The long noncoding RNAs (lncRNAs) Colon Cancer-Associated Transcripts 1 and 2 (CCAT1 and CCAT2) are located in a recurrently amplified region in cancers.
Among long non-coding RNAs (lncRNAs) located in the chromosome 8q24 loci and involved in the carcinogenesis are colon cancer associated transcript 2 (<i>CCAT2</i>) and cancer susceptibility candidate 8 (<i>CASC8</i>).
CCAT2 expression in cancer tissue was significantly higher than in noncancer tissue (p < 0.001), particularly in cases of metastatic cancer (p < 0.001).
29-17.96, <i>p</i><0.001) in a random-effects model (I<sup>2</sup>=41.9%, <i>p</i>=0.16).Likewise,we also found that high CCAT2 expression could predict unfavourable overall survival with pooled hazard ratio (HR) of 2.23 (95 % CI 1.68-2.96, <i>p</i><0.00001) by a random-effects model (I<sup>2</sup>=37.5%, <i>p</i>=0.143) and poor metastasis-free survival in cancer patients (HR= 2.08, 95%CI:1.37-3.18 <i>p</i>=0.001) by a fixed-effects model (I<sup>2</sup>=0.0%, <i>p</i>=0.807).
Here, we show that the long ncRNA CCAT2, located at the 8q24 amplicon on cancer risk-associated rs6983267 SNP, regulates cancer metabolism in vitro and in vivo in an allele-specific manner by binding the Cleavage Factor I (CFIm) complex with distinct affinities for the two subunits (CFIm25 and CFIm68).
Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk.