LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axis
Background: The abnormal expression of long non-coding RNA (lncRNA) Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) has been observed in many human cancers and the underlying mechanisms have been well studied. However, the function of OIP5-AS1 in acute kidney injury (AKI) remains unclear. Metho...
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Elsevier
2022-08-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2319417021000962 |
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author | Siyuan Chang Mingyang Chang Gang Liu Daqian Xu Haili Wang Rongqing Sun Min Feng |
author_facet | Siyuan Chang Mingyang Chang Gang Liu Daqian Xu Haili Wang Rongqing Sun Min Feng |
author_sort | Siyuan Chang |
collection | DOAJ |
description | Background: The abnormal expression of long non-coding RNA (lncRNA) Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) has been observed in many human cancers and the underlying mechanisms have been well studied. However, the function of OIP5-AS1 in acute kidney injury (AKI) remains unclear. Methods: To explore the role of OIP5-AS1 in the progression of AKI, the cisplatin-induced AKI mouse and cell model were established. To confirm the potential protective effect of OIP5-AS1 during cisplatin-induced AKI, rescue experiments were performed. Targetscan was used to predict the potential targets of miR-144-5p. To further determine whether the effect of miR-144-5p during cisplatin-induced AKI was mediated by PMK2, the recuse experiments using PMK2 overexpressing vector was applied. Results: OIP5-AS1 was significantly downregulated both in cisplatin-induced AKI mice and human renal tubular cell line HK-2 cells. Moreover, overexpression of OIP5-AS1 efficiently promoted cell growth and reduced cisplatin-induced apoptosis of HK-2 cells. Furthermore, OIP5-AS1 was identified as a sponge of miR-144-5p, and upregulation of miR-144-5p could significantly reverse overexpression of OIP5-AS1-induced protective effect on the damage of cisplatin to HK-2 cells. In addition, pyruvate kinase M2 (PKM2) was found to be a direct target of miR-144-5p, and overexpression of PKM2 efficiently reversed the effect of miR-144-5p mimics on the damage in cisplatin-stimulated HK-2 cells. Conclusions: OIP5-AS1 reduced the apoptosis of cisplatin-stimulated renal epithelial cells by targeting the miR-144-5p/PKM2 axis, which extended the regulatory network of lncRNAs in cisplatin-induced AKI and also provided a novel therapeutic target for AKI treatment. |
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spelling | doaj.art-de460044e6a24ec0b6f4a459b0cd23ec2022-12-22T01:52:18ZengElsevierBiomedical Journal2319-41702022-08-01454642653LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axisSiyuan Chang0Mingyang Chang1Gang Liu2Daqian Xu3Haili Wang4Rongqing Sun5Min Feng6Department of SICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, PR ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, PR ChinaDepartment of SICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, PR ChinaDepartment of SICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, PR ChinaDepartment of SICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, PR ChinaDepartment of SICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, PR ChinaDepartment of SICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, PR China; Corresponding author. Department of SICU, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Rd., Zhengzhou, Henan, 450001, PR China.Background: The abnormal expression of long non-coding RNA (lncRNA) Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) has been observed in many human cancers and the underlying mechanisms have been well studied. However, the function of OIP5-AS1 in acute kidney injury (AKI) remains unclear. Methods: To explore the role of OIP5-AS1 in the progression of AKI, the cisplatin-induced AKI mouse and cell model were established. To confirm the potential protective effect of OIP5-AS1 during cisplatin-induced AKI, rescue experiments were performed. Targetscan was used to predict the potential targets of miR-144-5p. To further determine whether the effect of miR-144-5p during cisplatin-induced AKI was mediated by PMK2, the recuse experiments using PMK2 overexpressing vector was applied. Results: OIP5-AS1 was significantly downregulated both in cisplatin-induced AKI mice and human renal tubular cell line HK-2 cells. Moreover, overexpression of OIP5-AS1 efficiently promoted cell growth and reduced cisplatin-induced apoptosis of HK-2 cells. Furthermore, OIP5-AS1 was identified as a sponge of miR-144-5p, and upregulation of miR-144-5p could significantly reverse overexpression of OIP5-AS1-induced protective effect on the damage of cisplatin to HK-2 cells. In addition, pyruvate kinase M2 (PKM2) was found to be a direct target of miR-144-5p, and overexpression of PKM2 efficiently reversed the effect of miR-144-5p mimics on the damage in cisplatin-stimulated HK-2 cells. Conclusions: OIP5-AS1 reduced the apoptosis of cisplatin-stimulated renal epithelial cells by targeting the miR-144-5p/PKM2 axis, which extended the regulatory network of lncRNAs in cisplatin-induced AKI and also provided a novel therapeutic target for AKI treatment.http://www.sciencedirect.com/science/article/pii/S2319417021000962OIP5-AS1miR-144-5pPKM2AKICell viabilityApoptosis |
spellingShingle | Siyuan Chang Mingyang Chang Gang Liu Daqian Xu Haili Wang Rongqing Sun Min Feng LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axis Biomedical Journal OIP5-AS1 miR-144-5p PKM2 AKI Cell viability Apoptosis |
title | LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axis |
title_full | LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axis |
title_fullStr | LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axis |
title_full_unstemmed | LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axis |
title_short | LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axis |
title_sort | lncrna oip5 as1 reduces renal epithelial cell apoptosis in cisplatin induced aki by regulating the mir 144 5p pkm2 axis |
topic | OIP5-AS1 miR-144-5p PKM2 AKI Cell viability Apoptosis |
url | http://www.sciencedirect.com/science/article/pii/S2319417021000962 |
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