TY - JOUR
T1 - The Biomarker TCONS_00016233 Drives Septic AKI by Targeting the miR-22-3p/AIFM1 Signaling Axis
AU - Zhang, Pan
AU - Yi, Lei
AU - Qu, Siyuan
AU - Dai, Jinzhong
AU - Li, Xiaozhou
AU - Liu, Bohao
AU - Li, Huiling
AU - Ai, Kai
AU - Zheng, Peilin
AU - Qiu, Shuangfa
AU - Li, Yijian
AU - Wang, Yinhuai
AU - Xiang, Xudong
AU - Chai, Xiangping
AU - Dong, Zheng
AU - Zhang, Dongshan
N1 - Funding Information:
The National Natural Science Foundation of China (81870475, 81570646, and 81770951), Hunan Province Natural Science Foundation (2018JJ2568), and Youth Foundation of Hu'nan Scientific Committee (2017JJ1035) supported this study, as well as the Changsha Science and Technology Bureau Project (kq1901115).
Funding Information:
The National Natural Science Foundation of China ( 81870475 , 81570646 , and 81770951 ), Hunan Province Natural Science Foundation ( 2018JJ2568 ), and Youth Foundation of Hu’nan Scientific Committee ( 2017JJ1035 ) supported this study, as well as the Changsha Science and Technology Bureau Project ( kq1901115 ).
Publisher Copyright:
© 2020 The Author(s)
PY - 2020/3/6
Y1 - 2020/3/6
N2 - The prediction of mortality for septic acute kidney injury (AKI) has been assessed by a number of potential biomarkers, including long noncoding RNAs (lncRNAs). However, the validation of lncRNAs as biomarkers, particularly for the early stages of septic AKI, is still warranted. Our results indicate that the lncRNA TCONS_00016233 is upregulated in plasma of sepsis-associated non-AKI and AKI patients, but a higher cutoff threshold (9.5 × 105, copy number) provided a sensitivity of 71.9% and specificity of 89.6% for the detection of AKI. The plasma TCONS_00016233 was highly correlated with serum creatinine, tissue inhibitor metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP7), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and urinary TCONS_00016233. Lipopolysaccharide (LPS) induced the expression of lncRNA TCONS_00016233 via the Toll-like receptor 4 (TLR4)/p38 mitogen-activated protein kinase (MAPK) signal pathway in human renal tubular epithelial (HK-2) cells. Furthermore, TCONS_00016233 mediates the LPS-induced HK-2 cell apoptosis and the expression of IL-1β and TNF-α. Mechanistically, TCONS_00016233 acts as a competing endogenous RNA (ceRNA) to prevent microRNA (miR)-22-3p-mediated downregulation of the apoptosis-inducing factor mitochondrion-associated 1 (AIFM1). Finally, overexpression of TCONS_00016233 is capable of aggravating the LPS- and cecal ligation and puncture (CLP)-induced septic AKI by targeting the miR-22-3p/AIFM1 axis. Taken together, our data indicate that TCONS_00016233 may serve as an early diagnosis marker for the septic AKI, possibly acting as a novel therapeutic target for septic AKI.
AB - The prediction of mortality for septic acute kidney injury (AKI) has been assessed by a number of potential biomarkers, including long noncoding RNAs (lncRNAs). However, the validation of lncRNAs as biomarkers, particularly for the early stages of septic AKI, is still warranted. Our results indicate that the lncRNA TCONS_00016233 is upregulated in plasma of sepsis-associated non-AKI and AKI patients, but a higher cutoff threshold (9.5 × 105, copy number) provided a sensitivity of 71.9% and specificity of 89.6% for the detection of AKI. The plasma TCONS_00016233 was highly correlated with serum creatinine, tissue inhibitor metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP7), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and urinary TCONS_00016233. Lipopolysaccharide (LPS) induced the expression of lncRNA TCONS_00016233 via the Toll-like receptor 4 (TLR4)/p38 mitogen-activated protein kinase (MAPK) signal pathway in human renal tubular epithelial (HK-2) cells. Furthermore, TCONS_00016233 mediates the LPS-induced HK-2 cell apoptosis and the expression of IL-1β and TNF-α. Mechanistically, TCONS_00016233 acts as a competing endogenous RNA (ceRNA) to prevent microRNA (miR)-22-3p-mediated downregulation of the apoptosis-inducing factor mitochondrion-associated 1 (AIFM1). Finally, overexpression of TCONS_00016233 is capable of aggravating the LPS- and cecal ligation and puncture (CLP)-induced septic AKI by targeting the miR-22-3p/AIFM1 axis. Taken together, our data indicate that TCONS_00016233 may serve as an early diagnosis marker for the septic AKI, possibly acting as a novel therapeutic target for septic AKI.
KW - AIFM1
KW - TCONS_00016233
KW - miR-22-3p
KW - septic AKI
UR - http://www.scopus.com/inward/record.url?scp=85079133832&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079133832&partnerID=8YFLogxK
U2 - 10.1016/j.omtn.2019.12.037
DO - 10.1016/j.omtn.2019.12.037
M3 - Article
AN - SCOPUS:85079133832
SN - 2162-2531
VL - 19
SP - 1027
EP - 1042
JO - Molecular Therapy - Nucleic Acids
JF - Molecular Therapy - Nucleic Acids
ER -
