Issue
Long noncoding RNA H19 promotes vincristine resistance in multiple myeloma by targeting Akt
Corresponding Author(s) : Shijuan Xu
Cellular and Molecular Biology,
Vol. 66 No. 6: Issue 6
Abstract
Multiple myeloma is a malignant proliferation of plasma cells that results from a single clone. Manifestations include bone pain or fractures, kidney failure, susceptibility to infection, anemia, and hypercalcemia. To investigate the relationship between vincristine (VCR) resistance and Long noncoding RNA H19 (Lnc-RNA H19) in multiple myeloma (MM) this experiment was set up. For this aim, RT-PCR was used to detect the expression of lnc-RNA H19 in 60 MM patients from No.215 Hospital of Shaanxi Nuclear Industry and 50 healthy controls, and further detected the expression of related genes in myeloma cell lines and VCR myeloma resistant strains. MTT assay, flow cytometry assay, western-blotting assay and luciferase assay were used to analyze the growth, apoptosis and protein phosphorylation levels of drug-resistant RPMI 8226/VCR and RPMI 8226 cells after VCR treatment and plasmid transprinting. Results showed that the relative expression of lnc-RNA H19 was significantly increased in MM patients and drug-resistant strains RPMI 8226-VCR (****p<0.0001), while apoptosis of various MM cell lines increased after VCR treatment, while apoptosis of RPMI 8226-VCR was significantly decreased (***p<0.001). Lnc-RNA H19 overexpression plasmid pcdna3.1-h19 and Akt overexpression plasmid pcdna3.1-akt decreased apoptosis in RPMI 8226 cell lines without VCR resistance (***p<0.001), while the recombination of siRNA-h19 and siRNA-akt plasmid increased apoptosis in RPMI 8226-VCR (***p<0.001). The lnc-RNA H19/Akt pathway is closely related to the occurrence of VCR resistance in MM cells, and the down-regulation of H19 can significantly improve the sensitivity of VCR in MM.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- Manier S, Liu CJ, Avet-Loiseau H, Park J, Shi J, Campigotto F, Salem KZ, Huynh D, Glavey SV, Rivotto B, Sacco A. Prognostic role of circulating exosomal miRNAs in multiple myeloma. Blood, J Am Society Hematol 2017; 129(17):2429-36.
- Kumar SK, Rajkumar V, Kyle RA, van Duin M, Sonneveld P, Mateos MV, Gay F, Anderson KC. Multiple myeloma. Nat Rev Dis Primers 2017; 3(1):1-20.
- Robiou-Du-Pont S, Cleynen A, Fontan C, Attal M, Munshi N, Corre J, Avet-Loiseau H. Genom Mult Myeloma. 2018; 35(9):963-967.
- Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ, Weiss BM, Krishnan A, Lentzsch S, Comenzo R, Wang J. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood, J Am Society Hematol 2017; 130(8):974-81.
- Raje N, Terpos E, Willenbacher W, Shimizu K, García-Sanz R, Durie B, Legieć W, Krejćí M, Laribi K, Zhu L, Cheng P. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol 2018; 19(3):370-81.
- Gay F, Engelhardt M, Terpos E, Wäsch R, Giaccone L, Auner HW, Caers J, Gramatzki M, Van De Donk N, Oliva S, Zamagni E. From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives. Haematol 2018; 103(2):197-211.
- Zhang L, Zhou Y, Huang T, Cheng AS, Yu J, Kang W, To KF. The interplay of LncRNA-H19 and its binding partners in physiological process and gastric carcinogenesis. Int J Mol Sci 2017; 18(2):450.
- Tao SC, Rui BY, Wang QY, Zhou D, Zhang Y, Guo SC. Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing endogenous RNA for the treatment of diabetic wounds. Drug Deliv 2018; 25(1):241-55.
- Peng F, Li TT, Wang KL, Xiao GQ, Wang JH, Zhao HD, Kang ZJ, Fan WJ, Zhu LL, Li M, Cui B. H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance. Cell Death Dis 2018; 8(1):e2569-.
