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Published in: Pathology & Oncology Research 4/2013

01-10-2013 | Research

miR-135a/b Modulate Cisplatin Resistance of Human Lung Cancer Cell Line by Targeting MCL1

Authors: Li Zhou, Tianzhu Qiu, Jing Xu, Tongshan Wang, Jian Wang, Xin Zhou, Zebo Huang, Wei Zhu, Yongqian Shu, Ping Liu

Published in: Pathology & Oncology Research | Issue 4/2013

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Abstract

microRNAs (miRNAs) are short non-coding RNA molecules, which post-transcriptionally regulate genes expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. Here, we investigated the possible role of miRNAs in the development of drug resistance in human lung cancer cell line. We found that miR-135a/b were downregulated while MCL1 was upregulated in A549/CDDP (cisplatin) cells, compared with the parental A549 cells. In vitro drug sensitivity assay demonstrated that overexpression of miR-135a/b sensitized A549/CDDP cells to cisplatin. The luciferase activity of MCL1 3′-untranslated region-based reporter constructed in A549/CDDP cells suggested that MCL1 was the direct target gene of miR-135a/b. Enforced miR-135a/b expression reduced MCL1 protein level and sensitized A549/CDDP cells to CDDP-induced apoptosis. Taken together, our findings first suggested that hsa-miR-135a/b could play a role in the development of CDDP resistance in lung cancer cell line at least in part by modulation of apoptosis via targeting MCL1.
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Literature
1.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–917PubMedCrossRef Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–917PubMedCrossRef
2.
go back to reference Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM (2006) Targeting multidrug resistance in cancer. Nat Rev Drug Disc 5:219–34CrossRef Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM (2006) Targeting multidrug resistance in cancer. Nat Rev Drug Disc 5:219–34CrossRef
3.
go back to reference Rabik CA, Dolan ME (2007) Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev 33:9–23PubMedCrossRef Rabik CA, Dolan ME (2007) Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev 33:9–23PubMedCrossRef
4.
go back to reference Johnstone RW, Ruefli AA, Lowe SW (2002) Apoptosis: A link between cancer genetics and chemotherapy. Cell 108:153–64PubMedCrossRef Johnstone RW, Ruefli AA, Lowe SW (2002) Apoptosis: A link between cancer genetics and chemotherapy. Cell 108:153–64PubMedCrossRef
5.
go back to reference Zhang K, Mack P, Wong KP (1998) Glutathione-related mechanisms in cellular resistance to anticancer drugs. Int J Oncol 12:871–82PubMed Zhang K, Mack P, Wong KP (1998) Glutathione-related mechanisms in cellular resistance to anticancer drugs. Int J Oncol 12:871–82PubMed
6.
go back to reference Konopleva M, Tabe Y, Zeng Z, Andreeff M (2009) Therapeutic targeting of microenvironmental interactions in leukemia: Mechanisms and approaches. Drug Resist Updat 12:103–113PubMedCrossRef Konopleva M, Tabe Y, Zeng Z, Andreeff M (2009) Therapeutic targeting of microenvironmental interactions in leukemia: Mechanisms and approaches. Drug Resist Updat 12:103–113PubMedCrossRef
7.
go back to reference Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, Stassi G (2007) Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1:389–402PubMedCrossRef Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, Stassi G (2007) Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1:389–402PubMedCrossRef
8.
go back to reference Voulgari A, Pintzas A (2009) Epithelial-mesenchymal transition in cancer metastasis: Mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta 1796(2):75–90PubMed Voulgari A, Pintzas A (2009) Epithelial-mesenchymal transition in cancer metastasis: Mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta 1796(2):75–90PubMed
9.
go back to reference Wang B, Yang H, Huang YZ, Yan RH, Liu FJ, Zhang JN (2010) Biologic characteristics of the side population of human small cell lung cancer cell line H446. Chin J Cancer 29:254–60PubMedCrossRef Wang B, Yang H, Huang YZ, Yan RH, Liu FJ, Zhang JN (2010) Biologic characteristics of the side population of human small cell lung cancer cell line H446. Chin J Cancer 29:254–60PubMedCrossRef
10.
go back to reference Sarkar FH, Li Y, Wang Z, Kong D, Ali S (2010) Implication of microRNAs in drug resistance for designing novel cancer therapy. Drug Resist Updat 13:57–66PubMedCrossRef Sarkar FH, Li Y, Wang Z, Kong D, Ali S (2010) Implication of microRNAs in drug resistance for designing novel cancer therapy. Drug Resist Updat 13:57–66PubMedCrossRef
