Introduction of novel splice variants for CASC18 gene and its relation to the neural differentiation

Abstract

Background: CASC18 along with APPL2, OCC-1 and NUAK1 flanking genes are located in 12q23.3 locus which is known as a potential cancer predisposition locus. Only an uncharacterized EST was initially reported for CASC18 and it was crucial to find its full length sequence and function.

Methods and results: In an attempt to search for the CASC18's full-length gene sequence, other related ESTs were bioinformatically collected and four novel splice variants (designated as; CASC18-A, -B, -C and -D) were deduced and some were experimentally validated. Two transcription start sites and two alternative polyadenylation sites were deduced for CASC18 gene, using EST data mining and RACE method. CASC18-A and CASC18-D were exclusively expressed in neural cell lines and CASC18-D expression level was gradually increased during the NT2 differentiation to the neuron-like cells. Consistently, overexpression of CASC18-D variant in NT2 cells resulted in remarkable up-regulation of PAX6 neural differentiation marker, suggesting a crucial role of this variant in neural differentiation.

Conclusion: Here, we introduced seven novel transcription variants for human CASC18 gene in which CASC18-D has the potential of being used as a neural cell differentiation marker.

Keywords: CASC18 gene; Long non-coding RNA; NT2 differentiation, Oct4-A gene.