Alternative Splicing of the Occ-1 Gene Generates Three Splice Variants and a Novel Exonic Microrna, Which Regulate the Wnt Signaling Pathway

Alternative Splicing of the Occ-1 Gene Generates Three Splice Variants and a Novel Exonic Microrna, Which Regulate the Wnt Signaling Pathway Publisher Pubmed

Najafi H¹ ; Soltani BM¹ ; Dokanehiifard S¹ ; Nasiri S² ; Mowla SJ¹

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1. Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-116, Iran
2. Tehran University of Medical Sciences, Shariati Hospital, Tehran, 1411713135, Iran

Source: RNA Published:2017

Abstract

The Wnt signaling pathway is hyperactivated in most colorectal cancers (CRC). Finding new regulators of this pathway represents the potential for cancer diagnosis or treatment. OCC-1 was initially reported as an up-regulated gene in colon carcinoma, without knowing its mechanism of action. Here, two novel transcript variants and an exonic microRNA that originated from the OCC-1 gene are reported, showing positive effects on Wnt activity. Up-regulation of the known OCC-1 variant (assigned as OCC-1A/B) was limited to CRC, and its overexpression increased survival of CRC-originated SW480 cells (Wnt+), while resulting in apoptosis of Wnt-suppressed SW480 cells or HeLa cells (Wnt-) detected by PI staining. Immunocytochemistry showed that the OCC-1A/Bencoded peptide was localized to the nucleus, where its overexpression resulted in Wnt signaling up-regulation, detected by TOP/ FOPflash assay. The noncoding portion of the OCC-1A/B transcript had a suppressive effect on Wnt activity and had a negative correlation with APPL2 neighboring gene expression. Unlike OCC-1A/B, the novel OCC-1C splice variant had no expression alteration in CRC, and it seemed to encode a smaller peptide with cytoplasmic localization. A 60-nucleotide (nt) fragment containing an AUG start codon is spliced out to produce an OCC-1D noncoding RNA variant. The 60-nt RNA was validated as the precursor of a novel microRNA, which we named miR-ex1. Both OCC-1D and miR-ex1 were coordinately up-regulated in CRC. MiR-ex1 functional analysis revealed that it is targeting the APC2 tumor suppressor gene and is an activator of the Wnt signaling pathway. Overall, the OCC-1 gene is now introduced as a novel Wnt signaling regulator and as a potential therapeutic target. © 2016 Najafi et al.

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Style	Citing Format
MLA	Najafi H, et al.. "Alternative Splicing of the Occ-1 Gene Generates Three Splice Variants and a Novel Exonic Microrna, Which Regulate the Wnt Signaling Pathway." RNA, vol. 23, no. 1, 2017, pp. 70-85.
APA	Najafi H, Soltani BM, Dokanehiifard S, Nasiri S, Mowla SJ (2017). Alternative Splicing of the Occ-1 Gene Generates Three Splice Variants and a Novel Exonic Microrna, Which Regulate the Wnt Signaling Pathway. RNA, 23(1), 70-85.
Chicago	Najafi H, Soltani BM, Dokanehiifard S, Nasiri S, Mowla SJ. "Alternative Splicing of the Occ-1 Gene Generates Three Splice Variants and a Novel Exonic Microrna, Which Regulate the Wnt Signaling Pathway." RNA 23, no. 1 (2017): 70-85.
Harvard	Najafi H et al. (2017) 'Alternative Splicing of the Occ-1 Gene Generates Three Splice Variants and a Novel Exonic Microrna, Which Regulate the Wnt Signaling Pathway', RNA, 23(1), pp. 70-85.
Vancouver	Najafi H, Soltani BM, Dokanehiifard S, Nasiri S, Mowla SJ. Alternative Splicing of the Occ-1 Gene Generates Three Splice Variants and a Novel Exonic Microrna, Which Regulate the Wnt Signaling Pathway. RNA. 2017;23(1):70-85.
BibTex	@article{ author = {Najafi H and Soltani BM and Dokanehiifard S and Nasiri S and Mowla SJ}, title = {Alternative Splicing of the Occ-1 Gene Generates Three Splice Variants and a Novel Exonic Microrna, Which Regulate the Wnt Signaling Pathway}, journal = {RNA}, volume = {23}, number = {1}, pages = {70-85}, year = {2017} }
RIS	TY - JOUR AU - Najafi H AU - Soltani BM AU - Dokanehiifard S AU - Nasiri S AU - Mowla SJ TI - Alternative Splicing of the Occ-1 Gene Generates Three Splice Variants and a Novel Exonic Microrna, Which Regulate the Wnt Signaling Pathway JO - RNA VL - 23 IS - 1 SP - 70 EP - 85 PY - 2017 ER -

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