Figure 4.

Functional consequences of SNPs affecting lncRNAs. Different SNPs in the ANRIL lncRNA gene promoter promote and repress ANRIL expression, respectively. ANRIL associates with polycomb repressor complexes (PRCs) to silence CDKN2B expression. ANRIL may also bind the YY1 transcription factor to promote IL6 expression. Finally, a circular form of ANRIL was reported to promote proliferation. ANRIL promoter SNPs may impact on these cancer- and inflammation-relevant functions of ANRIL lncRNA. CCAT2 lncRNA is transcribed from chromosome 8 and may bind to the MYC locus on the same chromosome, thereby promoting MYC expression. Alternatively, CCAT2 may bind TCFL2 to promote WNT and thereby MYC expression. A SNP was shown to elevate CCAT1 expression. The SNP also promotes binding of CCAT2 to CFIm25, thereby promoting alternative splicing of GLS mRNA and thus cancer cell proliferation. LncRNA PCAT1 is under negative control by the PRC2 complex. A prostate cancer-associated SNP in the PCAT1 promoter confers increased binding of the dihydrotestosterone (DHT) associated androgen receptor (AR), in complex with the one-cut transcription factor, which leads to increased PCAT1 levels. In complex with AR and LSD1, PCAT1 promotes expression of cancer associated genes.