LncRNA lnc-RI regulates homologous recombination repair of DNA double-strand breaks by stabilizing RAD51 mRNA as a competitive endogenous RNA

Abstract

DNA double-strand break (DSB) repair is critical for the maintenance of genome stability. The current models of the mechanism of DSB repair are based on studies of DNA repair proteins. Long non-coding RNAs (lncRNAs) have recently emerged as new regulatory molecules, with diverse functions in biological processes. In the present study, we found that expression of the ionizing radiation-inducible lncRNA, lnc-RI, was correlate negatively with micronucleus frequencies in human peripheral blood lymphocytes. Knockdown of lnc-RI significantly increased spontaneous DSBs levels, which was confirmed to be associated with the decreased efficiency of homologous recombination (HR) repair of DSBs. The expression of RAD51, a key recombinase in the HR pathway, decreased sharply in lnc-RI-depressed cells. In a further investigation, we demonstrated that miR-193a-3p could bind with both lnc-RI and RAD51 mRNA and depressed the expression of lnc-RI and RAD51 mRNA. Lnc-RI acted as a competitive endogenous RNA (ceRNA) to stabilize RAD51 mRNA via competitive binding with miR-193a-3p and release of its inhibition of RAD51 expression. To our knowledge, this is the first study to demonstrate the role of lnc-RI in regulating HR repair of DSBs. The feedback loop established in the current study suggests that lnc-RI is critical for the maintenance of genomic stability.

Cancer-associated Fibroblast–promoted LncRNA DNM3OS Confers Radioresistance by Regulating DNA Damage Response in Esophageal Squamous Cell Carcinoma

“…LncRNAs were involved in many cellular biological processes including cell-cycle progression, apoptosis, and pluripotency of stem cells. Recent studies showed that lncRNAs were involved in DDR by sensing DNA damage, transducing damage signals, repairing damaged DNA, activating cell-cycle checkpoints, and inducing apoptosis (11). Our study aimed to investigate whether lncRNAs were involved in DNA damage repair following irradiation in ESCC and whether CAFs regulated the expressions of those functional lncRNAs in esophageal cancer cells.…”

DNA-methylation-mediated activating of lncRNA SNHG12 promotes temozolomide resistance in glioblastoma

“…However, the epigenetic regulation of lncRNAs and the subsequent effect on tumor progression, especially in terms of acquired chemoresistance, remain largely unknown. LncRNAs have been propounded to act as competitive endogenous RNA (ceRNA) that compete for microRNA (miRNA) binding, thereby playing a significant role in gene regulation [11,12]. The ceRNA network participates in the mediation of postoperative treatment resistance in some cancers but its role in TMZ resistance is rarely reported.…”

An LTR retrotransposon‐derived lnc RNA interacts with RNF 169 to promote homologous recombination

“…Previous studies have shown that the HR machinery is made up of various protein factors [4,10]. Although several lncRNAs may be involved in the regulation of the HR processes [28][29][30], few are characterized as HR components. In this study, we first identified a RNF169-interacting lncRNA PRLH1 that promoted HR repair.…”

“…Previous studies have shown that spontaneous and stress-induced HR is strictly inhibited by p53 through a direct interaction with some HR proteins [20,[24][25][26] or transcriptional repression of Rad51 [27]. Recent studies have shown that lncRNAs are emerging as regulators of HR repair [28][29][30], but whether they are involved in the p53-mediated repression of HR pathway remains unexplored.…”