Ellagic acid inhibits human colon cancer HCT-116 cells by regulating long noncoding RNAs

Abstract

The natural phenolic compound ellagic acid exerts anti-cancer effects, including activity against colorectal cancer (CRC). Previously, we reported that ellagic acid can inhibit the proliferation of CRC, and can induce cell cycle arrest and apoptosis. This study investigated ellagic acid-mediated anticancer effects using the human colon cancer HCT-116 cell line. After 72 h of ellagic acid treatment, a total of 206 long noncoding RNAs (lncRNAs) with differential expression greater than 1.5-fold were identified (115 down-regulated and 91 up-regulated). Furthermore, the co-expression network analysis of differentially expressed lncRNA and mRNA showed that differential expressed lncRNA might be the target of ellagic acid activity in inhibiting CRC.

Fig. 1

Profiling of ellagic acid-regulated lncRNA and coding RNA. The red dots to the left and to the right of the vertical green lines indicate more than a 1.5-fold change. Statistical significance was defined as fold change ≥1.5 and P value ≤ 0.05 between ellagic acid-treated and control (DMSO) groups. DMSO, dimethyl sulfoxide; lncRNA, long noncoding RNA.

Fig. 2

LncRNA from DMSO- and ellagic acid-treated HCT116 cells. (a) Heat map presentation of the expression profile of lncRNA. Each column represents a sample and each row represents a gene. Three independent experiments for each DMSO and ellagic acid-treatment group. (b) The category and distribution of the differentially expressed lncRNA in DMSO- and ellagic acid-treated HCT116 cells. DMSO, dimethyl sulfoxide; lncRNA, long noncoding RNA.

Fig. 3

Gene Ontology analysis of lncRNA-associated with coding genes. (a) Gene Ontology analysis of coding genes in which one coding gene is associated with at least three lncRNA. The top 10 significantly enriched molecular functions along with their scores are listed on the x-axis and the y-axis, respectively. (b) KEGG pathway analysis of coding genes in which one lncRNA is connected to at least three mRNAs. The size of the dots indicates the number of enriched PCGs; the color of the dots represents the degree of significance based on the P value. KEGG, Kyoto Encyclopedia of Genes and Genomes; lncRNA, long noncoding RNA; PCGs; protein-coding genes.

Fig. 4

Co-expression network of DE lncRNA and differentially expressed mRNA. The squares represent lncRNA, the circles represent mRNA, the size of the shape represents the weighted value, red indicates up-regulation, and blue indicates down-regulation. lncRNA, long noncoding RNA.