11.
12.
go back to reference Aigner A (2011) MicroRNAs (miRNAs) in cancer invasion and metastasis: Therapeutic approaches based on metastasis-related miRNAs. J Mol Med (Berl) 89:445–57CrossRef Aigner A (2011) MicroRNAs (miRNAs) in cancer invasion and metastasis: Therapeutic approaches based on metastasis-related miRNAs. J Mol Med (Berl) 89:445–57CrossRef
13.
go back to reference Rottiers V, Najafi-Shoushtari SH, Kristo F, Gurumurthy S, Zhong L, Li Y, Cohen DE, Gerszten RE, Bardeesy N, Mostoslavsky R, Näär AM (2011) MicroRNAs in metabolism and metabolic diseases. Cold Spring Harb Symp Quant Biol 76:225–33PubMedCrossRef Rottiers V, Najafi-Shoushtari SH, Kristo F, Gurumurthy S, Zhong L, Li Y, Cohen DE, Gerszten RE, Bardeesy N, Mostoslavsky R, Näär AM (2011) MicroRNAs in metabolism and metabolic diseases. Cold Spring Harb Symp Quant Biol 76:225–33PubMedCrossRef
14.
go back to reference Cho WC (2010) MicroRNAs: Potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol 42:1273–81PubMedCrossRef Cho WC (2010) MicroRNAs: Potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol 42:1273–81PubMedCrossRef
15.
16.
go back to reference Xu K, Liang X, Cui D, Wu Y, Shi W, Liu J (2011) miR-1915 inhibits Bcl-2 to modulate multidrug resistance by increasing drug-sensitivity in human colorectal carcinoma cells. Mol Carcinog. doi:10.1002/mc.21832 Xu K, Liang X, Cui D, Wu Y, Shi W, Liu J (2011) miR-1915 inhibits Bcl-2 to modulate multidrug resistance by increasing drug-sensitivity in human colorectal carcinoma cells. Mol Carcinog. doi:10.​1002/​mc.​21832
17.
go back to reference Li H, Hui L, Xu W (2012) miR-181a sensitizes a multidrug-resistant leukemia cell line K562/A02 to daunorubicin by targeting BCL-2. Acta Biochim Biophys Sin 44:269–77PubMedCrossRef Li H, Hui L, Xu W (2012) miR-181a sensitizes a multidrug-resistant leukemia cell line K562/A02 to daunorubicin by targeting BCL-2. Acta Biochim Biophys Sin 44:269–77PubMedCrossRef
18.
go back to reference Zhang S, Wan Y, Pan T, Gu X, Qian C, Sun G, Sun L, Xiang Y, Wang Z, Shi L (2012) MicroRNA-21 inhibitor sensitizes human glioblastoma U251 stem cells to chemotherapeutic drugTemozolomide. J Mol Neurosci 47:346–56PubMedCrossRef Zhang S, Wan Y, Pan T, Gu X, Qian C, Sun G, Sun L, Xiang Y, Wang Z, Shi L (2012) MicroRNA-21 inhibitor sensitizes human glioblastoma U251 stem cells to chemotherapeutic drugTemozolomide. J Mol Neurosci 47:346–56PubMedCrossRef
19.
go back to reference Ru P, Steele R, Hsueh EC, Ray RB (2011) Anti-miR-203 upregulates SOCS3 expression in breast cancer cells and enhances cisplatin chemosensitivity. Genes Cancer 2:720–7PubMedCrossRef Ru P, Steele R, Hsueh EC, Ray RB (2011) Anti-miR-203 upregulates SOCS3 expression in breast cancer cells and enhances cisplatin chemosensitivity. Genes Cancer 2:720–7PubMedCrossRef
20.
go back to reference Fu X, Tian J, Zhang L, Chen Y, Hao Q (2012) Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer cells. FEBS Lett 586:1279–86PubMedCrossRef Fu X, Tian J, Zhang L, Chen Y, Hao Q (2012) Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer cells. FEBS Lett 586:1279–86PubMedCrossRef
21.
go back to reference Zhu W, Zhu D, Lu S, Wang T, Wang J, Jiang B, Shu Y, Liu P (2012) miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2. Med Oncol 29:384–91PubMedCrossRef Zhu W, Zhu D, Lu S, Wang T, Wang J, Jiang B, Shu Y, Liu P (2012) miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2. Med Oncol 29:384–91PubMedCrossRef
22.
go back to reference 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 25:402–8PubMedCrossRef 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 25:402–8PubMedCrossRef
23.
go back to reference Yamaue H, Tanimura H, Noguchi K, Hotta T, Tani M, Tsunoda T, Iwahashi M, Tamai M, Iwakura S (1992) Chemosensitivity testing of fresh human gastric cancer with highly purified tumor cells using the MTT assay. Br J Cancer 66:794–9PubMedCrossRef Yamaue H, Tanimura H, Noguchi K, Hotta T, Tani M, Tsunoda T, Iwahashi M, Tamai M, Iwakura S (1992) Chemosensitivity testing of fresh human gastric cancer with highly purified tumor cells using the MTT assay. Br J Cancer 66:794–9PubMedCrossRef
24.
