miR-148b-3p promotes migration of Schwann cells by targeting cullin-associated and neddylationdissociated 1
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摘要
MicroRNAs(miRNAs) are small,non-coding RNAs that negatively adjust gene expression in multifarious biological processes.However,the regulatory effects of miRNAs on Schwann cells remain poorly understood.Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction,thereby affecting proliferation and migration of Schwann cells.This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1(Cand1).Up-regulated expression of miR-148b-3p promoted Schwann cell migration,whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro.Further experiments confirmed that Candl was a direct target of miR-148b-3p,and Candl knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration.These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Candl in vitro.
MicroRNAs(miRNAs) are small,non-coding RNAs that negatively adjust gene expression in multifarious biological processes.However,the regulatory effects of miRNAs on Schwann cells remain poorly understood.Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction,thereby affecting proliferation and migration of Schwann cells.This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1(Cand1).Up-regulated expression of miR-148b-3p promoted Schwann cell migration,whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro.Further experiments confirmed that Candl was a direct target of miR-148b-3p,and Candl knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration.These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Candl in vitro.
MicroRNAs(miRNAs) are small,non-coding RNAs that negatively adjust gene expression in multifarious biological processes.However,the regulatory effects of miRNAs on Schwann cells remain poorly understood.Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction,thereby affecting proliferation and migration of Schwann cells.This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1(Cand1).Up-regulated expression of miR-148b-3p promoted Schwann cell migration,whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro.Further experiments confirmed that Candl was a direct target of miR-148b-3p,and Candl knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration.These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Candl in vitro.
引文
Aure MR,Leivonen SK,Fleischer T,Zhu Q,Overgaard J,Alsner J,Tramm T,Louhimo R,Alnaes GI,Perala M,Busato F,Touleimat N,Tost J,Borresen-Dale AL,Hautaniemi S,Troyanskaya OG,Lingjaerde OC,Sahlberg KK,Kristensen VN(2013)Individual and combined effects of DNA methylation and copy number alterations on mi RNAexpression in breast tumors.Genome Biol 14:R126.
Bartel DP(2009)Micro RNAs:target recognition and regulatory functions.Cell 136:215-233.
Bremer J,O’Connor T,Tiberi C,Rehrauer H,Weis J,Aguzzi A(2010)Ablation of Dicer from murine Schwann cells increases their proliferation while blocking myelination.PLo S One 5:e12450.
Carthew RW,Sontheimer EJ(2009)Origins and Mechanisms of mi R-NAs and si RNAs.Cell 136:642-655.
De Pietri Tonelli D,Pulvers JN,Haffner C,Murchison EP,Hannon GJ,Huttner WB(2008)mi RNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex.Development 135:3911-3921.
Faghihi MA,Zhang M,Huang J,Modarresi F,Van der Brug MP,Nalls MA,Cookson MR,St-Laurent G 3rd,Wahlestedt C(2010)Evidence for natural antisense transcript-mediated inhibition of micro RNAfunction.Genome Biol 11:R56.
Filipowicz W,Bhattacharyya SN,Sonenberg N(2008)Mechanisms of post-transcriptional regulation by micro RNAs:are the answers in sight?Nat Rev Genet 9:102-114.
Jiang X,Du L,Wang L,Li J,Liu Y,Zheng G,Qu A,Zhang X,Pan H,Yang Y,Wang C(2015)Serum micro RNA expression signatures identified from genome-wide micro RNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer.Int J Cancer 136:854-862.
Junn E,Lee KW,Jeong BS,Chan TW,Im JY,Mouradian MM(2009)Repression of alpha-synuclein expression and toxicity by micro R-NA-7.Proc Natl Acad Sci U S A 106:13052-13057.
Kim AH,Reimers M,Maher B,Williamson V,Mc Michael O,Mc Clay JL,van den Oord EJ,Riley BP,Kendler KS,Vladimirov VI(2010)Micro RNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders.Schizophr Res124:183-191.
