lncRNA-Map2k4 sequesters miR-199a to promote FGF1 expression and spinal cord neuron growth

Spinal cord injury (SCI) is a common critical illness in clinical practice. SCI prevention, treatment and rehabilitation have become important topics in today's medical profession. Studies have shown that long noncoding RNAs (lncRNAs) also play an important role in the pathology of SCI. The bio...

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Veröffentlicht in:Biochemical and biophysical research communications 2017-08, Vol.490 (3), p.948-954
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description Spinal cord injury (SCI) is a common critical illness in clinical practice. SCI prevention, treatment and rehabilitation have become important topics in today's medical profession. Studies have shown that long noncoding RNAs (lncRNAs) also play an important role in the pathology of SCI. The biology software analysis identified miR-199a binding sites in the lncRNA-Map2k4 and FGF1 sequences, which were confirmed by the subsequent dual luciferase reporter assay. When lncRNA-Map2k4 expression was down-regulated by siRNA, miR-199a expression in neurons was up-regulated and FGF1 expression was down-regulated. In turn, miR-199a up-regulation inhibited lncRNA-Map2k4 and FGF1 expression. But when lncRNA-Map2k4-m (a lncRNA-Map2k4 overexpression vector with mutated miR-199a binding sites) was co-transfected into neuronal cells with miR-199a mimics, lncRNA-Map2k4-m over-expression did not block the inhibition of FGF1 expression by miR-199a. Moreover, lncRNA-Map2k4 and FGF1 promoted the proliferation and inhibited the apoptosis of neuronal cells, whereas miR-199a down-regulated the aforementioned functions of lncRNA-Map2k4 and FGF1; however, lncRNA-Map2k4-m could not block the inhibitory action of miR-199a on proliferation. Thus, lncRNA-Map2k4 regulates neuronal proliferation and apoptosis through a miR-199a/FGF1 pathway. This finding provides more evidence for the role of lncRNAs in SCI. •lncRNA-Map2k4 is the target gene of miR-199a, and its down-regulation promotes miR-199a expression in neurons.•miR-199a targeted regulation of FGF1 expression in neurons.•Knockdown of lncRNA-Map2k4 inhibited the FGF1 expression by up-regulating miR-199a.•lncRNA-Map2k4 regulates neuron proliferation and apoptosis through an miR-199a/FGF1 pathway.
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SCI prevention, treatment and rehabilitation have become important topics in today's medical profession. Studies have shown that long noncoding RNAs (lncRNAs) also play an important role in the pathology of SCI. The biology software analysis identified miR-199a binding sites in the lncRNA-Map2k4 and FGF1 sequences, which were confirmed by the subsequent dual luciferase reporter assay. When lncRNA-Map2k4 expression was down-regulated by siRNA, miR-199a expression in neurons was up-regulated and FGF1 expression was down-regulated. In turn, miR-199a up-regulation inhibited lncRNA-Map2k4 and FGF1 expression. But when lncRNA-Map2k4-m (a lncRNA-Map2k4 overexpression vector with mutated miR-199a binding sites) was co-transfected into neuronal cells with miR-199a mimics, lncRNA-Map2k4-m over-expression did not block the inhibition of FGF1 expression by miR-199a. 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This finding provides more evidence for the role of lncRNAs in SCI. •lncRNA-Map2k4 is the target gene of miR-199a, and its down-regulation promotes miR-199a expression in neurons.•miR-199a targeted regulation of FGF1 expression in neurons.•Knockdown of lncRNA-Map2k4 inhibited the FGF1 expression by up-regulating miR-199a.•lncRNA-Map2k4 regulates neuron proliferation and apoptosis through an miR-199a/FGF1 pathway.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2017.06.145</identifier><identifier>PMID: 28655615</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Animals ; APOPTOSIS ; Cell Proliferation ; Cells, Cultured ; Down-Regulation ; FGF1 ; Fibroblast Growth Factor 1 - genetics ; Gene Expression Regulation ; INHIBITION ; INJURIES ; lncRNA ; lncRNA-Map2k4 ; LUCIFERASE ; Mice, Inbred C57BL ; MicroRNAs - genetics ; miR-199a ; NERVE CELLS ; Neurogenesis ; Neuron ; Neurons - cytology ; Neurons - metabolism ; PATHOLOGY ; PLANT GROWTH ; RNA ; RNA, Long Noncoding - genetics ; SPINAL CORD ; Spinal Cord - cytology ; Spinal Cord Injuries - genetics ; Spinal cord injury ; Up-Regulation</subject><ispartof>Biochemical and biophysical research communications, 2017-08, Vol.490 (3), p.948-954</ispartof><rights>2017</rights><rights>Copyright © 2017. 