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Severe hydronephrosis increases the risk of urinary tract infection and irretrievable renal fibrosis. While TGFβ1-mediated fibrotic changes in proximal tubular epithelial cells and fatty acid oxidation (FAO) deregulation contribute to renal fibrosis and hydronephrosis. Firstly, a few elements were analyzed in this paper, including differentially-expressed long non-coding RNAs (lncRNAs), and miRNAs correlated to CPT1A, RXRA, and NCOA1. This paper investigated TGFβ1 effects on lncRNA FABP5P3, CPT1A, RXRA, and NCOA1 expression and fibrotic changes in HK-2 cells and FABP5P3 overexpression effects on TGFβ1-induced changes. Moreover, this paper predicted and proved that miR-22 binding to lncRNA FABP5P3, 3'UTR of CPT1A, RXRA, and NCOA1 was validated. The dynamic effects of the FABP5P3/miR-22 axis on TGFβ1-induced changes were investigated. A Renal fibrosis model was established in unilateral ureteral obstruction (UUO) mice, and FABP5P3 effects were investigated. Eventually, this paper concluded that TGFβ1 inhibited lncRNA FABP5P3, CPT1A, RXRA, and NCOA1 expression, induced fibrotic changes in HK-2 cells, and induced metabolic reprogramming within HK-2 cells, especially lower FAO. FABP5P3 overexpression partially reversed TGFβ1-induced changes. miR-22 targeted lncRNA FABP5P3, CPT1A, RXRA, and NCOA1. LncRNA FABP5P3 counteracted miR-22 inhibition of CPT1A, NCOA1, and RXRA through competitive binding. TGFβ1 stimulation induced the activation of TGFβ/SMAD and JAG/Notch signaling pathways; Nocth2 knockdown reversed TGFβ1 suppression on lncRNA FABP5P3. FABP5P3 overexpression attenuated renal fibrosis in unilateral ureteral obstruction mice. The LncRNA FABP5P3/miR-22 axis might be a potent target for improving the FAO deregulation and fibrotic changes in proximal TECs under TGFβ1 stimulation.

Introduction: Cervical squamous cell carcinoma (CESC) is the most common gynecological malignancy worldwide. Although the cancer susceptibility 18 (CASC18) gene was involved in the regulation of cancer biology, its specific role in CESC is not well characterized., Methods: CASC18 -related axis was predicted by bioinformatic analyses, and the competing endogenous RNA (ceRNA) interaction was further validated using quantitative real-time PCR, western blotting, RNA pulldown, and luciferase reporter assays. Transwell and wound healing assays were performed to verify the effect of CASC18 on SiHa and HeLa cell motility., Results: We found that CASC18 was upregulated in CESC tissues. Moreover, interference with CASC18 attenuated NUAK1 -mediated epithelial-mesenchymal transition (EMT) and thus suppressed cancer cell motility. Furthermore, the effects of CASC18 knockdown on CESC cells were partly rescued by transfection with the miR-5586-5p inhibitor. Additionally, our findings indicated that CASC18 acts as a ceRNA to enhance NUAK1 expression by sponging miR-5586-5p., Conclusion: Our study showed a novel CASC18 /miR-5586-5p/ NUAK1 ceRNA axis that could regulate cell invasion and migration by modulating EMT in CESC. These findings suggest that CASC18 may potentially serve as a novel therapeutic target in CESC treatment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We recently identified oncologic miR-182 as a new regulator of pulmonary artery hypertension (PAH) that targets myeloid-associated differentiation marker (Myadm), which is expressed in bone marrow stem cells and multipotent progenitors. Both miR-182 and Myadm are expressed in the cardiopulmonary system and correlated with the balance between the bone morphogenetic protein (BMP) and the transforming growth factor (TGF)-β signalling pathways, which are disturbed in PAH. We hypothesize that miR-182/Myadm are involved in BMP-TGF-β-signalling way in PAH. Hypoxia triggered pathological progression in cardiopulmonary PAH in vivo and in vitro; these changes were accompanied by strongly dowregulated BMP/SMAD1/5/8 expression and enhanced TGF-β/SMAD2/3 signalling pathway, favouring SMAD4/SMAD2 transcript formation and inhibiting the PAH negative regulator Id1 expression. miR-182 gain-of-function