Kury P,Stoll G,Muller HW(2001)Molecular mechanisms of cellular interactions in peripheral nerve regeneration.Curr Opin Neurol14:635-639.
Li S,Wang X,Gu Y,Chen C,Wang Y,Liu J,Hu W,Yu B,Wang Y,Ding F,Liu Y,Gu X(2015)Let-7 micro RNAs regenerate peripheral nerve regeneration by targeting nerve growth factor.Mol Ther 23:423-433.
Liu Q,Xu Y,Wei S,Gao W,Chen L,Zhou T,Wang Z,Ying M,Zheng Q(2015)micro RNA-148b suppresses hepatic cancer stem cell by targeting neuropilin-1.Biosci Rep 35:e00229.
Livak KJ,Schmittgen TD(2001)Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))Method.Methods 25:402-408.
Lu A,Huang Z,Zhang C,Zhang X,Zhao J,Zhang H,Zhang Q,Wu S,Yi X(2014)Differential expression of microR NAs in dorsal root ganglia after sciatic nerve injury.Neural Regen Res 9:1031-1040.
Mantuano E,Inoue G,Li X,Takahashi K,Gaultier A,Gonias SL,Campana WM(2008)The hemopexin domain of matrix metalloproteinase-9 activates cell signaling and promotes migration of schwann cells by binding to low-density lipoprotein receptor-related protein.JNeurosci 28:11571-11582.
Murata T,Takayama K,Katayama S,Urano T,Horie-Inoue K,Ikeda K,Takahashi S,Kawazu C,Hasegawa A,Ouchi Y,Homma Y,Hayashizaki Y,Inoue S(2010)mi R-148a is an androgen-responsive micro RNAthat promotes LNCa P prostate cell growth by repressing its target CAND1 expression.Prostate Cancer Prostatic Dis 13:356-361.
Navarro X,Vivo M,Valero-Cabre A(2007)Neural plasticity after peripheral nerve injury and regeneration.Prog Neurobiol 82:163-201.
Ngeow WC(2010)Scar less:a review of methods of scar reduction at sites of peripheral nerve repair.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:357-366.
Pereira JA,Baumann R,Norrmen C,Somandin C,Miehe M,Jacob C,Luhmann T,Hall-Bozic H,Mantei N,Meijer D,Suter U(2010)Dicer in Schwann cells is required for myelination and axonal integrity.JNeurosci 30:6763-6775.
Santarelli DM,Beveridge NJ,Tooney PA,Cairns MJ(2011)Upregulation of dicer and micro RNA expression in the dorsolateral prefrontal cortex Brodmann area 46 in schizophrenia.Biol Psychiatry 69:180-187.
Verrier JD,Semple-Rowland S,Madorsky I,Papin JE,Notterpek L(2010)Reduction of Dicer impairs Schwann cell differentiation and myelination.J Neurosci Res 88:2558-2568.
Wang G,van der Walt JM,Mayhew G,Li YJ,Zuchner S,Scott WK,Martin ER,Vance JM(2008)Variation in the mi RNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein.Am J Hum Genet 82:283-289.
Wu D,Murashov AK(2013)Molecular mechanisms of peripheral nerve regeneration:emerging roles of micro RNAs.Front Physiol 4:55.
Yu B,Zhou S,Wang Y,Ding G,Ding F,Gu X(2011)Profile of micro R-NAs following rat sciatic nerve injury by deep sequencing:implication for mechanisms of nerve regeneration.PLo S One 6:e24612.
Yu B,Qian T,Wang Y,Zhou S,Ding G,Ding F,Gu X(2012a)mi R-182inhibits Schwann cell proliferation and migration by targeting FGF9and NTM,respectively at an early stage following sciatic nerve injury.Nucleic Acids Res 40:10356-10365.
Yu B,Zhou S,Wang Y,Qian T,Ding G,Ding F,Gu X(2012b)mi R-221and mi R-222 promote Schwann cell proliferation and migration by targeting LASS2 after sciatic nerve injury.J Cell Sci 125:2675-2683.
Zemla A,Thomas Y,Kedziora S,Knebel A,Wood NT,Rabut G,Kurz T(2013)CSN-and CAND1-dependent remodelling of the budding yeast SCF complex.Nat Commun 4:1641.
Zhang JG,Shi Y,Hong DF,Song M,Huang D,Wang CY,Zhao G(2015)MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/beta-catenin pathway.Sci Rep 5:8087.
Zhou S,Gao R,Hu W,Qian T,Wang N,Ding G,Ding F,Yu B,Gu X(2014)Mi R-9 inhibits Schwann cell migration by targeting Cthrc1following sciatic nerve injury.J Cell Sci 127:967-976.
Zou H,Ho C,Wong K,Tessier-Lavigne M(2009)Axotomy-induced Smad1 activation promotes axonal growth in adult sensory neurons.J Neurosci 29:7116-7123.
Bartel DP(2009)Micro RNAs:target recognition and regulatory functions.Cell 136:215-233.
Bremer J,O’Connor T,Tiberi C,Rehrauer H,Weis J,Aguzzi A(2010)Ablation of Dicer from murine Schwann cells increases their proliferation while blocking myelination.PLo S One 5:e12450.
Carthew RW,Sontheimer EJ(2009)Origins and Mechanisms of mi R-NAs and si RNAs.Cell 136:642-655.
De Pietri Tonelli D,Pulvers JN,Haffner C,Murchison EP,Hannon GJ,Huttner WB(2008)mi RNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex.Development 135:3911-3921.
Faghihi MA,Zhang M,Huang J,Modarresi F,Van der Brug MP,Nalls MA,Cookson MR,St-Laurent G 3rd,Wahlestedt C(2010)Evidence for natural antisense transcript-mediated inhibition of micro RNAfunction.Genome Biol 11:R56.
Filipowicz W,Bhattacharyya SN,Sonenberg N(2008)Mechanisms of post-transcriptional regulation by micro RNAs:are the answers in sight?Nat Rev Genet 9:102-114.
Jiang X,Du L,Wang L,Li J,Liu Y,Zheng G,Qu A,Zhang X,Pan H,Yang Y,Wang C(2015)Serum micro RNA expression signatures identified from genome-wide micro RNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer.Int J Cancer 136:854-862.
Junn E,Lee KW,Jeong BS,Chan TW,Im JY,Mouradian MM(2009)Repression of alpha-synuclein expression and toxicity by micro R-NA-7.Proc Natl Acad Sci U S A 106:13052-13057.
Kim AH,Reimers M,Maher B,Williamson V,Mc Michael O,Mc Clay JL,van den Oord EJ,Riley BP,Kendler KS,Vladimirov VI(2010)Micro RNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders.Schizophr Res124:183-191.
Kury P,Stoll G,Muller HW(2001)Molecular mechanisms of cellular interactions in peripheral nerve regeneration.Curr Opin Neurol14:635-639.
Li S,Wang X,Gu Y,Chen C,Wang Y,Liu J,Hu W,Yu B,Wang Y,Ding F,Liu Y,Gu X(2015)Let-7 micro RNAs regenerate peripheral nerve regeneration by targeting nerve growth factor.Mol Ther 23:423-433.
Liu Q,Xu Y,Wei S,Gao W,Chen L,Zhou T,Wang Z,Ying M,Zheng Q(2015)micro RNA-148b suppresses hepatic cancer stem cell by targeting neuropilin-1.Biosci Rep 35:e00229.
Livak KJ,Schmittgen TD(2001)Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))Method.Methods 25:402-408.
Lu A,Huang Z,Zhang C,Zhang X,Zhao J,Zhang H,Zhang Q,Wu S,Yi X(2014)Differential expression of microR NAs in dorsal root ganglia after sciatic nerve injury.Neural Regen Res 9:1031-1040.
Mantuano E,Inoue G,Li X,Takahashi K,Gaultier A,Gonias SL,Campana WM(2008)The hemopexin domain of matrix metalloproteinase-9 activates cell signaling and promotes migration of schwann cells by binding to low-density lipoprotein receptor-related protein.JNeurosci 28:11571-11582.
Murata T,Takayama K,Katayama S,Urano T,Horie-Inoue K,Ikeda K,Takahashi S,Kawazu C,Hasegawa A,Ouchi Y,Homma Y,Hayashizaki Y,Inoue S(2010)mi R-148a is an androgen-responsive micro RNAthat promotes LNCa P prostate cell growth by repressing its target CAND1 expression.Prostate Cancer Prostatic Dis 13:356-361.
Navarro X,Vivo M,Valero-Cabre A(2007)Neural plasticity after peripheral nerve injury and regeneration.Prog Neurobiol 82:163-201.
Ngeow WC(2010)Scar less:a review of methods of scar reduction at sites of peripheral nerve repair.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:357-366.
Pereira JA,Baumann R,Norrmen C,Somandin C,Miehe M,Jacob C,Luhmann T,Hall-Bozic H,Mantei N,Meijer D,Suter U(2010)Dicer in Schwann cells is required for myelination and axonal integrity.JNeurosci 30:6763-6775.
Santarelli DM,Beveridge NJ,Tooney PA,Cairns MJ(2011)Upregulation of dicer and micro RNA expression in the dorsolateral prefrontal cortex Brodmann area 46 in schizophrenia.Biol Psychiatry 69:180-187.
Verrier JD,Semple-Rowland S,Madorsky I,Papin JE,Notterpek L(2010)Reduction of Dicer impairs Schwann cell differentiation and myelination.J Neurosci Res 88:2558-2568.
Wang G,van der Walt JM,Mayhew G,Li YJ,Zuchner S,Scott WK,Martin ER,Vance JM(2008)Variation in the mi RNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein.Am J Hum Genet 82:283-289.
Wu D,Murashov AK(2013)Molecular mechanisms of peripheral nerve regeneration:emerging roles of micro RNAs.Front Physiol 4:55.
Yu B,Zhou S,Wang Y,Ding G,Ding F,Gu X(2011)Profile of micro R-NAs following rat sciatic nerve injury by deep sequencing:implication for mechanisms of nerve regeneration.PLo S One 6:e24612.
Yu B,Qian T,Wang Y,Zhou S,Ding G,Ding F,Gu X(2012a)mi R-182inhibits Schwann cell proliferation and migration by targeting FGF9and NTM,respectively at an early stage following sciatic nerve injury.Nucleic Acids Res 40:10356-10365.
Yu B,Zhou S,Wang Y,Qian T,Ding G,Ding F,Gu X(2012b)mi R-221and mi R-222 promote Schwann cell proliferation and migration by targeting LASS2 after sciatic nerve injury.J Cell Sci 125:2675-2683.
Zemla A,Thomas Y,Kedziora S,Knebel A,Wood NT,Rabut G,Kurz T(2013)CSN-and CAND1-dependent remodelling of the budding yeast SCF complex.Nat Commun 4:1641.
Zhang JG,Shi Y,Hong DF,Song M,Huang D,Wang CY,Zhao G(2015)MiR-148b suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting WNT1/beta-catenin pathway.Sci Rep 5:8087.
Zhou S,Gao R,Hu W,Qian T,Wang N,Ding G,Ding F,Yu B,Gu X(2014)Mi R-9 inhibits Schwann cell migration by targeting Cthrc1following sciatic nerve injury.J Cell Sci 127:967-976.
Zou H,Ho C,Wong K,Tessier-Lavigne M(2009)Axotomy-induced Smad1 activation promotes axonal growth in adult sensory neurons.J Neurosci 29:7116-7123.