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SCI prevention, treatment and rehabilitation have become important topics in today's medical profession. Studies have shown that long noncoding RNAs (lncRNAs) also play an important role in the pathology of SCI. The biology software analysis identified miR-199a binding sites in the lncRNA-Map2k4 and FGF1 sequences, which were confirmed by the subsequent dual luciferase reporter assay. When lncRNA-Map2k4 expression was down-regulated by siRNA, miR-199a expression in neurons was up-regulated and FGF1 expression was down-regulated. In turn, miR-199a up-regulation inhibited lncRNA-Map2k4 and FGF1 expression. But when lncRNA-Map2k4-m (a lncRNA-Map2k4 overexpression vector with mutated miR-199a binding sites) was co-transfected into neuronal cells with miR-199a mimics, lncRNA-Map2k4-m over-expression did not block the inhibition of FGF1 expression by miR-199a. Moreover, lncRNA-Map2k4 and FGF1 promoted the proliferation and inhibited the apoptosis of neuronal cells, whereas miR-199a down-regulated the aforementioned functions of lncRNA-Map2k4 and FGF1; however, lncRNA-Map2k4-m could not block the inhibitory action of miR-199a on proliferation. Thus, lncRNA-Map2k4 regulates neuronal proliferation and apoptosis through a miR-199a/FGF1 pathway. This finding provides more evidence for the role of lncRNAs in SCI. •lncRNA-Map2k4 is the target gene of miR-199a, and its down-regulation promotes miR-199a expression in neurons.•miR-199a targeted regulation of FGF1 expression in neurons.•Knockdown of lncRNA-Map2k4 inhibited the FGF1 expression by up-regulating miR-199a.•lncRNA-Map2k4 regulates neuron proliferation and apoptosis through an miR-199a/FGF1 pathway.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Animals</subject><subject>APOPTOSIS</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Down-Regulation</subject><subject>FGF1</subject><subject>Fibroblast Growth Factor 1 - genetics</subject><subject>Gene Expression Regulation</subject><subject>INHIBITION</subject><subject>INJURIES</subject><subject>lncRNA</subject><subject>lncRNA-Map2k4</subject><subject>LUCIFERASE</subject><subject>Mice, Inbred C57BL</subject><subject>MicroRNAs - genetics</subject><subject>miR-199a</subject><subject>NERVE CELLS</subject><subject>Neurogenesis</subject><subject>Neuron</subject><subject>Neurons - 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genetics</topic><topic>Gene Expression Regulation</topic><topic>INHIBITION</topic><topic>INJURIES</topic><topic>lncRNA</topic><topic>lncRNA-Map2k4</topic><topic>LUCIFERASE</topic><topic>Mice, Inbred C57BL</topic><topic>MicroRNAs - genetics</topic><topic>miR-199a</topic><topic>NERVE CELLS</topic><topic>Neurogenesis</topic><topic>Neuron</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>PATHOLOGY</topic><topic>PLANT GROWTH</topic><topic>RNA</topic><topic>RNA, Long Noncoding - genetics</topic><topic>SPINAL CORD</topic><topic>Spinal Cord - cytology</topic><topic>Spinal Cord Injuries - genetics</topic><topic>Spinal cord injury</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lv, Hao-ran</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - 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SCI prevention, treatment and rehabilitation have become important topics in today's medical profession. Studies have shown that long noncoding RNAs (lncRNAs) also play an important role in the pathology of SCI. The biology software analysis identified miR-199a binding sites in the lncRNA-Map2k4 and FGF1 sequences, which were confirmed by the subsequent dual luciferase reporter assay. When lncRNA-Map2k4 expression was down-regulated by siRNA, miR-199a expression in neurons was up-regulated and FGF1 expression was down-regulated. In turn, miR-199a up-regulation inhibited lncRNA-Map2k4 and FGF1 expression. But when lncRNA-Map2k4-m (a lncRNA-Map2k4 overexpression vector with mutated miR-199a binding sites) was co-transfected into neuronal cells with miR-199a mimics, lncRNA-Map2k4-m over-expression did not block the inhibition of FGF1 expression by miR-199a. Moreover, lncRNA-Map2k4 and FGF1 promoted the proliferation and inhibited the apoptosis of neuronal cells, whereas miR-199a down-regulated the aforementioned functions of lncRNA-Map2k4 and FGF1; however, lncRNA-Map2k4-m could not block the inhibitory action of miR-199a on proliferation. Thus, lncRNA-Map2k4 regulates neuronal proliferation and apoptosis through a miR-199a/FGF1 pathway. This finding provides more evidence for the role of lncRNAs in SCI. •lncRNA-Map2k4 is the target gene of miR-199a, and its down-regulation promotes miR-199a expression in neurons.•miR-199a targeted regulation of FGF1 expression in neurons.•Knockdown of lncRNA-Map2k4 inhibited the FGF1 expression by up-regulating miR-199a.•lncRNA-Map2k4 regulates neuron proliferation and apoptosis through an miR-199a/FGF1 pathway.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28655615</pmid><doi>10.1016/j.bbrc.2017.06.145</doi><tpages>7</tpages></addata></record>
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subjects 60 APPLIED LIFE SCIENCES
Animals
APOPTOSIS
Cell Proliferation
Cells, Cultured
Down-Regulation
FGF1
Fibroblast Growth Factor 1 - genetics
Gene Expression Regulation
INHIBITION
INJURIES
lncRNA
lncRNA-Map2k4
LUCIFERASE
Mice, Inbred C57BL
MicroRNAs - genetics
miR-199a
NERVE CELLS
Neurogenesis
Neuron
Neurons - cytology
Neurons - metabolism
PATHOLOGY
PLANT GROWTH
RNA
RNA, Long Noncoding - genetics
SPINAL CORD
Spinal Cord - cytology
Spinal Cord Injuries - genetics
Spinal cord injury
Up-Regulation
title lncRNA-Map2k4 sequesters miR-199a to promote FGF1 expression and spinal cord neuron growth
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