Expression of alternatively spliced FGF-2 antisense RNA transcripts in the central nervous system: regulation of FGF-2 mRNA translation

Li, Audrey W.; Murphy, Paul R.

doi:10.1016/s0303-7207(00)00209-4

Cited by 57 publications

(51 citation statements)

References 41 publications

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“…We showed here that, although GFG protein was localized to the nucleus of occasional cells of the proliferative basal/parabasal layers of normal esophageal squamous epithelium, GFG protein was detected in 63% of esophageal tumor cell nuclei. Although we cannot rule out the possibility that the protective effect of FGF-AS is mediated by actions of GFG, the lack of association between GFG protein expression and recurrence or survival suggests that the protective effect is likely to be the result of the known post-transcriptional effects of the antisense RNA on FGF-2 expression (11).…”

Section: Discussionmentioning

confidence: 90%

“…The inverse association of FGF-2 and FGF-AS mRNA levels in avian, rat, and human tissues, tumors, and cell lines has tended to corroborate the hypothesis that FGF-AS negatively regulates FGF-2 expression (14, 17, 35 -37). We have shown previously that transfection and overexpression of FGF-AS in rat glioma cells resulted in post-transcriptional suppression of FGF-2 and inhibition of cell proliferation (11). It is therefore possible that the expression of the FGF-AS mRNA under basal conditions is sufficient to suppress FGF-2 gene expression by transcriptional or post-transcriptional mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Reverse transcription-PCR was used to study FGF-2 and FGF-AS mRNA expression [normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH)] in tumors, relative to matched histologically normal esophageal epithelia (internal control), using techniques reported previously (11). RNA was extracted from each esophageal tissue specimen using the TRIzol reagent (Life Technologies, Burlington, Ontario, Canada) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Although the control of FGF-2 expression is poorly understood, one intriguing possibility is regulation by an endogenous antisense RNA, FGF-AS (11). Like the majority of cis-antisense transcript pairs characterized to date, FGF-2 and FGF-AS are transcribed as 3V-to-3V overlaps; the sense and antisense RNAs are fully complementary over extensive regions of their 3V untranslated regions and have been shown to form stable double-stranded RNA duplexes in vivo (12).…”

mentioning

confidence: 99%

“…The inverse association of FGF-2 and FGF-AS mRNA expression observed in a variety of species supports the hypothesis that FGF-2 may be regulated by interaction with the antisense RNA (14 -18). We have shown recently that forced overexpression of the FGF-AS mRNA can effectively suppress FGF-2 levels in stably transfected cells in vitro (11). In addition to its putative role as a regulatory RNA, FGF-AS also encodes the protein GFG/NUDT6, a member of the nudix family of nucleoside phosphohydrolases (19,20).…”

mentioning

confidence: 99%

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Basic Fibroblast Growth Factor (FGF-2) Overexpression Is a Risk Factor for Esophageal Cancer Recurrence and Reduced Survival, which Is Ameliorated by Coexpression of the FGF-2 Antisense Gene