- Lv M, Zhong Z, Huang M, Tian Q, Jiang R, Chen J. lncRNA H19 regulates epithelial–mesenchymal transition and metastasis of bladder cancer by miR-29b-3p as competing endogenous RNA. Biochim Biophys Acta Mol Cell Res 2017; 1864(10):1887-99.
- Jia L, Tian Y, Chen Y, Zhang G. The silencing of LncRNA-H19 decreases chemoresistance of human glioma cells to temozolomide by suppressing epithelial-mesenchymal transition via the Wnt/β-Catenin pathway. Onco Targets Ther 2018; 11:313.
- Zhang Z, Gao W, Long QQ, Zhang J, Li YF, Yan JJ, Yang ZJ, Wang LS. Increased plasma levels of lncRNA H19 and LIPCAR are associated with increased risk of coronary artery disease in a Chinese population. Sci Rep 2017; 7(1):1-9.
- Li XF, Yin XH, Cai JW, Wang MJ, Zeng YQ, Li M, Niu YM, Shen M. Significant association between lncRNA H19 polymorphisms and cancer susceptibility: a meta-analysis. Oncotarget 2017; 8(28):45143.
- Wang P, Xu J, Wang Y, Cao X. An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism. Sci 2017; 358(6366):1051-5.
- Liu X, Zhang L, Cui J, Che S, Liu Y, Zhang Y, Cao B, Song Y. The mRNA and lncRNA landscape of the non-pregnant endometrium during the oestrus cycle in dairy goat. Anim Prod Sci 2019; 59(10):1803-13.
- Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 2012; 22(9):1775-89.
- Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, Zhu N, Zhou WP, Yang GS, Wang YZ, Shang JL. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatol 2011; 54(5):1679-89.
- Klattenhoff CA, Scheuermann JC, Surface LE, Bradley RK, Fields PA, Steinhauser ML, Ding H, Butty VL, Torrey L, Haas S, Abo R. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell 2013; 152(3):570-83.
- Grote P, Wittler L, Hendrix D, Koch F, Währisch S, Beisaw A, Macura K, Bläss G, Kellis M, Werber M, Herrmann BG. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell 2013; 24(2):206-14.
- Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell 2011; 43(6):904-14.
- O'Donnell JS, Massi D, Teng MW, Mandala M. PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux. Semin Cancer Biol 2018; (Vol. 48, pp. 91-103). Academic Press.
- Costa RL, Han HS, Gradishar WJ. Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review. Breast Cancer Res Treat 2018; 169(3):397-406.
- Wei L, Chen Q, Guo A, Fan J, Wang R, Zhang H. Asiatic acid attenuates CCl4-induced liver fibrosis in rats by regulating the PI3K/AKT/mTOR and Bcl-2/Bax signaling pathways. Int Immunopharmacol 2018; 60:1-8..
- He L, Wang X, Kang N, Xu J, Dai N, Xu X, Zhang H. MiR-375 inhibits the hepatocyte growth factor-elicited migration of mesenchymal stem cells by downregulating Akt signaling. Cell Tissue Res 2018; 372(1):99-114.
- Chakraborty A, Koldobskiy MA, Bello NT, Maxwell M, Potter JJ, Juluri KR, Maag D, Kim S, Huang AS, Dailey MJ, Saleh M. Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell 2010;143(6):897-910.
- Singh A, Permar V, Basavaraj, Tomar BS, Praveen S. Effect of temperature on symptoms expression and viral RNA accumulation in groundnut bud necrosis virus infected Vigna unguiculata. Iran J Biotechnol. 2018; 16(3): e1846.
- Behdani E, Ghaderi-Zefrehei M, Rafeie F, Bakhtiarizadeh MR, Roshanfeker H, Fayazi J. RNA-Seq Bayesian Network Exploration of Immune System in Bovine. Iran J Biotechnol. 2019; 17(3): e1748.
- Hajieghrari B, Farrokhi N, Goliaei B, Kavousi K. Computational Identification of MicroRNAs and Their Transcript Target(s) in Field Mustard (Brassica rapa L.). Iran J Biotechnol. 2017; 15(1): 22-32.
