Issue
MiRNA-214 promotes the pyroptosis and inhibits the proliferation of cervical cancer cells via regulating the expression of NLRP3
Corresponding Author(s) : Xuehui Bi
Cellular and Molecular Biology,
Vol. 66 No. 6: Issue 6
Abstract
Inflammasome mediates the maturation of interleukin-1β (IL-1β) and IL-18, triggers the pyroptosis and associates with multiple autoimmune diseases. In light of this, we hope to investigate the regulatory role of miRNA-214 in the inflammasome of cervical cancer. With the samples collected from 50 cervical cancer patients and 50 age-matched healthy subjects, real-time PCR and Western blotting were employed to detect the mRNA and/or protein expression profiles of the NOD-like receptor protein family, including NLRP1, NLRP3, NLRC4, Caspase-1, IL-1β, IL-18 and miR-214. Corresponding plasmids were used to transfect the Hela, HCC94, Siha or HUCEL normal cell lines to upregulate or downregulate the expression of targeted genes and to construct the cervical cancer models on rats. In addition, RT-PCR and Western blot were also considered to detect the expression of miR-214 and pyroptosis-related genes, while the pyroptosis of cells was evaluated by using the caspase-1 activity detection kit. Downregulation of miR-214 was found in the cervical cancer patients and the cervical cancer cell lines (** P <0.01), while overexpression of miR-214 could induce the pyroptosis of cervical cancer cell by targeting NLRP3. In cervical cancer patients, miR-214 and NLRP3 are downregulated, while upregulation of miR-214, by enhancing the expression of NLRP3, can advance the pyroptosis of cervical cancer cells. In addition, we, for the first time, clarify the correlation of cervical cancer with the miR-214 and NLRP3.
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- Hsieh VC, Chen ZJ, Liu CC, Chiang JH, Shieh SH, Hsieh MS. Forgone Health and Economic Benefits Associated with Socioeconomic Differences in Organized Cervical Cancer Screening. Asian Pac J Cancer Prev 2019; 20(12): 3755-3762.
- Kaur G, Balasubramaniam SD, Lee YJ. IGFBP-2 in cervical cancer development. Exp Mol Pathol. 2019: 104362.
- Zhang S, Wang W, Wu X, Liu W, Ding F. miR-16-5p modulates the radiosensitivity of cervical cancer cells via regulating coactivator-associated arginine methyltransferase 1. Pathol Int 2020; 70(1): 12-20.
- Wang YY, Wang ZJ, Zhang Y, Gao XH, Yang CX, Zhao FH, Qiao YL, Ma L, Lang JH. [Economic evaluation of fifteen cervical cancer screening strategies in rural China]. Zhonghua Fu Chan Ke Za Zhi. 2019; 54(12): 840-847.
- Zhou J, Zhang Y, Zou X, Kuai L, Wang L, Wang J, Shen F, Hu J, Zhang X, Huang Y, Chen Y. Aberrantly Expressed Timeless Regulates Cell Proliferation and Cisplatin Efficacy in Cervical Cancer. Hum Gene Ther 2020; 31(5-6):385-395.
- Deivendran S, Marzook KH, Radhakrishna Pillai M. The role of inflammation in cervical cancer. Adv Exp Med Biol 2014; 816: 377-399.
- Fan Y, Nan Y, Huang J, Zhong H, Zhou W. Up-regulation of inflammation-related LncRNA-IL7R predicts poor clinical outcome in patients with cervical cancer. Biosci Rep 2018; 38(3): BSR20180483.
- Hemmat N, Bannazadeh Baghi H. Association of human papillomavirus infection and inflammation in cervical cancer. Pathog Dis 2019; 77(5): ftz048. doi: 10.1093/femspd/ftz048..
- He A, Shao J, Zhang Y, Lu H, Wu Z, Xu Y. CD200Fc reduces LPS-induced IL-1beta activation in human cervical cancer cells by modulating TLR4-NF-kappaB and NLRP3 inflammasome pathway. Oncotarget. 2017; 8(20): 33214-33224.
- Zhu SL, Wu QH, Tu J. [Study on regulation of NLRP3/SOCS3-TLR4-NF-kappaB inflammatory pathway by wogonoside to improve hepatic insulin resistance]. Zhongguo Zhong Yao Za Zhi. 2019; 44(20): 4504-4510.
- Peng Y, Chen J, Dai Y, Jiang Y, Qiu W, Gu Y, Wang H. NLRP3 level in cerebrospinal fluid of patients with neuromyelitis optica spectrum disorders: Increased levels and association with disease severity. Mult Scler Relat Disord. 2019; 39: 101888.
- Li A, Yu Y, Ding X, Qin Y, Jiang Y, Wang X, Liu G, Chen X, Yue E, Sun X, Zahra SM, Yan Y, Ren L, Wang S, Chai L, Bai Y, Yang B. MiR-135b protects cardiomyocytes from infarction through restraining the NLRP3/caspase-1/IL-1beta pathway. Int J Cardiol 2020; 307:137-145.
- Cao R, Fang D, Wang J, Yu Y, Ye H, Kang P, Li Z, Wang H, Gao Q. ALDH2 Overexpression Alleviates High Glucose-Induced Cardiotoxicity by Inhibiting NLRP3 Inflammasome Activation. J Diabetes Res 2019; 2019: 4857921.
- Wang YZ, Wang AN, Gao XS, Du Y, Li L, Zhao JJ. [Effect of the small needle knife through the Zusanli(ST 36) on behavior and hippocampal expression of NLRP3 and IL-1beta in myalgia comorbid depressed rats]. Zhongguo Gu Shang. 2019; 32(12): 1151-1155.
- Abdullaha M, Ali M, Kour D, Kumar A, Bharate SB. Discovery of benzo[cd]indol-2-one and benzylidene-thiazolidine-2,4-dione as new classes of NLRP3 inflammasome inhibitors via ER-beta structure based virtual screening. Bioorg Chem. 2019; 95: 103500.
- Zhang H, Finiguerra M, Dam HG, Huang Y, Xu D, Liu G, Lin SJJoEMB, Ecology. An improved method for achieving high-quality RNA for copepod transcriptomic studies. 2013; 446(6): 57-66.
- Chen Y, Tan S, Liu M, Li J. LncRNA TINCR is downregulated in diabetic cardiomyopathy and relates to cardiomyocyte apoptosis. Scand Cardiovasc J 2018; 52(6): 335-339.
- Li H, Li B, Zhu D, Xie H, Du C, Xia Y, Tang W. Downregulation of lncRNA MEG3 and miR-770-5p inhibit cell migration and proliferation in Hirschsprung's disease. Oncotarget. 2017; 8(41): 69722-69730.
- Xu C, Ping Y, Zhao H, Ning S, Xia P, Wang W, Wan L, Li J, Zhang L, Yu L, Xiao Y. LncNetP, a systematical lncRNA prioritization approach based on ceRNA and disease phenotype association assumptions. Oncotarget. 2017; 8(70): 114603-114612.
- Yin Q, Wu A, Liu M. Plasma Long Non-Coding RNA (lncRNA) GAS5 is a New Biomarker for Coronary Artery Disease. Med Sci Monit. 2017; 23: 6042-6048.
- Miao H, Wang N, Shi LX, Wang Z, Song WB. Overexpression of mircoRNA-137 inhibits cervical cancer cell invasion, migration and epithelial-mesenchymal transition by suppressing the TGF-beta/smad pathway via binding to GREM1. Cancer Cell Int 2019; 19: 147.
- Fang YY, Tan MR, Zhou J, Liang L, Liu XY, Zhao K, Bao EC. miR-214-3p inhibits epithelial-to-mesenchymal transition and metastasis of endometrial cancer cells by targeting TWIST1. Onco Targets Ther 2019; 12: 9449-9458.
- Yang C, Kim HS, Park SJ, Lee EJ, Kim SI, Song G, Lim W. Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6. Cancers (Basel). 2019; 11(12): 1917. doi: 10.3390/cancers11121917.
- Peng R, Cheng X, Zhang Y, Lu X, Hu Z. miR-214 down-regulates MKK3 and suppresses malignant phenotypes of cervical cancer cells. Gene 2020; 724: 144146.
- Liu B, Liu Q, Pan S, Huang Y, Qi Y, Li S, Xiao Y, Jia L. The HOTAIR/miR-214/ST6GAL1 crosstalk modulates colorectal cancer procession through mediating sialylated c-Met via JAK2/STAT3 cascade. J Exp Clin Cancer Res. 2019; 38(1): 455.
- Han LC, Wang H, Niu FL, Yan JY, Cai HF. Effect miR-214-3p on proliferation and apoptosis of breast cancer cells by targeting survivin protein. Eur Rev Med Pharmacol Sci 2019; 23(17): 7469-7474.
- Sen P, Ghosal S, Hazra R, Arega S, Mohanty R, Kulkarni KK, Budhwar R, Ganguly N. Transcriptomic analyses of gene expression by CRISPR knockout of miR-214 in cervical cancer cells. Genomics 2020; 112(2): 1490-1499.
- Kuriakose T, Kanneganti TD. Pyroptosis in Antiviral Immunity. Curr Top Microbiol Immunol. 2019. doi: 10.1007/82_2019_189.
- Guo M, Yan R, Yao H, Duan L, Sun M, Xue Z, Jia Y. IFN Regulatory Factor 1 Mediates Macrophage Pyroptosis Induced by Oxidized Low-Density Lipoprotein in Patients with Acute Coronary Syndrome. Mediators Inflamm 2019; 2917128. doi: 10.1155/2019/2917128.
- Malireddi RKS, Gurung P, Kesavardhana S, Samir P, Burton A, Mummareddy H, Vogel P, Pelletier S, Burgula S, Kanneganti TD. Innate immune priming in the absence of TAK1 drives RIPK1 kinase activity-independent pyroptosis, apoptosis, necroptosis, and inflammatory disease. J Exp Med 2020; 217(3).
- Kahrizi D, Ghari SM, Ghaheri M, Fallah F, Ghorbani T, Beheshti AA, Kazemi E, Ansarypour Z. Effect of KH2PO4 on gene expression, morphological and biochemical characteristics of stevia rebaudiana Bertoni under in vitro conditions. Cell Mol Biol 63(7): 107-111.
- Ghaheri M, Kahrizi D, Bahrami G, Mohammadi-Motlagh HR. Study of gene expression and steviol glycosides accumulation in Stevia rebaudiana Bertoni under various mannitol concentrations. Mol Biol Rep 2019; 46(1): 7-16.
- Eruygur N, Ucar E, Akpulat HA, Shahsavari K, Safavi SM, Kahrizi D. In vitro antioxidant assessment, screening of enzyme inhibitory activities of methanol and water extracts and gene expression in Hypericum lydium. Mol Biol Rep 2019; 46(2): 2121-9.
- Esmaeili F, Ghaheri M, Kahrizi D, Mansouri M, Safavi SM, Ghorbani T, Muhammadi S, Rahmanian E, Vaziri S. Effects of various glutamine concentrations on gene expression and steviol glycosides accumulation in Stevia rebaudiana Bertoni. Cell Mol Biol, 64(2): 1-5.
- Akbari F, Arminian A, Kahrizi D, Fazeli A, Ghaheri M. Effect of nitrogen sources on gene expression of Stevia rebaudiana (Bertoni) under in vitro conditions. Cell Mol Biol, 64(2): 11-16.
- Akbarabadi A, Ismaili A, Kahrizi D, Firouzabadi FN. Validation of expression stability of reference genes in response to herbicide stress in wild oat (Avena ludoviciana). Cell Mol Biol 2018; 64(4). 113-118.
- Ghorbani T, Kahrizi D, Saeidi M, Arji I. Effect of sucrose concentrations on Stevia rebaudiana Bertoni tissue culture and gene expression. Cell Mol Biol, 63(11): 32-36.
- Ghaheri M, Adibrad E, Safavi SM, Kahrizi D, Soroush A, Muhammadi S, Ghorbani T, Sabzevari A, Ansarypour Z, Rahmanian E. Effects of life cycle and leaves location on gene expression and glycoside biosynthesis pathway in Stevia rebaudiana Bertoni. Cell Mol Biol, 64(2): 17-22.