Barclay¹,

Li²,

Geldenhuys³

et al. 2005

Clinical Cancer Research

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Purpose:The basic fibroblast growth factor (FGF-2) gene is bidirectionally transcribed to generate overlapping sense and antisense (FGF-AS) mRNAs. FGF-AS has been implicated in the posttranscriptional regulation of FGF-2 expression. The aim of this study was to characterize FGF-2 and FGF-AS in esophageal cancer and to correlate their expression with clinicopathologic findings and outcome. Experimental Design: Reverse transcription-PCR was used to study FGF-2 and FGF-AS mRNA expression (normalized to glyceraldehyde-3-phosphate dehydrogenase) in 48 esophageal cancers relative to matched histologically normal esophageal epithelia (internal control). We used Cox proportional hazards analysis to calculate hazard ratios for recurrence and survival of patients with underexpression relative to the overexpression of FGF-2 and/or FGF-AS. Results: Overexpression of FGF-2 mRNA, by comparison with tumors underexpressing FGF-2, was associated with significantly increased risk for tumor recurrence (hazard ratio, 3.80; 95% confidence interval, 1.64-8.76) and reduced overall survival (hazard ratio, 2.11; 95% confidence interval, 1.0-4.58). When the effects of FGF-2 and FGF-AS were considered simultaneously, the association of FGF-2 mRNA overexpression with recurrence and mortality was even more pronounced, whereas FGF-AS mRNA overexpression was associated with reduced risk for recurrence and improved survival. Conclusions: Overexpression of FGF-2 mRNA is associated with tumor recurrence and reduced survival after surgical resection of esophageal cancer and that these risks are reduced in tumors coexpressing the FGF-AS mRNA. These data support the hypothesis that FGF-AS is a novel tumor suppressor that modulates the effect of FGF-2 expression and may have potential clinical application to the development of novel therapeutic strategies.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Basic Fibroblast Growth Factor (FGF-2) Overexpression Is a Risk Factor for Esophageal Cancer Recurrence and Reduced Survival, which Is Ameliorated by Coexpression of the FGF-2 Antisense Gene

Barclay¹,

Li²,

Geldenhuys³

et al. 2005

Clinical Cancer Research

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Genomic landscape of developing male germ cells

Lee

Pang

Rennert

et al. 2009

Birth Defects Research Pt C

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Spermatogenesis is a highly orchestrated developmental process by which spermatogonia develop into mature spermatozoa. This process involves many testis-or male germ cell-specific gene products whose expressions are strictly regulated. In the past decade the advent of high-throughput gene expression analytical techniques has made functional genomic studies of this process, particularly in model animals such as mice and rats, feasible and practical. These studies have just begun to reveal the complexity of the genomic landscape of the developing male germ cells. Over 50% of the mouse and rat genome are expressed during testicular development. Among transcripts present in germ cells, 40% -60% are uncharacterized. A number of genes, and consequently their associated biological pathways, are differentially expressed at different stages of spermatogenesis. Developing male germ cells present a rich repertoire of genetic processes. Tissue-specific as well as spermatogenesis stagespecific alternative splicing of genes exemplifies the complexity of genome expression. In addition to this layer of control, discoveries of abundant presence of antisense transcripts, expressed psuedogenes, non-coding RNAs (ncRNA) including long ncRNAs, microRNAs (miRNAs) and Piwiinteracting RNAs (piRNAs), and retrogenes all point to the presence of multiple layers of expression and functional regulation in male germ cells. It is anticipated that application of systems biology approaches will further our understanding of the regulatory mechanism of spermatogenesis. †

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Challenging the dogma: the hidden layer of non‐protein‐coding RNAs in complex organisms

2003

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The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein-coding RNA (ncRNA) transcription in the higher eukaryotes and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of the structure of genetic regulatory systems in animals and plants may be incorrect. ncRNA dominates the genomic output of the higher organisms and has been shown to control chromosome architecture, mRNA turnover and the developmental timing of protein expression, and may also regulate transcription and alternative splicing. This paper re-examines the available evidence and suggests a new framework for considering and understanding the genomic programming of biological complexity, autopoietic development and phenotypic variation.

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Expression of alternatively spliced FGF-2 antisense RNA transcripts in the central nervous system: regulation of FGF-2 mRNA translation

Cited by 57 publications

References 41 publications

Basic Fibroblast Growth Factor (FGF-2) Overexpression Is a Risk Factor for Esophageal Cancer Recurrence and Reduced Survival, which Is Ameliorated by Coexpression of the FGF-2 Antisense Gene

Basic Fibroblast Growth Factor (FGF-2) Overexpression Is a Risk Factor for Esophageal Cancer Recurrence and Reduced Survival, which Is Ameliorated by Coexpression of the FGF-2 Antisense Gene

Genomic landscape of developing male germ cells

Challenging the dogma: the hidden layer of non‐protein‐coding RNAs in complex organisms

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