Gaplinc Promotes Invasion In Colorectal Cancer By Targeting SNAI2 Through Binding With PSF And NONO

Colorectal cancer(CRC)is one of the most common malignant tumor in the world with 1.3 million increasing new cases each year worldwide.Tumor metastasis is the main cause of treatment failure in patients with CRC.It is reported that long noncoding RNAs(1ncRNAs)is involved in tumor metastasis,but its function and mechanism in the process of CRC metastasis is not clear.The objective of this study is to explore the key metastasis-associated IncRNA of CRC,as well as its effects and related mechanism in CRC metastasis.We used IncRNA microarray technology to screen a total of 1133 dysregulated IncRNA transcripts in metastatic lymph node,compared with normal lymph node.Bioinformatics analysis showed that GAPLINC(gastric adenocarcinoma predictive long intergenic noncoding)might be related to tumor-associated pathways and was identified to further study.The increased expression of GAPLINC was found to be positively correlated with larger tumor size,tumor stage(T stage),lymphatic metastasis(N stage),and shorter survival of patients with CRC by assessing the expression level of GAPLINC in 180 pairs of CRC tissues and matched normal tissues using in situ hybridization analysis.Besides,the decreased expression of GAPLINC could signifcantly repress CRC cell invasion in vitro and also inhibit proliferation in vitro and in vivo.RNA pull-down with mass spectrum experiments revealed that PSF(PTB-associated splicing factor)and NONO(non-POU-domain-containing octamerbinding)protein bound to GAPLINC and reversed the effect of GAPLINC on cell invasion.However,the mRNA and protein levels of PSF and NONO did not change when interfering with the expression of GAPLINC.Gene array and western blot identifed that SNAI2(snail family zinc fnger 2)was involved in the biological processes of GAPLINC/PSF/NONO.Our results showed that GAPLINC was a potential prognostic factor for patients with CRC and regulated the biological functions of CRC cells.GAPLINC was also found to combine with PSF and NONO to promote the influence of GAPLINC on cell invasion partly via increasing the expression of SNAI2.