miR-21 Targets 15-PGDH and Promotes Cholangiocarcinoma Growth

Abstract

MicroRNAs (miRs) are a group of small, non-coding RNAs that modulate the translation of genes by binding to specific target sites in the target mRNA. This study investigated the biological function and molecular mechanism of microRNA-21 (miR-21) in human cholangiocarcinoma. In situ hybridization analysis of human cholangiocarcinoma specimens showed increased miR-21 in cholangiocarcinoma tissue compared to the non-cancerous biliary epithelium. Lentiviral transduction of miR-21 enhanced human cholangiocarcinoma cell growth and clonogenic efficiency in vitro, whereas inhibition of miR-21 decreased these parameters. Over-expression of miR-21 also promoted cholangiocarcinoma growth using an in vivo xenograft model system. The NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH/HPGD), a key enzyme that converts the protumorigenic prostaglandin E2 (PGE2) to its biologically inactive metabolite, was identified as a direct target of miR-21 in cholangiocarcinoma cells. In parallel, cyclooxygenase-2 (COX2) over-expression and PGE2 treatment increased miR-21 levels and enhanced miR-21 promoter activity in human cholangiocarcinoma cells.

Exosomes in liver pathology

“…A study using human CCA specimens has revealed elevated miR-21 expression in the CCA tissue compared with noncancerous biliary epithelium. This study has also demonstrated that overexpression of miR-21 promotes CCA growth by targeting the key enzyme for prostaglandin conversion, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) [39]. These studies support the notion that miR-21 may be another strong candidate biomarker in liver pathology.…”

MicroRNA MIR21 (miR-21) and PTGS2 Expression in Colorectal Cancer and Patient Survival

“…In addition, studies of human colorectal cancer tissue have shown that MIR21 is upregulated in colorectal cancer cells, and that tumor MIR21 expression level is associated with high-level expression of the genes involved in inflammatory responses and worse clinical outcome (15, 16). MIR21 appears to downregulate gene products that catalyze degradation of PGE 2 , which leads to increased level of PGE 2 in the tumor microenvironment and promotes tumor growth in a xenograft model (17). Hence, there might be a synergistic effect of MIR21 and PTGS2 on tumor progression.…”

Elevation of miR-21, through targeting MKK3, may be involved in ischemia pretreatment protection from ischemia–reperfusion induced kidney injury

“…miR-21 is highly up-regulated in hypoxia and plays an important role in cell growth and proliferation [13]. miR-21 is involved in various pathological and physical processes, inhibiting inflammation and apoptosis via down-regulation of target genes [14][15][16][17][18]. miR-21 plays a number of roles in solid cancers [19].…”