- Kahrizi D, Ghaheri M, Yari Z, Yari K, Bahraminejad S. Investigation of different concentrations of MS media effects on gene expression and steviol glycosides accumulation in Stevia rebaudiana Bertoni. Cell Mol Biol, 64(2): 23-27.
- Hashempoor S, Ghaheri M, Kahrizi D, Kazemi N, Muhammadi S, Safavi SM, Ghorbani T, Rahmanian E, Heshmatpanaah M. Effects of different concentrations of mannitol on gene expression in Stevia rebaudiana Bertoni. Cell Mol Biol 64(2): 28-31.
- Fallah F, Nokhasi F, Ghaheri M, Kahrizi D, Beheshti Ale AA, Ghorbani T, Kazemi E, Ansarypour Z. Effect of salinity on gene expression, morphological and biochemical characteristics of Stevia rebaudiana Bertoni under in vitro conditions. Cell Mol Biol 2017; 63(7): 102-106.
- Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Mod Genet J 2020; 15(2): 75-92.
References
Hsieh VC, Chen ZJ, Liu CC, Chiang JH, Shieh SH, Hsieh MS. Forgone Health and Economic Benefits Associated with Socioeconomic Differences in Organized Cervical Cancer Screening. Asian Pac J Cancer Prev 2019; 20(12): 3755-3762.
Kaur G, Balasubramaniam SD, Lee YJ. IGFBP-2 in cervical cancer development. Exp Mol Pathol. 2019: 104362.
Zhang S, Wang W, Wu X, Liu W, Ding F. miR-16-5p modulates the radiosensitivity of cervical cancer cells via regulating coactivator-associated arginine methyltransferase 1. Pathol Int 2020; 70(1): 12-20.
Wang YY, Wang ZJ, Zhang Y, Gao XH, Yang CX, Zhao FH, Qiao YL, Ma L, Lang JH. [Economic evaluation of fifteen cervical cancer screening strategies in rural China]. Zhonghua Fu Chan Ke Za Zhi. 2019; 54(12): 840-847.
Zhou J, Zhang Y, Zou X, Kuai L, Wang L, Wang J, Shen F, Hu J, Zhang X, Huang Y, Chen Y. Aberrantly Expressed Timeless Regulates Cell Proliferation and Cisplatin Efficacy in Cervical Cancer. Hum Gene Ther 2020; 31(5-6):385-395.
Deivendran S, Marzook KH, Radhakrishna Pillai M. The role of inflammation in cervical cancer. Adv Exp Med Biol 2014; 816: 377-399.
Fan Y, Nan Y, Huang J, Zhong H, Zhou W. Up-regulation of inflammation-related LncRNA-IL7R predicts poor clinical outcome in patients with cervical cancer. Biosci Rep 2018; 38(3): BSR20180483.
Hemmat N, Bannazadeh Baghi H. Association of human papillomavirus infection and inflammation in cervical cancer. Pathog Dis 2019; 77(5): ftz048. doi: 10.1093/femspd/ftz048..
He A, Shao J, Zhang Y, Lu H, Wu Z, Xu Y. CD200Fc reduces LPS-induced IL-1beta activation in human cervical cancer cells by modulating TLR4-NF-kappaB and NLRP3 inflammasome pathway. Oncotarget. 2017; 8(20): 33214-33224.
Zhu SL, Wu QH, Tu J. [Study on regulation of NLRP3/SOCS3-TLR4-NF-kappaB inflammatory pathway by wogonoside to improve hepatic insulin resistance]. Zhongguo Zhong Yao Za Zhi. 2019; 44(20): 4504-4510.
Peng Y, Chen J, Dai Y, Jiang Y, Qiu W, Gu Y, Wang H. NLRP3 level in cerebrospinal fluid of patients with neuromyelitis optica spectrum disorders: Increased levels and association with disease severity. Mult Scler Relat Disord. 2019; 39: 101888.
Li A, Yu Y, Ding X, Qin Y, Jiang Y, Wang X, Liu G, Chen X, Yue E, Sun X, Zahra SM, Yan Y, Ren L, Wang S, Chai L, Bai Y, Yang B. MiR-135b protects cardiomyocytes from infarction through restraining the NLRP3/caspase-1/IL-1beta pathway. Int J Cardiol 2020; 307:137-145.
