Abstract
As a transcription coactivator, Yes‐associated protein 1 (YAP1)'s role in tumorigenesis is well established. However, the mechanism of YAP1‐regulating long noncoding RNAs (lncRNA) in tumors is still largely unknown. Here, a YAP1 target gene, long intergenic noncoding RNA 00152 (LINC00152), which is highly expressed in colorectal cancer (CRC), is identified. The oncogenic functions of LINC00152 in CRC are demonstrated by a panel of in vitro and in vivo experiments. Further studies reveal the potential downstream mechanisms of LINC00152, which can act as a competing endogenous RNA sponging with miR‐632 and miR‐185‐3p to regulate Fascin actin‐bundling protein 1 (FSCN1) expression and thus promote the malignant proliferation and metastasis in CRC cells. Targeting the YAP1/LINC00152/FSCN1 axis inhibits the progression of CRC. This finding provides a new regulatory model of the “YAP1‐lncRNA” in CRC, which gives rise to a new perspective, “YAP1/LINC00152/miR‐632‐miR‐185‐3p/FSCN1,” to explore the cancer‐promoting mechanism of YAP1 involved in CRC.
Highlights
Yes-associated protein 1 (YAP1) and LINC00152 were highly expressed in 83 cases colorectal cancer (CRC) tissues compared with matched para-tumor tissues, LINC00152 expression was positively correlated with YAP1 level (Figure 1C)
YAP1 acts as a transcriptional coactivator interacting with the corresponding transcription factors to activate downstream mRNA and long noncoding RNAs (lncRNA) expression
YAP1 interacts with TEAD1 bound to the lncRNA BCAR4 promoter, forming the YAP1-BCAR4 axis which plays an oncogenic role in breast cancer development.[13]
Summary
To investigate the “YAP1-lncRNAs” regulatory axis in CRC, we constructed a screening strategy (Figure 1A) via combination of two sets of gene expression profile date: one is to analyze the differentially expressed lncRNAs induced by si-YAP1 in CRC cells (i.e., si-YAP1 vs si-NC in colon cancer cells, to explore the downstream molecules of YAP1, see our previous study,[16] #GSE92335) through significant analysis of microarray (SAM);[17] the another is to analyze the differentially expressed lncRNAs between colorectal cancer biopsies and normal colorectal tissues using two sets of microarray data (#GSE41328 and GSE9348) (Figure 1B). YAP1 and LINC00152 were highly expressed in 83 cases CRC tissues compared with matched para-tumor tissues, LINC00152 expression was positively correlated with YAP1 level (Figure 1C). The expression of LINC00152 was positively correlated with YAP1 and its target gene CTGF[18] in CRC samples (Figure S1B,D,E, Supporting Information). These results demonstrated that LINC00152 is a downstream lncRNA of YAP1, and is highly expressed in human CRC tissues, predicting unfavorable prognosis
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