Knockdown of HOXA10 reverses the multidrug resistance of human chronic mylogenous leukemia K562/ADM cells by downregulating P-gp and MRP-1 Corrigendum in /10.3892/ijmm.2023.5315

Yi,Ying-Jie; Jia,Xiu-Hong; Wang,Jian-Yong; Li,You-Jie; Wang,Hong; Xie,Shu-Yang

doi:10.3892/ijmm.2016.2539

Knockdown of HOXA10 reverses the multidrug resistance of human chronic mylogenous leukemia K562/ADM cells by downregulating P-gp and MRP-1

Corrigendum in: /10.3892/ijmm.2023.5315

Authors:
- Ying-Jie Yi
- Xiu-Hong Jia
- Jian-Yong Wang
- You-Jie Li
- Hong Wang
- Shu-Yang Xie
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Affiliations: Department of Pediatrics, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong 256603, P.R. China, Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai, Shangdong 264000, P.R. China, Department of Biochemistry and Molecular Biology, Key Laboratory of Tumour Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Published online on: March 24, 2016 https://doi.org/10.3892/ijmm.2016.2539
Pages: 1405-1411

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Abstract

Multidrug resistance (MDR) of leukemia cells is a major obstacle in chemotherapeutic treatment. The high expression and constitutive activation of P-glycoprotein (P-gp) and multidrug resistance protein-1 (MRP-1) have been reported to play a vital role in enhancing cell resistance to anticancer drugs in many tumors. The present study aimed to investigate the reversal of MDR by silencing homeobox A10 (HOXA10) in adriamycin (ADR)-resistant human chronic myelogenous leukemia (CML) K562/ADM cells by modulating the expression of P-gp and MRP-1. K562/ADM cells were stably transfected with HOXA10-targeted short hairpin RNA (shRNA). The results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis showed that the mRNA and protein expression of HOXA10 was markedly suppressed following transfection with a shRNA-containing vector. The sensitivity of the K562/ADM cells to ADR was enhanced by the silencing of HOXA10, due to the increased intracellular accumulation of ADR. The accumulation of ADR induced by the silencing of HOXA10 may be due to the downregulation of P-gp and MRP-1. Western blot analysis revealed that downregulating HOXA10 inhibited the protein expression of P-gp and MRP-1. Taken together, these results suggest that knockdown of HOXA10 combats resistance and that HOXA10 is a potential target for resistant human CML.

