ZFAS1 promotes rRNA 2’O-methylationin by recruiting NOP58 contributes to colorectal cancer progression

Increasing evidence suggested that small nucleolar RNAs (snoRNAs) and long non-coding RNAs (LncRNAs) were master regulators of gene regulation at epigenetic modification level, however, the underlying mechanism in colorectal cancer (CRC) have not been investigated. To demonstrate the involvement of LncRNA and snoRNAs in 2’-O-methylation (Me) in tumorigenesis, we develop the LncRNAs-snoRNAs microarray of paired CRC tissues, and found an unrecognized ZFAS1-NOP58- SNORD12C/78 signaling axis in CRC tumorigenesis through recognizing the consensus AAGA motif of ZFAS1 which directly binds to NOP58 protein, and accelerating the snoRNPs assemble for further guiding 2’-O-Me of 28S rRNA. Strikingly, overexpression SNORD12C/78 induces 2’-O-Me modification upon ZFAS1, and affects RNA stability and translation activity of their downstream targets (e.g., EIF4A3,LMAC2, etc.), thereby promoted CRC cell proliferation, invasion and inhibited apoptosis in vitro and in vivo. Thus, these results sheds new light on our understanding of lncRNAs-snoRNPs mediated rRNA 2'-O-methylations in CRC tumorigenesis. RNA expression profiles of 4 colorectal cancer tissues and 4 paracancer tissues