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.

Long noncoding RNAs (lncRNAs) are important regulators of the biological functions and underlying molecular mechanisms of colorectal cancer (CRC). However, the role of the lncRNA ZEB1-AS1 in CRC is not thoroughly understood. In this study, we found that ZEB1-AS1 was markedly upregulated in CRC. ZEB1-AS1 knockdown significantly suppressed CRC cell proliferation and induced apoptosis, whereas enhanced expression of ZEB1-AS1 had the opposite effect. Bioinformatics analysis identified miR-181a-5p as a candidate target of ZEB1-AS1. Moreover, we found an inverse correlation between ZEB1-AS1 and miR-181a-5p expression in CRC tissue. Inhibition of miR-181a-5p significantly upregulated ZEB1-AS1, whereas overexpression of miR-181a-5p had the opposite effect, suggesting that ZEB1-AS1 is negatively regulated by miR-181a-5p. Using luciferase reporter and RIP assays, we found that miR-181a-5p directly targets ZEB1-AS1. Importantly, ZEB1-AS1 may act as an endogenous 'sponge' to regulate miRNA targets by competing for miR-181a-5p binding. In summary, our findings provide the evidence supporting the role of ZEB1-AS1 as an oncogene in CRC. Our study also demonstrates that miR-181a-5p targets not only protein-coding genes but also the lncRNA ZEB1-AS1.

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Increased levels of miRNA-30e downregulated activity of the Dll4/NICD/Hes1 signalling pathway by targeting the 3'-UTR of Dll4, which contributed to abnormal differentiation in small intestinal epithelia of DM mice.

BackgroundThe effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage.MethodsBALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively.ResultsCOX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05).ConclusionRebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.