LINC00852 inhibits colorectal cancer progression by regulating cell apoptosis, epithelial‒mesenchymal transition, invasion, and cuproptosis through miR-1276/LACTB.

Abstract

Exploring the role of key genes in colorectal cancer (CRC) progression to identify effective targets is highly practical. Previous studies have shown that miR-1276/ACTB plays an important regulatory role in CRC. In addition to miRNA, lncRNA also play a crucial role in tumour progression. However, there are currently no studies exploring the relationship between lncRNAs and miR-1276/LACTB. Analysis of the relationship between lncRNAs and miR-1276 using ENCORI database showed that lncRNA-LINC00852 bound to miR-1276 and inhibited its expression, thereby promoting LACTB expression, and miR-1276 upregulation weakened the ability of LINC00852 to promote LACTB expression. ENCORI and TCGA data also indicated that the expression of LINC00852 and LACTB in CRC was significantly downregulated, while miR-1276 expression was significantly upregulated. LINC00852 overexpression promoted E-cadherin expression, increased the activities of Caspase-3/8/9 and PARP, inhibited the expression of N-cadherin and Vimentin, and decreased the expression and secretion of MMP-2 and MMP-9. LINC00852 inhibited CRC cell viability, invasion and migration while promoting apoptosis. miR-1276 overexpression or LACTB knockdown significantly blocked the regulatory effect of LINC00852 on CRC cell biological function. Further xenograft mouse model confirmed that LINC00852 downregulated miR-1276 expression, enhanced the expression of LACTB and FDX1, increased tumour copper levels and inhibited tumour formation, indicating that the anticancer effect of LINC00852/LACTB may also be related to cuproptosis. However, LACTB knockdown blocked the inhibitory effect of LINC00852 on tumour formation. Therefore, LINC00852 inhibits CRC progression through miR-1276/LACTB, indicating that LINC00852/miR-1276/LACTB axis is an important pathway closely related to the occurrence and development of CRC.