Long non-coding RNA Mirt2 relieves lipopolysaccharide-induced injury in PC12 cells by suppressing miR-429

被引:20
作者
Li, Haibo [1 ]
Xu, Yu [1 ]
Wang, Guoxiu [2 ]
Chen, Xuerong [1 ]
Liang, Wenqing [1 ]
Ni, Huawei [3 ]
机构
[1] Shaoxing Hosp Zhejiang Univ, Dept Orthopaed, Shaoxing Peoples Hosp, Shaoxing 312000, Peoples R China
[2] Shenzhen Univ, Dept Orthopaed, Gen Hosp, Shenzhen 518055, Peoples R China
[3] Hangzhou Noma Univ, Dept Orthopaed, Affiliated Hosp, 126 Wenzhou Rd, Hangzhou 310015, Zhejiang, Peoples R China
关键词
Mirt2; Spinal cord injury; miR-429; Inflammation; Apoptosis; SPINAL-CORD-INJURY; INFLAMMATORY RESPONSE; AXONAL REGENERATION; FUNCTIONAL RECOVERY; SCI; CONTRIBUTES; PATHWAY;
D O I
10.1007/s13105-019-00691-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play important roles in the pathogenesis of spinal cord injury (SCI). This study investigated the effects of lncRNA Mirt2 and miR-429 on lipopolysaccharide (LPS)-induced injuries in PC12 cells. Serum samples were collected from 36 patients with SCI and the healthy controls. The expression of lncRNA Mirt2 in serum samples was measured by qRT-PCR. The in vitro model of SCI was established by treating PC12 cells with LPS. The effects of lncRNA Mirt2 and miR-429 on the cell model were evaluated by CCK-8 assay, flow cytometry, western blot, qRT-PCR, and ELISA. Further, the activation of NF-kappa B and p38MAPK pathways was tested by western blot. LPS induced obvious cell injuries in PC12 cells, as cell viability was reduced, apoptosis rate was increased, caspase-3 and -9 were cleaved, and the release of TNF-alpha and IL-6 was induced. lncRNA Mirt2 was up-regulated in LPS-stimulated PC12 cells and serum samples derived from SCI patients. Overexpression of lncRNA Mirt2 protected PC12 cells against LPS-induced injuries. Further studies found that lncRNA Mirt2 acted as the molecular sponge of miR-429 and miR-34a-5p. lncRNA Mirt2 did not protect PC12 cells when miR-429 was overexpressed. Moreover, the inhibitory effects of lncRNA Mirt2 on NF-kappa B and p38MAPK pathways were abolished when miR-429 was overexpressed. lncRNA Mirt2 exerts protective effects in an in vitro model of SCI by down-regulating miR-429. This study shed light on the treatment of SCI by using the lncRNA-miRNA regulation network.
引用
收藏
页码:403 / 413
页数:11
相关论文
共 31 条
[1]   Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms [J].
Alizadeh, Arsalan ;
Dyck, Scott Matthew ;
Karimi-Abdolrezaee, Soheila .
FRONTIERS IN NEUROLOGY, 2019, 10
[2]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]   Spinal cord injury (SCI) -: Prehospital management [J].
Bernhard, M ;
Gries, A ;
Kremer, P ;
Böttiger, BW .
RESUSCITATION, 2005, 66 (02) :127-139
[4]  
Bethea JR, 1998, J NEUROSCI, V18, P3251
[5]   Incidence rates and populations at risk for spinal cord injury: A regional study [J].
Burke, DA ;
Linden, RD ;
Zhang, YP ;
Maiste, AC ;
Shields, CB .
SPINAL CORD, 2001, 39 (05) :274-278
[6]   The crosstalk between lncRNA and microRNA in cancer metastasis: orchestrating the epithelial-mesenchymal plasticity [J].
Cao, Ming-xin ;
Jiang, Ya-ping ;
Tang, Ya-ling ;
Liang, Xin-hua .
ONCOTARGET, 2017, 8 (07) :12472-12483
[7]   Repertoire of microglial and macrophage responses after spinal cord injury [J].
David, Samuel ;
Kroner, Antje .
NATURE REVIEWS NEUROSCIENCE, 2011, 12 (07) :388-399
[8]   miR-136-5p Regulates the Inflammatory Response by Targeting the IKK/NF-B/A20 Pathway After Spinal Cord Injury [J].
Deng, Guiying ;
Gao, Yunbing ;
Cen, Zhongxi ;
He, Jichen ;
Cao, Baichuan ;
Zeng, Gaofeng ;
Zong, Shaohui .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2018, 50 (02) :512-524
[9]   A pathophysiological view of the long non-coding RNA world [J].
Di Gesualdo, Federico ;
Capaccioli, Sergio ;
Lulli, Matteo .
ONCOTARGET, 2014, 5 (22) :10976-10996
[10]   Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury [J].
Donnelly, Dustin J. ;
Popovich, Phillip G. .
EXPERIMENTAL NEUROLOGY, 2008, 209 (02) :378-388