Circ_0114427 promotes LPS-induced septic acute kidney injury by modulating miR-495-3p/TRAF6 through the NF-κB pathway

Circular RNAs in Acute Kidney Injury: Roles in Pathophysiology and Implications for Clinical Management

“…Separate studies showed that circ-FANCA (hsa_circ_0040994), circ-BNIP3L (hsa_circ_0002131), circ-HIPK3, hsa_circ_0114427, and hsa_circ_0114428 were each increased in the sera of patients with septic AKI [ 31 , 32 , 34 , 35 , 36 ]. In human cell line models of septic AKI, HK-2 cells treated with LPS showed elevated cytoplasmic expression of circ-FANCA, circ-BNIP3L, hsa_circ_0114427, hsa_circ_0114428, circ-HIPK3, and circ-TLK1, whereas knockout of circ-FANCA, circ-BNIP3L, hsa_circ_0114427, hsa_circ_0114428, circ-HIPK3, and circ-TLK1, respectively, resulted in the attenuation of LPS-induced cell injury, implying a direct pathogenic role of these circRNAs [ 31 , 32 , 34 , 35 , 36 , 37 ]. These effects seem to be mediated via interaction with other epigenetic regulators.…”

“…Decreased expression of miR-370-3p in septic AKI was associated with elevated expression of MYD88, which is a downstream adaptor molecule of the TLR and IL-1 receptor families and modulates the activity of mitogen-activated protein kinase (MAPK) and NF-κB pathways [ 32 ]. Direct interaction was observed between both hsa_circ_0114427 and hsa_circ_0114428 with miR-495-3p, which regulates TRAF6 expression via the NF-κB signalling pathway [ 35 , 36 ]. Circ-HIPK3 sponges miR-338 and modulates the forkhead box AI axis to aggravate LPS-induced cell injury [ 34 ].…”

Circular RNAs in organ injury: recent development

“…Promotes fibroblast proliferation and lung fibroblast-to-myofibroblast transition [68] hsa_circ_0058493 upregulated Potential biomarker candiate [69] Silicosis circZC3H4 upregulated Regulates fibroblast activation and proliferation [71] Cigarette particle-induced lung injury circFOXO3 upregulated Promotes inflammatory response [74] circRNA_0006892 downregulated Promotes cell apoptosis and inflammatory response [75] Pulmonary hypertension circRNA_004592 upregulated Promotes cell proliferation and inhibits cell apoptosis [79] Acute lung injury hsa_circ_0059930 upregulated Inhibits cell apoptosis and inhibits cell proliferation [81] circRNA_0001679 upregulated Promotes cell apoptosis and proinflammatory cytokines [82] circHECTD1 downregulated Inhibits cell apoptosis [83] Kidney Mesangial cell Injury circLRP6 upregulated Promotes inflammatory response [33] Acute kidney injury circ_0114428 upregulated Promotes inflammatory response [90] circFANCA upregulated Promotes cell apoptosis, inflammatory response, oxidative stress [91] circ_RASGEF1B upregulated Promotes cell apoptosis and inflammatory response [92] circ_BNIP3L upregulated Promotes inflammatory response and oxidative stress [93] circ_0114427 upregulated Promotes inflammatory response [94] circSnrk upregulated Promotes cell apoptosis [27] hsa_circ_010157 upregulated Promotes cell apoptosis and inflammatory response [95] circTLK1 upregulated Promotes cell apoptosis, inflammatory response, oxidative stress [96] circHIPK3 upregulated Promotes cell apoptosis and inflammatory response from circRNAs derived from the extracellular exosomes of TBI-induced mouse brain. The study suggested that the extracellular circRNAs in brain-derived exosomes could involve in dendrite development and glutamatergic synapse formation [48].…”

“…In addition, multiple in vitro studies using LPS-induced AKI human kidney 2 (HK2) cell modes have reported a significantly upregulated expression profiles of numerous circRNAs that may contribute to promoting apoptosis and inflammatory response in AKI. Where circFANCA acted via the miR-93-5p/oxidative stress-responsive kinase 1 (OXSR1) axis [91]; circ_RASGEF1B acted via the miR-146a-5p/pyruvate dehydrogenase kinase 1 (Pdk1) axis [92]; circBNIP3L acted via the miR-370-3p/myeloid differentiation primary response 88 (MYD88) axis [93]; circ_0114427 acted via the miR-495-3p/TNF receptorassociated factor 6 (TRAF6) axis [94]; circSnrk acted via the MAPK axis [27]; hsa_circ_010157 (circSTRN3) acted via the miR-578/TLR4 axis [95]. Apart from in vitro studies, [101]also identified circTLK1 to be significantly upregulated in vivo.…”

The Intersection of Acute Kidney Injury and Non-Coding RNAs: Inflammation

“…Another study showed that the circRNA TLK1 indirectly enhances HMGB1 expression by sponging miRNA-106a-5p, thus aggravating the sepsis-induced inflammatory response in renal tubular epithelial cells ( Xu H.-P. et al, 2021 ). A study on the up-regulation of circ_0114427 in sepsis in AKI showed that it promoted the apoptosis of renal tubular epithelial cells and inflammatory response by targeting miRNA-495-3p to activate the TRAF6/NF-κB signaling pathway ( Xu et al, 2022 ). Additionally, it has been shown that circRNA HIPK3 aggravates LPS-induced inflammation via the miRNA-338/FOXA1 axis ( Lu et al, 2022 ).…”