Recently, thousands of long noncoding RNAs (lncRNAs) have been found to be aberrantly expressed in various types of cancers. Since colorectal cancer (CRC) is the third most common human malignancy worldwide, we investigated lncRNAs misregulated in this type of cancer, and identified SNHG15 as a potentially oncogenic lncRNA. By analyzing expression data from CRC patients available on TCGA, we observed that SNHG15 upregulation is an early event in colorectal cancer promotion and its expression is maintained at high levels until later stages. As SNHG15 sequence has two E-box binding motifs for MYC, we analyzed colorectal adenocarcinoma RNA-seq data from TCGA and revealed SNHG15 is upregulated in the samples with high levels of MYC expression. After silencing MYC in a CRC cell line, the level of SNHG15 was decreased significantly. So SNHG15 transcription could be regulated by MYC. Using CRISPR-Cas9 system, we deleted the region containing exons 3 to 5 from SNHG15 and several clones were obtained with decreased expression of SNHG15. Results showed that these clones have low proliferation and colony formation capacity. However, we did not observe any significant changes in cell cycle and percentage of apoptotic cells. To investigate the effects of SNHG15 in vivo, we injected clones to immunodeficient mice and found that the tumors formed by knocked-out cells were obviously smaller and lighter than wild type cells. In summary, these results describe for the first time an important role of SNHG15 in promoting colon cancer and suggest a novel prognostic marker and target for RNA-based therapies.

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