Cao R, Fang D, Wang J, Yu Y, Ye H, Kang P, Li Z, Wang H, Gao Q. ALDH2 Overexpression Alleviates High Glucose-Induced Cardiotoxicity by Inhibiting NLRP3 Inflammasome Activation. J Diabetes Res 2019; 2019: 4857921.
Wang YZ, Wang AN, Gao XS, Du Y, Li L, Zhao JJ. [Effect of the small needle knife through the Zusanli(ST 36) on behavior and hippocampal expression of NLRP3 and IL-1beta in myalgia comorbid depressed rats]. Zhongguo Gu Shang. 2019; 32(12): 1151-1155.
Abdullaha M, Ali M, Kour D, Kumar A, Bharate SB. Discovery of benzo[cd]indol-2-one and benzylidene-thiazolidine-2,4-dione as new classes of NLRP3 inflammasome inhibitors via ER-beta structure based virtual screening. Bioorg Chem. 2019; 95: 103500.
Zhang H, Finiguerra M, Dam HG, Huang Y, Xu D, Liu G, Lin SJJoEMB, Ecology. An improved method for achieving high-quality RNA for copepod transcriptomic studies. 2013; 446(6): 57-66.
Chen Y, Tan S, Liu M, Li J. LncRNA TINCR is downregulated in diabetic cardiomyopathy and relates to cardiomyocyte apoptosis. Scand Cardiovasc J 2018; 52(6): 335-339.
Li H, Li B, Zhu D, Xie H, Du C, Xia Y, Tang W. Downregulation of lncRNA MEG3 and miR-770-5p inhibit cell migration and proliferation in Hirschsprung's disease. Oncotarget. 2017; 8(41): 69722-69730.
Xu C, Ping Y, Zhao H, Ning S, Xia P, Wang W, Wan L, Li J, Zhang L, Yu L, Xiao Y. LncNetP, a systematical lncRNA prioritization approach based on ceRNA and disease phenotype association assumptions. Oncotarget. 2017; 8(70): 114603-114612.
Yin Q, Wu A, Liu M. Plasma Long Non-Coding RNA (lncRNA) GAS5 is a New Biomarker for Coronary Artery Disease. Med Sci Monit. 2017; 23: 6042-6048.
Miao H, Wang N, Shi LX, Wang Z, Song WB. Overexpression of mircoRNA-137 inhibits cervical cancer cell invasion, migration and epithelial-mesenchymal transition by suppressing the TGF-beta/smad pathway via binding to GREM1. Cancer Cell Int 2019; 19: 147.
Fang YY, Tan MR, Zhou J, Liang L, Liu XY, Zhao K, Bao EC. miR-214-3p inhibits epithelial-to-mesenchymal transition and metastasis of endometrial cancer cells by targeting TWIST1. Onco Targets Ther 2019; 12: 9449-9458.
Yang C, Kim HS, Park SJ, Lee EJ, Kim SI, Song G, Lim W. Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6. Cancers (Basel). 2019; 11(12): 1917. doi: 10.3390/cancers11121917.
Peng R, Cheng X, Zhang Y, Lu X, Hu Z. miR-214 down-regulates MKK3 and suppresses malignant phenotypes of cervical cancer cells. Gene 2020; 724: 144146.
Liu B, Liu Q, Pan S, Huang Y, Qi Y, Li S, Xiao Y, Jia L. The HOTAIR/miR-214/ST6GAL1 crosstalk modulates colorectal cancer procession through mediating sialylated c-Met via JAK2/STAT3 cascade. J Exp Clin Cancer Res. 2019; 38(1): 455.
Han LC, Wang H, Niu FL, Yan JY, Cai HF. Effect miR-214-3p on proliferation and apoptosis of breast cancer cells by targeting survivin protein. Eur Rev Med Pharmacol Sci 2019; 23(17): 7469-7474.
Sen P, Ghosal S, Hazra R, Arega S, Mohanty R, Kulkarni KK, Budhwar R, Ganguly N. Transcriptomic analyses of gene expression by CRISPR knockout of miR-214 in cervical cancer cells. Genomics 2020; 112(2): 1490-1499.
