and cysteine rich angiogenic inducer 61 (CYR61), which are also considered to play critical roles in tumor progression (30)(31)(32)(33)(34). GO and KEGG enrichment analyses of the DEGs were performed using DAVID.…”

Classic and Variants APLs, as Viewed from a Therapy Response

“…Indeed, basal RARA expression is low and the translocations not only fuse two genes, but also put the downstream gene under the control of the upstream gene promoter. In some cases, such as NPM1, these are very strong promoters [163], predicting supra-physiological levels of X-RARA expression, in contrast to PML-RARA. This may explain why some of these patients responded well to ATRA.…”