Abstract
LncRNAs have been proven closely correlated to tumor progression. A recent study identified LncRNA TPT1-AS1 (TPT1-AS1) as one of the liver-metastasis associated LncRNAs in colorectal cancer (CRC). In this study, we report that TPT1-AS1 is upregulated in CRC tissues, which is associated with poor prognosis. Functional assays unravel a pro-angiogenesis and metastasis role of TPT1-AS1. Mechanistically, Flexmap 3D assays reveal that TPT1-AS1 upregulates the VEGFA secretion in CRC cells. RNA immunoprecipitation and mRNA stability assays further show that TPT1-AS1 interacts with nuclear factor 90 (NF90) and subsequently promotes the association between NF90 and VEGFA mRNA, which leads to the upregulation of VEGFA mRNA stability. Therefore, we elucidate a new regulatory mechanism of TPT1-AS1 in CRC angiogenesis and targeting the TPT1-AS1/NF90/VEGFA axis may provide a useful strategy for diagnosis and treatment for colorectal cancer patients.
Highlights
Colorectal cancer (CRC) is the second most common cause of cancer worldwide and lack of detection for early metastasis [1]
The results indicated that higher levels of TPT1-AS1 expression were significantly correlated to worse overall survival (OS) and disease-free survival (DFS) (Figure 1E and 1F)
The results revealed that TPT1-AS1 interacted with nuclear factor 90 (NF90) protein and upregulated the stability of vascular endothelial growth factor A (VEGFA) mRNA
Summary
Colorectal cancer (CRC) is the second most common cause of cancer worldwide and lack of detection for early metastasis [1]. It has been revealed that not more than 2% of the human genome are protein coding genes, while the majority of transcripts are non-protein coding RNAs [4] These transcripts are processed into microRNAs, pseudogenes, or long non-coding RNAs. Increasing evidences indicate that lncRNAs play crucial roles in many cancer cellular processes, such as proliferation, immune response, metastasis, angiogenesis [5, 6]. A study analyzed the RNA sequencing and microarray data from TCGA database to find differentially expressed lncRNAs in CRC. They identified the liver metastasis-associated lncRNAs, www.aging-us.com among which Lnc-TPT1-AS1 was significantly upregulated in CRC liver metastasis samples [7]. No researchers have detected the function or regulatory mechanism of TPT1-AS1 in colorectal cancer
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