Different Basic Fibroblast Growth Factor and Fibroblast Growth Factor-Antisense Expression in Eutopic Endometrial Stromal Cells Derived from Women with and without Endometriosis

Abstract

In all species studied, the basic fibroblast growth factor (bFGF) gene is transcribed into multiple mRNAs, one of which is an antisense RNA (1B FGF-AS) probably involved in regulating the stability of the sense transcript. In this study we investigated whether the regulatory mechanisms of bFGF expression might be altered in endometrial stromal cells derived from women with endometriosis. bFGF and 1B FGF-AS mRNA levels were quantified in primary cultures of eutopic endometrial stromal cells derived from 29 women without endometriosis and 24 patients affected by the disease. When the data were analyzed according to the phase of the menstrual cycle, endometrial stromal cells derived from patients in the late proliferative phase showed significantly higher bFGF mRNA values and significantly lower 1B FGF-AS mRNA levels compared with control samples. Furthermore, the mean bFGF/1B FGF-AS mRNA ratio was significantly higher in endometrial stromal cells derived from patients compared with that in controls (mean +/- SEM, 2.31 +/- 0,55 and 0.77 +/- 0.14, respectively; P = 0.009). Moreover, for bFGF expression the differences existing at the mRNA level were maintained at the protein level. These findings support the hypothesis that 1B FGF-AS mRNA could regulate the expression of the sense transcript and suggest that in endometrial cells derived from patients, the presence of higher bFGF levels could improve their ability to proliferate at the ectopic site.

Extensive relationship between antisense transcription and alternative splicing in the human genome

“…We refer to this phenomenon as antisensecorrelated splicing. Although a few examples of antisense-correlated splicing events have been reported in the literature (Hastings et al 1997;Mihalich et al 2003;Yan et al 2005;Annilo et al 2009), we provide for the first time evidence linking antisense transcription to alternative splicing across the majority of SAS loci expressed in human lymphoblastoid cell lines.…”

“…In a limited number of cases, antisense transcription has been correlated to sense gene splicing (Mihalich et al 2003;Louro et al 2007;Annilo et al 2009) or shown to regulate sense gene splicing (Krystal et al 1990;Kuersten and Goodwin 2003;Yan et al 2005;Beltran et al 2008;Allo et al 2009). One well-characterized example is antisense-mediated splicing regulation of the thyroid hormone receptor THRA by the antisense transcript NR1D1 (Hastings et al 1997).…”

Natural Antisense Transcripts

“…The sense-encoded protein induces growth, differentiation and antiapoptotic behavior; over expression of FGF-2 is linked to tumor progression and ectopic cell proliferation. 30 The FGF-related antisense transcript was first identified in Xenopus oocytes. Interestingly, Kimelman and Kirschner found that the sense and the antisense transcript were edited in the overlapping region suggesting that the two transcripts hybridized.…”

“…Interestingly, Kimelman and Kirschner found that the sense and the antisense transcript were edited in the overlapping region suggesting that the two transcripts hybridized. [30][31][32] Subsequently the antisense transcript was cloned from various species including chick, rat and human. 16,33,34 Sense and antisense transcripts overlap tail to tail in the 3' non-coding region, only the Xenopus antisense transcript reaches into the open reading frame of the sense transcript.…”

“…Generally, reduced levels of the GFG-RNA favor FGF-induced carcinogenic progression, 29 or, in the case of endometriosis ectopic implantation of endometric tissue. 30 HIF-1α. The hypoxia inducible factor (HIF-1) is a heterodimeric transcription factor that coordinates gene expression in response to oxygen restriction.…”