Genetic variations in UCA1, a lncRNA functioning as a miRNA sponge, determine endometriosis development and the potential associated infertility via regulating lipogenesis

Abstract

Endometriosis is a hormone-associated disease which has been considered as the precursor for certain types of ovarian cancer. In recent years, emerging evidence demonstrated potent roles of lncRNA in regulating cancer development. Since endometriosis shares several features with cancer, we investigated the possible involvement of cancer-related lncRNAs in endometriosis, including UCA1, GAS5 and PTENP1. By using massARRAY system, we investigated certain genetic variations in cancer-related lncRNAs that can change the thermo-stability, leading to up-regulation or down-regulation of those lncRNAs. Our data indicated three risk genetic haplotypes in UCA1 which can stabilize the RNA structure and increase the susceptibility of endometriosis. Of note, such alterations were found to be associated with long-term pain and infertility in patients. It has been known that UCA1 can function as a ceRNA to sponge and inhibit miRNAs, resulting in loss-of-control on downstream target genes. Gene network analyses revealed fatty acid metabolism and mitochondria beta-oxidation as the major pathways associated with altered UCA1 expression in endometriosis patients. Our study thus provides evidence to highlight functional/epigenetic roles of UCA1 in endometriosis development via regulating fatty acid metabolism in women.

Personalized Medicine in Cancer Pain Management

“…In their observational study, Crescioli et al found that the SNPs of IL6 (rs1800797) and TNF (rs1800629) may serve as possible indicators of baseline pain severity and opioid dosage requirements among pediatric cancer patients [ 40 ]. In a pioneer study, Chang et al investigated the putative participation of cancer-related lncRNAs in endometriosis and detected genetic variants in UCA1, a lncRNA serving as a miRNA sponge, which can be found in endometriosis development and is potentially associated with infertility via regulating lipogenesis [ 101 ]. Satkunananthan et al conducted a review to assess the polymorphism associations with variability in opioid therapy responses in Asian cancer pain patients.…”

Analysis of Long Non-Coding RNA (lncRNA) UCA1, MALAT1, TC0101441, and H19 Expression in Endometriosis

“…UCA1 can interact with various miRNAs, which then change gene expression profiles and control tumor progression. The participation of genetic variants of UCA1 in the development of endometriosis and related infertility is indicated [ 26 ].…”