Long Noncoding RNA Antisense Noncoding RNA in the INK4 Locus Correlates With Risk, Severity, Inflammation and Infliximab Efficacy in Crohn's Disease

Background: The aim of this study was to investigate the association of intestinal mucosa long noncoding RNA (IncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) expression with disease risk, activity and inflammatory cytokines levels of Crohn's disease (CD). Methods: Forty-two patients with active CD (A-CD), 59 patients with CD in remission (R-CD) and 67 controls were consecutively recruited. Intestinal mucosa samples were collected from all participants at baseline and from A-CD patients at 3-months after infliximab treatment. LncRNA ANRIL level, mRNA expression of tumor necrosis factor-alpha, interleukin (IL)-10, IL-17, IL-23 and interferon gamma were assessed by quantitative polymerase chain reaction. C-reactive protein, erythrocyte sedimentation rate and Crohn's disease activity index were used to evaluate the disease activity of CD. Results: LncRNA ANRIL expression was decreased in patients with A-CD compared with patients with R-CD (P < 0.001) and controls (P < 0.001) and was also reduced in patients with R-CD compared with controls (P < 0.001). Receiver operating characteristic curves showed that IncRNA ANRIL expression distinguished CD, A-CD and R-CD from controls, as well as A-CD from R-CD. Additionally, IncRNA ANRIL expression was negatively associated with Crohn's disease activity index (P = 0.002), C-reactive protein (P < 0.001) and erythrocyte sedimentation rate (P = 0.001), and associated with tumor necrosis factor-alpha (P < 0.001), IL-17 (P < 0.001) and interferon gamma messenger RNA levels (P = 0.004) but positively associated with IL-10 messenger RNA level (P = 0.002). Furthermore, IncRNA ANRIL expression was increased after infliximab treatment compared with baseline in patients with A-CD that responded to treatment (P < 0.001) but remained stable in patients with A-CD that did not respond (P = 0.897). Conclusions: IncRNA ANRIL downregulation in intestinal mucosa correlates with increased disease risk, higher disease activity and elevated proinflammatory cytokines levels, and its change associates with infliximab treatment response in patients with CD.