Abstract
Long intergenic noncoding RNAs (lincRNAs) play important roles in regulating the biological functions and underlying molecular mechanisms of colorectal cancer (CRC). Here, we investigated the association of linc-POU3F3 and prognosis in CRC. We demonstrated that linc-POU3F3 was overexpressed in CRC tissues and positively correlated with tumor grade and N stage. Inhibition of linc-POU3F3 resulted in inhibition of cell proliferation and G1 cell cycle arrest, which was mediated by cyclin D1, CDK4, p18, Rb, and phosphorylated Rb. Inhibition of linc-POU3F3 induced apoptosis, and suppressed migration and invasion in LOVO and SW480 cell lines. This inhibition also increased the expressions of epithelial markers and decreased the expressions of mesenchymal markers, thus inhibiting the cancer epithelial-mesenchymal transition. The decreased migration and invasion following linc-POU3F3 knockdown were mediated by an increased BMP signal. Furthermore, autophagy was enhanced by linc-POU3F3 knockdown, suggesting the involvement of autophagy in the induced apoptosis. Collectively, linc-POU3F3 might be crucial in pro-proliferation, anti-apoptosis, and metastasis in LOVO and SW480 cells by regulating the cell cycle, intrinsic apoptosis, BMP signaling and autophagy. Thus, linc-POU3F3 is a potential therapeutic target and novel molecular biomarker for CRC.
Highlights
Colorectal cancer (CRC) is the fourth leading cause of cancer related death in the world, and the third most frequent cause of cancer-related death in western societies [1, 2]
Information from UCSC Browser showed that linc-POU3F3 is a transcript of 2,874 bp expressed from human chromosome 2 q12.1, comprising four exons on the reverse strand, and lying upstream from the POU3F3 gene, which is a member of the class III POU family of transcription factors (Fig. 1A)
The expression level of linc-POU3F3 was assessed in 45 paired CRC samples and histologically normal adjacent tissues using quantitative real-time PCR, with normalization to GAPDH
Summary
Colorectal cancer (CRC) is the fourth leading cause of cancer related death in the world, and the third most frequent cause of cancer-related death in western societies [1, 2]. The incidence and mortality of CRC in some developing countries, such as China, have continued to increase along with their transition towards the so-called western lifestyle, such as the consumption of high-fat diets and physical inactivity. Long noncoding RNAs (lncRNAs) generally comprise ribonucleic acid molecules longer than 200 nucleotides without defined open reading frames, which regulate gene expression at epigenetic transcriptional and post-transcriptional levels [6]. Long intervening noncoding RNAs (lincRNAs), a subtype of lncRNAs, are transcript units located within genomic intervals between two protein coding genes [7, 8]. There are thousands of functional lincRNAs yet to be identified
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