LncRNA RAD51-AS1/miR-29b/c-3p/NDRG2 crosstalk repressed proliferation, invasion and glycolysis of colorectal cancer.

LncRNAs are recently increasingly emerging as molecules that take its part in human carcinogenesis. A large body of literature has identified the functional roles of lncRNAs in the pathophysiology of CRC. The current study was intended to provide new ideas and perspectives for the functional role of lncRNA RAD51-AS1 in regulating CRC progression. Herein, a survey of RAD51-AS1 expression profile in The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) dataset revealed that RAD51-AS1 was downregulated in COAD specimens. Consistently, RAD51-AS1 expression was observed to be lower in CRC cell lines compared with normal cell line (NCM460). In the meanwhile, both the levels of miR-29b-3p and miR-29c-3p were prominently elevated in CRC cells. Functionally, administration of RAD51-AS1 refrained growth, invasion and migration of CRC cells. Additionally, accumulation of RAD51-AS1 hampered glucose consumption and lactate production, as well as the restraint of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) levels. More important, RAD51-AS1 functioned as a competing endogenous RNA (ceRNA) for sponging miR-29b-3p and miR-29c-3p, leading to enhancement of their common target N-myc downstream-regulated gene 2 (NDRG2). Mechanistically, the delivery of miR-29b/c-3p mimics or ablation of NDRG2 effectively blunted the salutary effects of RAD51-AS1 on CRC cell behaviors. Moreover, augmentation of RAD51-AS1 inhibited the tumorigenesis of CRC cells in vivo. Collectively, these findings provide comprehensive evidence that RAD51-AS1 repressed cell proliferation, migration, invasion and glycolysis process, ultimately contributing to the progression of CRC by repressing the miR-29b/c-3p/NDRG2 signaling axis, insinuating the putative potential of RAD51-AS1/miR-29b/c-3p/NDRG2 interaction network in unraveling CRC pathology and hopefully contributed to the treatment of CRC patients.