Genetic impacts on thermostability of onco-lncRNA HOTAIR during the development and progression of endometriosis

Abstract

HOTAIR is a well-known long non-coding RNA (lncRNA) involved in various cellular signaling, whereas its functional impacts on endometriosis development are still largely unknown. To this end, six potential functional single nucleotide polymorphisms (SNPs) in HOTAIR, with minor allele frequencies more than 10% in Han population and altered net energy of RNA structures larger than 0.5 kcal/mol, were selected for genotyping study. The study included 207 endometriosis patients and 200 healthy women. Genetic substitutions at rs1838169 and rs17720428 were frequently found in endometriosis patients, and rs1838169 showed statistical significance (p = 0.0174). The G-G (rs1838169-rs17720428) haplotype showed the most significant association with endometriosis (p < 0.0001) with enhanced HOTAIR stability, and patients who harbor such haplotype tended to show higher CA125. Data mining further revealed higher mRNA HOTAIR levels in the endometria of patients with severe endometriosis which consistently showed reduced HOXD10 and HOXA5 levels. HOTAIR knockdown with specific shRNAs down-regulated cell proliferation and migration with the induction of HOXD10 and HOXA5 expression in human ovarian clear cancer cells. Our study therefore provided evidence to indicate a prominent role of HOTAIR in promoting endometriosis, which could be used as a potential target for clinical applications.

Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature)

“…Research indicates a significant role for HOTAIR in promoting endometriosis [ 175 ]. HOTAIR can be used as a potential target for clinical applications.…”

Ovarian cancer: epigenetics, drug resistance, and progression

“…HOX antisense intergenic RNA ( HOTAIR ) was significantly increased in 44 OC tissues compared with 14 normal ovary tissues [ 68 ]. HOTAIR levels were positively correlated with the FIGO stage, histological grade of the tumor, lymph node metastasis and reduced OS and DFS [ 69 ].…”

The Role of Long Non-Coding RNAs in Endometriosis

“…This indicates another possible mechanism for lncRNA regulation, whereby dysregulation of CDC42 due to the risk of an SNP affecting enhancer competition with the LINC00339 promoter leads to predisposition to endometriosis. Recently, genetic variations at the rs1838169 and rs17720428 SNPs sites on chromosome 12q13.3 in HOTAIR have been shown to be frequently detected in patients with endometriosis [ 30 ]. These variants appear to increase the stability of the lncRNA, resulting in reduced levels of HOXD10 and HOXA5 transcripts regulated by HOTAIR .…”