- Mandal UR, Das SS, Chattopadhyay B, Sahoo S. Identified Hybrid tRNA Structure Genes in Archaeal Genome. Iran J Biotechnol. 2019; 17(3): e2254.
- Singh A, Permar V, Basavaraj, Tomar BS, Praveen S. Effect of Temperature on Symptoms Expression and Viral RNA Accumulation in Groundnut Bud Necrosis Virus Infected Vigna unguiculata. Iran J Biotechnol. 2018; 16(3): e1846.
- 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.
- Posey JE, Walz K. Introduction to Human Genetics. In Cellular and Animal Models in Human Genomics Research 2019 Jan 1 (pp. 1-17). Academic Press.
- Burgess S, Foley CN, Zuber V. Inferring Causal Relationships between Risk Factors and Outcomes Using Genetic Variation. Handbook of Statistical Genomics: Two Volume Set. 2019; 29: 651-20.
References
Manier S, Liu CJ, Avet-Loiseau H, Park J, Shi J, Campigotto F, Salem KZ, Huynh D, Glavey SV, Rivotto B, Sacco A. Prognostic role of circulating exosomal miRNAs in multiple myeloma. Blood, J Am Society Hematol 2017; 129(17):2429-36.
Kumar SK, Rajkumar V, Kyle RA, van Duin M, Sonneveld P, Mateos MV, Gay F, Anderson KC. Multiple myeloma. Nat Rev Dis Primers 2017; 3(1):1-20.
Robiou-Du-Pont S, Cleynen A, Fontan C, Attal M, Munshi N, Corre J, Avet-Loiseau H. Genom Mult Myeloma. 2018; 35(9):963-967.
Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ, Weiss BM, Krishnan A, Lentzsch S, Comenzo R, Wang J. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood, J Am Society Hematol 2017; 130(8):974-81.
Raje N, Terpos E, Willenbacher W, Shimizu K, García-Sanz R, Durie B, Legieć W, Krejćí M, Laribi K, Zhu L, Cheng P. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol 2018; 19(3):370-81.
Gay F, Engelhardt M, Terpos E, Wäsch R, Giaccone L, Auner HW, Caers J, Gramatzki M, Van De Donk N, Oliva S, Zamagni E. From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives. Haematol 2018; 103(2):197-211.
Zhang L, Zhou Y, Huang T, Cheng AS, Yu J, Kang W, To KF. The interplay of LncRNA-H19 and its binding partners in physiological process and gastric carcinogenesis. Int J Mol Sci 2017; 18(2):450.
Tao SC, Rui BY, Wang QY, Zhou D, Zhang Y, Guo SC. Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing endogenous RNA for the treatment of diabetic wounds. Drug Deliv 2018; 25(1):241-55.
Peng F, Li TT, Wang KL, Xiao GQ, Wang JH, Zhao HD, Kang ZJ, Fan WJ, Zhu LL, Li M, Cui B. H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance. Cell Death Dis 2018; 8(1):e2569-.
Lv M, Zhong Z, Huang M, Tian Q, Jiang R, Chen J. lncRNA H19 regulates epithelial–mesenchymal transition and metastasis of bladder cancer by miR-29b-3p as competing endogenous RNA. Biochim Biophys Acta Mol Cell Res 2017; 1864(10):1887-99.
Jia L, Tian Y, Chen Y, Zhang G. The silencing of LncRNA-H19 decreases chemoresistance of human glioma cells to temozolomide by suppressing epithelial-mesenchymal transition via the Wnt/β-Catenin pathway. Onco Targets Ther 2018; 11:313.
Zhang Z, Gao W, Long QQ, Zhang J, Li YF, Yan JJ, Yang ZJ, Wang LS. Increased plasma levels of lncRNA H19 and LIPCAR are associated with increased risk of coronary artery disease in a Chinese population. Sci Rep 2017; 7(1):1-9.