Kuriakose T, Kanneganti TD. Pyroptosis in Antiviral Immunity. Curr Top Microbiol Immunol. 2019. doi: 10.1007/82_2019_189.
Guo M, Yan R, Yao H, Duan L, Sun M, Xue Z, Jia Y. IFN Regulatory Factor 1 Mediates Macrophage Pyroptosis Induced by Oxidized Low-Density Lipoprotein in Patients with Acute Coronary Syndrome. Mediators Inflamm 2019; 2917128. doi: 10.1155/2019/2917128.
Malireddi RKS, Gurung P, Kesavardhana S, Samir P, Burton A, Mummareddy H, Vogel P, Pelletier S, Burgula S, Kanneganti TD. Innate immune priming in the absence of TAK1 drives RIPK1 kinase activity-independent pyroptosis, apoptosis, necroptosis, and inflammatory disease. J Exp Med 2020; 217(3).
Kahrizi D, Ghari SM, Ghaheri M, Fallah F, Ghorbani T, Beheshti AA, Kazemi E, Ansarypour Z. Effect of KH2PO4 on gene expression, morphological and biochemical characteristics of stevia rebaudiana Bertoni under in vitro conditions. Cell Mol Biol 63(7): 107-111.
Ghaheri M, Kahrizi D, Bahrami G, Mohammadi-Motlagh HR. Study of gene expression and steviol glycosides accumulation in Stevia rebaudiana Bertoni under various mannitol concentrations. Mol Biol Rep 2019; 46(1): 7-16.
Eruygur N, Ucar E, Akpulat HA, Shahsavari K, Safavi SM, Kahrizi D. In vitro antioxidant assessment, screening of enzyme inhibitory activities of methanol and water extracts and gene expression in Hypericum lydium. Mol Biol Rep 2019; 46(2): 2121-9.
Esmaeili F, Ghaheri M, Kahrizi D, Mansouri M, Safavi SM, Ghorbani T, Muhammadi S, Rahmanian E, Vaziri S. Effects of various glutamine concentrations on gene expression and steviol glycosides accumulation in Stevia rebaudiana Bertoni. Cell Mol Biol, 64(2): 1-5.
Akbari F, Arminian A, Kahrizi D, Fazeli A, Ghaheri M. Effect of nitrogen sources on gene expression of Stevia rebaudiana (Bertoni) under in vitro conditions. Cell Mol Biol, 64(2): 11-16.
Akbarabadi A, Ismaili A, Kahrizi D, Firouzabadi FN. Validation of expression stability of reference genes in response to herbicide stress in wild oat (Avena ludoviciana). Cell Mol Biol 2018; 64(4). 113-118.
Ghorbani T, Kahrizi D, Saeidi M, Arji I. Effect of sucrose concentrations on Stevia rebaudiana Bertoni tissue culture and gene expression. Cell Mol Biol, 63(11): 32-36.
Ghaheri M, Adibrad E, Safavi SM, Kahrizi D, Soroush A, Muhammadi S, Ghorbani T, Sabzevari A, Ansarypour Z, Rahmanian E. Effects of life cycle and leaves location on gene expression and glycoside biosynthesis pathway in Stevia rebaudiana Bertoni. Cell Mol Biol, 64(2): 17-22.
Kahrizi D, Ghaheri M, Yari Z, Yari K, Bahraminejad S. Investigation of different concentrations of MS media effects on gene expression and steviol glycosides accumulation in Stevia rebaudiana Bertoni. Cell Mol Biol, 64(2): 23-27.
Hashempoor S, Ghaheri M, Kahrizi D, Kazemi N, Muhammadi S, Safavi SM, Ghorbani T, Rahmanian E, Heshmatpanaah M. Effects of different concentrations of mannitol on gene expression in Stevia rebaudiana Bertoni. Cell Mol Biol 64(2): 28-31.
Fallah F, Nokhasi F, Ghaheri M, Kahrizi D, Beheshti Ale AA, Ghorbani T, Kazemi E, Ansarypour Z. Effect of salinity on gene expression, morphological and biochemical characteristics of Stevia rebaudiana Bertoni under in vitro conditions. Cell Mol Biol 2017; 63(7): 102-106.
Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Mod Genet J 2020; 15(2): 75-92.