Long Noncoding RNA TCONS_00016406 Attenuates Lipopolysaccharide-Induced Acute Kidney Injury by Regulating the miR-687/PTEN Pathway

Abstract

Acute kidney injury (AKI) is a common and serious complication of sepsis accompanied by kidney dysfunction resulting from various etiologies and pathophysiological processes. Unfortunately, there is currently no ideal therapeutic strategy for AKI. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) play important regulatory roles in the pathogenesis of sepsis-associated AKI. In this study, lncRNA TCONS_00016406 (termed lncRNA 6406), a novel lncRNA identified by using TargetScan, was significantly downregulated in the kidney tissues of mice with sepsis-associated AKI. This study aimed to explore the role of lncRNA 6406 in lipopolysaccharide (LPS)-induced AKI and its potential molecular mechanism. The models of sepsis-induced AKI (called LPS-induced AKI models) in mice and cell lines were established with male C57BL/6 mice and renal tubular epithelial (PTEC) cells, respectively. Twenty-four hours after LPS administration, kidneys and cell samples were collected after various treatments to examine the alterations in the lncRNA 6406 levels and to evaluate the effects on LPS-induced inflammation, oxidative stress, and apoptosis through real-time PCR (RT-PCR) analysis, western blotting, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The results revealed that lncRNA 6406 could significantly attenuate LPS-induced AKI, as shown by the alleviation of inflammation, the suppression of oxidative stress and the inhibition of apoptosis. Mechanistically, a luciferase reporter assay and additional research showed that lncRNA 6406 functioned as a ceRNA to sponge miRNA-687, thereby modulating LPS-stimulated AKI by targeting the miR-687/PTEN axis; thus, this study presents a novel therapeutic strategy or sepsis-associated AKI.

LncRNA KCNQ1OT1 (potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1) aggravates acute kidney injury by activating p38/NF-κB pathway via miR-212-3p/MAPK1 (mitogen-activated protein kinase 1) axis in sepsis

“…LncRNAs can serve as a competing endogenous RNA (ceRNA) to indirectly regulate downstream messenger RNAs by interacting with miRNAs, thus influencing disease phenotypes in kidneys [ 49 ]. For example, lncRNA TCONS_00016406 interacts with miR-687 to regulate the expression of phosphatase and tensin homolog (PTEN), thereby attenuating LPS-stimulated AKI, as shown by alleviation of inflammation, the inhibition of oxidative stress and the suppression of cell apoptosis [ 50 ]. LncRNA SNHG14 promotes the production of inflammatory cytokines in LPS-induced HK-2 cells by interacting with miR-495-3p to regulate downstream homeodomain interacting protein kinase 1 (HIPK1)/NF-κB/p65 signaling pathway [ 51 ].…”

Knockdown of lncRNA ANRIL suppresses the production of inflammatory cytokines and mucin 5AC in nasal epithelial cells via the miR-15a-5p/JAK2 axis

“…Long non-coding RNAs (lncRNAs) are transcripts of ~200-10,0000 nucleotides in length that are not translated into proteins (8,9). lncRNAs have been confirmed to serve important biological roles in numerous biological processes, including DNA damage, programmed cell death and inflammation (10)(11)(12). Furthermore, lncRNAs have also been reported to participate in the pathogenesis of AR (13)(14)(15).…”

Non-Coding RNAs in Kidney Diseases: The Long and Short of Them

“…In this study, the lncRNA TCONS_00021712 was the most upregulated and TCONS_00016406 (lncRNA 6406) the most downregulated [ 13 ]. In line with these data, reduced renal lncRNA 6406 expression was observed in an experimental model of SI-AKI induced by administration of lipopolysaccharide (LPS) [ 14 ]. LncRNA 6406 decreased LPS-mediated inflammation, oxidative stress and cell death via regulation of miR-687/PTEN axis [ 14 ].…”

“…In line with these data, reduced renal lncRNA 6406 expression was observed in an experimental model of SI-AKI induced by administration of lipopolysaccharide (LPS) [ 14 ]. LncRNA 6406 decreased LPS-mediated inflammation, oxidative stress and cell death via regulation of miR-687/PTEN axis [ 14 ]. Furthermore, the lncRNA TCONS_00016233 plasma concentration was mainly elevated in sepsis-associated AKI patients, serving as an early diagnosis biomarker for this subtype of AKI [ 15 ].…”