go back to reference Yamaue H, Tani M, Onishi H, Kinoshita H, Nakamori M, Yokoyama S, Iwahashi M, Uchiyama K (2002) Locoregional chemotherapy for patients with pancreatic cancer intraarterial adjuvant chemotherapy after pancreatectomy with portal vein resection. Pancreas 25:366–72PubMedCrossRef Yamaue H, Tani M, Onishi H, Kinoshita H, Nakamori M, Yokoyama S, Iwahashi M, Uchiyama K (2002) Locoregional chemotherapy for patients with pancreatic cancer intraarterial adjuvant chemotherapy after pancreatectomy with portal vein resection. Pancreas 25:366–72PubMedCrossRef
25.
go back to reference Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, Hong L, Liu J, Fan D (2008) miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer 123:372–9PubMedCrossRef Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, Hong L, Liu J, Fan D (2008) miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer 123:372–9PubMedCrossRef
26.
go back to reference Quinn BA, Dash R, Azab B, Sarkar S, Das SK, Kumar S, Oyesanya RA, Dasgupta S, Dent P, Grant S, Rahmani M, Curiel DT, Dmitriev I, Hedvat M, Wei J, Wu B, Stebbins JL, Reed JC, Pellecchia M, Sarkar D, Fisher PB (2011) Targeting Mcl-1 for the therapy of cancer. Expert Opin Investig Drugs 20:1397–411PubMedCrossRef Quinn BA, Dash R, Azab B, Sarkar S, Das SK, Kumar S, Oyesanya RA, Dasgupta S, Dent P, Grant S, Rahmani M, Curiel DT, Dmitriev I, Hedvat M, Wei J, Wu B, Stebbins JL, Reed JC, Pellecchia M, Sarkar D, Fisher PB (2011) Targeting Mcl-1 for the therapy of cancer. Expert Opin Investig Drugs 20:1397–411PubMedCrossRef
27.
go back to reference Wu S, Lin Y, Xu D, Chen J, Shu M, Zhou Y, Zhu W, Su X, Zhou Y, Qiu P, Yan G (2011) MiR-135a functions as a selective killer of malignant glioma. Oncogene. doi:10.1038/onc.2011.551 Wu S, Lin Y, Xu D, Chen J, Shu M, Zhou Y, Zhu W, Su X, Zhou Y, Qiu P, Yan G (2011) MiR-135a functions as a selective killer of malignant glioma. Oncogene. doi:10.​1038/​onc.​2011.​551
28.
go back to reference Navarro A, Diaz T, Martinez A, Gaya A, Pons A, Gel B, Codony C, Ferrer G, Martinez C, Montserrat E, Monzo M (2009) Regulation of JAK2 by miR-135a: Prognostic impact in classic Hodgkin lymphoma. Blood 114:2945–51PubMedCrossRef Navarro A, Diaz T, Martinez A, Gaya A, Pons A, Gel B, Codony C, Ferrer G, Martinez C, Montserrat E, Monzo M (2009) Regulation of JAK2 by miR-135a: Prognostic impact in classic Hodgkin lymphoma. Blood 114:2945–51PubMedCrossRef
29.
go back to reference Chen Y, Zhang J, Wang H, Zhao J, Xu C, Du Y, Luo X, Zheng F, Liu R, Zhang H, Ma D (2012) miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10. BMC Cancer 12:111PubMedCrossRef Chen Y, Zhang J, Wang H, Zhao J, Xu C, Du Y, Luo X, Zheng F, Liu R, Zhang H, Ma D (2012) miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10. BMC Cancer 12:111PubMedCrossRef
30.
go back to reference Matsuyama H, Suzuki HI, Nishimori H, Noguchi M, Yao T, Komatsu N, Mano H, Sugimoto K, Miyazono K (2011) miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. Blood 118:6881–92PubMedCrossRef Matsuyama H, Suzuki HI, Nishimori H, Noguchi M, Yao T, Komatsu N, Mano H, Sugimoto K, Miyazono K (2011) miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. Blood 118:6881–92PubMedCrossRef
31.
go back to reference Hummel R, Hussey DJ, Haier J (2010) MicroRNAs: Predictors and modifiers of chemo- and radiotherapy in different tumour types. Eur J Cancer 46:298–311PubMedCrossRef Hummel R, Hussey DJ, Haier J (2010) MicroRNAs: Predictors and modifiers of chemo- and radiotherapy in different tumour types. Eur J Cancer 46:298–311PubMedCrossRef
32.
go back to reference Pérez-Tomás R (2006) Multidrug resistance: Retrospect and prospects in anti-cancer drug treatment. Curr Med Chem 13:1859–76PubMedCrossRef Pérez-Tomás R (2006) Multidrug resistance: Retrospect and prospects in anti-cancer drug treatment. Curr Med Chem 13:1859–76PubMedCrossRef
33.
go back to reference Borowski E, Bontemps-Gracz MM, Piwkowska A (2005) Strategies for overcoming ABC-transporters-mediated multidrug resistance (MDR) of tumor cells. Acta Biochim Pol 52:609–27PubMed Borowski E, Bontemps-Gracz MM, Piwkowska A (2005) Strategies for overcoming ABC-transporters-mediated multidrug resistance (MDR) of tumor cells. Acta Biochim Pol 52:609–27PubMed
Metadata
Title
miR-135a/b Modulate Cisplatin Resistance of Human Lung Cancer Cell Line by Targeting MCL1
Authors
Li Zhou
Tianzhu Qiu
Jing Xu
Tongshan Wang
Jian Wang
Xin Zhou
Zebo Huang
Wei Zhu
Yongqian Shu
Ping Liu
Publication date
01-10-2013
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 4/2013
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-013-9630-4

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