significantly inhibited the pathological progression in hypoxia-induced PAH (HPH) in vivo and in vitro, with a restoration of the balance in BMP-TGF-β signalling pathway. This recovery was abrogated by overexpression of Myadm. Conversely, loss-of-function of miR-182 increased the pathological progression of HPH followed by severe disturbance of BMP and TGF-β signal transduction and reduced Id1 expression, which was restored by Myadm knockdown. We also showed that the miR-182/Myadm relate BMP-TGF-β pathway is associated with NOS3/NO/cGMP via the crosstalk between endothelial cells and smooth muscle cells. Our findings further support the therapeutic significance of miR-182/Myadm in PAH via the balance of BMP- and TGF-β-associated mechanisms., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The present study aimed to investigate whether miR-129-5p can regulate high-mobility group box protein 1 (HMGB1)-modulated TLRs/NF-kappaB inflammatory pathway that contributed to lipopolysaccharide (LPS)-induced podocyte apoptosis and acutekidneyinjury (AKI)., Material and Methods: In vitro and in vivo models of sepsis were simulated using LPS-administrated podocytes and mice, respectively. The effects of LPS, mR-129-5p mimics and short hairpin RNA of HMGB1 (sh-HMGB1) on podocyte apoptosis were monitored using TUNEL staining. Protein expression was measured using western blotting. Survival outcomes were analyzed in septic mice with agomir-mR-129-5p administration., Results: We observed that stimulation of podocytes with LPS significantly inhibits the expression of miR-129-5p, and overexpression of miR-129-5p protects against LPS-induced podocyte damage, over-activation of inflammatory response and apoptosis. In a mouse model, agomir-miR-129-5p administration significantly improves the survival outcomes in septic mice and LPS-induced AKI. Mechanically, LPS-induced the elevation of HMGB1, TLR2, TLR4 and nuclear NF-κB protein expression in vitro and in vivo are restrained by the overexpression of miR-129-5p., Conclusions: Overexpression of miR-129-5p protects against LPS-induced podocyte apoptosis, inflammation and AKI in vivo and in vitro models of sepsis. The underlying molecular mechanism is mediated via attenuating HMGB1/TLRs/NF-κB signaling axis modulated inflammatory response., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Rationale: There is a continued need for investigating the roles of microRNAs and their targets on the pathogenesis of pulmonary arterial hypertension (PAH) vascular remodeling. We recently identified the association of myeloid miR-182-3p and its new target, Myeloid-Associated Differentiation Marker (Myadm), with vascular remodeling. Here, we aimed to determine the role of miR-182-3p/Myadm on PAH vascular remodeling and the underlying molecular mechanism. Methods: The miR-182-3p/Myadm expression profiles were detected in PAH patients and experimental rodent models. Loss-of-function and gain-of-function studies using gene knock-in or gene knock-out and the combinations of the proteomic technology and genome-wide ChIP-Seq were employed to determine the downstream targets of miR-182-3p/Myadm in response to monocrotaline (MCT)-induced PAH. Results: The miR-182-3p/Myadm expression was altered in PAH patients and experimental rodent models. Both miR-182-3p inhibitor and overexpression of Myadm augmented the pathological progression in rats in response to MCT-induced PAH. In contrast, miR-182-3p mimic and Myadm gene knockout attenuated the changes in the hemodynamics and structure of the cardio-pulmonary system in MCT-induced PAH in rats. Myadm mediated the proliferation of pulmonary artery smooth muscle cells (PASMCs) by altering the cell cycle kinase inhibitor (p21/Cip1) expression through the transcription factor Krüppel-like factor 4 (KLF4) translocation into the cytoplasm. Conclusion: Our findings indicate the prognostic and therapeutic significance of miR-182-3p in PAH and provide a new regulatory model of the myeloid-derived miR-182-3p/Myadm/KLF4/p21 axis in PAH vascular remodeling., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)