Li XF, Yin XH, Cai JW, Wang MJ, Zeng YQ, Li M, Niu YM, Shen M. Significant association between lncRNA H19 polymorphisms and cancer susceptibility: a meta-analysis. Oncotarget 2017; 8(28):45143.
Wang P, Xu J, Wang Y, Cao X. An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism. Sci 2017; 358(6366):1051-5.
Liu X, Zhang L, Cui J, Che S, Liu Y, Zhang Y, Cao B, Song Y. The mRNA and lncRNA landscape of the non-pregnant endometrium during the oestrus cycle in dairy goat. Anim Prod Sci 2019; 59(10):1803-13.
Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 2012; 22(9):1775-89.
Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, Zhu N, Zhou WP, Yang GS, Wang YZ, Shang JL. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatol 2011; 54(5):1679-89.
Klattenhoff CA, Scheuermann JC, Surface LE, Bradley RK, Fields PA, Steinhauser ML, Ding H, Butty VL, Torrey L, Haas S, Abo R. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell 2013; 152(3):570-83.
Grote P, Wittler L, Hendrix D, Koch F, Währisch S, Beisaw A, Macura K, Bläss G, Kellis M, Werber M, Herrmann BG. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell 2013; 24(2):206-14.
Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell 2011; 43(6):904-14.
O'Donnell JS, Massi D, Teng MW, Mandala M. PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux. Semin Cancer Biol 2018; (Vol. 48, pp. 91-103). Academic Press.
Costa RL, Han HS, Gradishar WJ. Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review. Breast Cancer Res Treat 2018; 169(3):397-406.
Wei L, Chen Q, Guo A, Fan J, Wang R, Zhang H. Asiatic acid attenuates CCl4-induced liver fibrosis in rats by regulating the PI3K/AKT/mTOR and Bcl-2/Bax signaling pathways. Int Immunopharmacol 2018; 60:1-8..
He L, Wang X, Kang N, Xu J, Dai N, Xu X, Zhang H. MiR-375 inhibits the hepatocyte growth factor-elicited migration of mesenchymal stem cells by downregulating Akt signaling. Cell Tissue Res 2018; 372(1):99-114.
Chakraborty A, Koldobskiy MA, Bello NT, Maxwell M, Potter JJ, Juluri KR, Maag D, Kim S, Huang AS, Dailey MJ, Saleh M. Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell 2010;143(6):897-910.
Singh A, Permar V, Basavaraj, Tomar BS, Praveen S. Effect of temperature on symptoms expression and viral RNA accumulation in groundnut bud necrosis virus infected Vigna unguiculata. Iran J Biotechnol. 2018; 16(3): e1846.
Behdani E, Ghaderi-Zefrehei M, Rafeie F, Bakhtiarizadeh MR, Roshanfeker H, Fayazi J. RNA-Seq Bayesian Network Exploration of Immune System in Bovine. Iran J Biotechnol. 2019; 17(3): e1748.
Hajieghrari B, Farrokhi N, Goliaei B, Kavousi K. Computational Identification of MicroRNAs and Their Transcript Target(s) in Field Mustard (Brassica rapa L.). Iran J Biotechnol. 2017; 15(1): 22-32.
Mandal UR, Das SS, Chattopadhyay B, Sahoo S. Identified Hybrid tRNA Structure Genes in Archaeal Genome. Iran J Biotechnol. 2019; 17(3): e2254.
Singh A, Permar V, Basavaraj, Tomar BS, Praveen S. Effect of Temperature on Symptoms Expression and Viral RNA Accumulation in Groundnut Bud Necrosis Virus Infected Vigna unguiculata. Iran J Biotechnol. 2018; 16(3): e1846.
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.
Posey JE, Walz K. Introduction to Human Genetics. In Cellular and Animal Models in Human Genomics Research 2019 Jan 1 (pp. 1-17). Academic Press.
Burgess S, Foley CN, Zuber V. Inferring Causal Relationships between Risk Factors and Outcomes Using Genetic Variation. Handbook of Statistical Genomics: Two Volume Set. 2019; 29: 651-20.