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1	Li H, Guo K, Wu C, Shu L, Guo S, Hou J, Zhao N, Wei L, Man X and Zhang L: Controlled and targeted drug delivery by a UV-responsive liposome for overcoming chemo-resistance in non-Hodgkin lymphoma. Chem Biol Drug. 86:783–794. 2015. View Article : Google Scholar
2	Nabekura T, Hiroi T, Kawasaki T and Uwai Y: Effects of natural nuclear factor-kappa B inhibitors on anticancer drug efflux transporter human P-glycoprotein. Biomed Pharmacother. 70:140–145. 2015. View Article : Google Scholar : PubMed/NCBI
3	Ren J, Xu Y, Huang Q, Yang J, Yang M, Hu K and Wei K: Chabamide induces cell cycle arrest and apoptosis by the Akt/MAPK pathway and inhibition of P-glycoprotein in K562/ADR cells. Anticancer Drugs. 26:498–507. 2015. View Article : Google Scholar : PubMed/NCBI
4	Wen X, Zhang HD, Zhao L, Yao YF, Zhao JH and Tang JH: Ginsenoside Rh2 differentially mediates microRNA expression to prevent chemoresistance of breast cancer. Asian Pac J Cancer Prev. 16:1105–1109. 2015. View Article : Google Scholar : PubMed/NCBI
5	Bao W, Zhu F, Duan Y, Yang Y and Cai H: HtrA1 resensitizes multidrug-resistant hepatocellular carcinoma cells by targeting XIAP. Biomed Pharmacother. 70:97–102. 2015. View Article : Google Scholar : PubMed/NCBI
6	Wang Z, Yang L, Xia Y, Guo C and Kong L: Icariin enhances cytotoxicity of doxorubicin in human multidrug-resistant osteosarcoma cells by inhibition of ABCB1 and down-regulation of the PI3K/Akt pathway. Biol Pharm Bull. 38:277–284. 2015. View Article : Google Scholar : PubMed/NCBI
7	Song YN, Guo XL, Zheng BB, Liu XY, Dong X, Yu LG and Cheng YN: Ligustrazine derivate DLJ14 reduces multidrug resistance of K562/A02 cells by modulating GSTπ activity. Toxicol In Vitro. 25:937–943. 2011. View Article : Google Scholar : PubMed/NCBI
8	Ma J, Wang T, Guo R, Yang X, Yin J, Yu J, Xiang Q, Pan X, Tang H and Lei X: Involvement of miR-133a and miR-326 in ADM resistance of HepG2 through modulating expression of ABCC1. J Drug Target. 23:519–524. 2015. View Article : Google Scholar : PubMed/NCBI
9	Yang X, Iyer AK, Singh A, Choy E, Hornicek FJ, Amiji MM and Duan Z: MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer. Sci Rep. 5:85092015. View Article : Google Scholar : PubMed/NCBI
10	Fantappiè O, Sassoli C, Tani A, Nosi D, Marchetti S, Formigli L and Mazzanti R: Mitochondria of a human multidrug-resistant hepatocellular carcinoma cell line constitutively express inducible nitric oxide synthase in the inner membrane. J Cell Mol Med. 19:1410–1417. 2015. View Article : Google Scholar : PubMed/NCBI
11	Xu X, Zhang Y, Li W, Miao H, Zhang H, Zhou Y, Li Z, You Q, Zhao L and Guo Q: Wogonin reverses multi-drug resistance of human myelogenous leukemia K562/A02 cells via downregulation of MRP1 expression by inhibiting Nrf2/ARE signaling pathway. Biochem Pharmacol. 92:220–234. 2014. View Article : Google Scholar : PubMed/NCBI
12	Bei L, Shah C, Wang H, Huang W, Roy R and Eklund EA: β-catenin activates the HOXA10 and CDX4 genes in myeloid progenitor cells. J Biol Chem. 287:39589–39601. 2012. View Article : Google Scholar : PubMed/NCBI
13	Wang H, Lindsey S, Konieczna I, Bei L, Horvath E, Huang W, Saberwal G and Eklund EA: Constitutively active SHP2 cooperates with HoxA10 overexpression to induce acute myeloid leukemia. J Biol Chem. 284:2549–2567. 2009. View Article : Google Scholar :
14	Vitiello D, Pinard R and Taylor HS: Gene expression profiling reveals putative HOXA10 downstream targets in the periimplantation mouse uterus. Reprod Sci. 15:529–535. 2008. View Article : Google Scholar : PubMed/NCBI
15	Bei L, Huang W, Wang H, Shah C, Horvath E and Eklund E: HoxA10 activates CDX4 transcription and Cdx4 activates HOXA10 transcription in myeloid cells. J Biol Chem. 286:19047–19064. 2011. View Article : Google Scholar : PubMed/NCBI
16	Magnusson M, Brun AC, Miyake N, Larsson J, Ehinger M, Bjornsson JM, Wutz A, Sigvardsson M and Karlsson S: HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development. Blood. 109:3687–3696. 2007. View Article : Google Scholar : PubMed/NCBI
17	Kim JW, Kim JY, Kim JE, Kim SK, Chung HT and Park CK: HOXA10 is associated with temozolomide resistance through regulation of the homologous recombinant DNA repair pathway in glioblastoma cell lines. Genes Cancer. 5:165–174. 2014.PubMed/NCBI
18	Gaspar N, Marshall L, Perryman L, Bax DA, Little SE, Viana-Pereira M, Sharp SY, Vassal G, Pearson AD, Reis RM, et al: MGMT-independent temozolomide resistance in pediatric glioblastoma cells associated with a PI3-kinase-mediated HOX/stem cell gene signature. Cancer Res. 70:9243–9252. 2010. View Article : Google Scholar : PubMed/NCBI
19	Wang JY, Jia XH, Xing HY, Li YJ, Fan WW, Li N and Xie SY: Inhibition of Forkhead box protein M1 by thiostrepton increases chemosensitivity to doxorubicin in T-cell acute lymphoblastic leukemia. Mol Med Rep. 12:1457–1464. 2015.PubMed/NCBI
20	Sengupta A, Banerjee D, Chandra S, Banerji SK, Ghosh R, Roy R and Banerjee S: Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression. Leukemia. 21:949–955. 2007.PubMed/NCBI
21	Abdallah HM, Al-Abd AM, El-Dine RS and El-Halawany AM: P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: a review. J Adv Res. 6:45–62. 2015. View Article : Google Scholar : PubMed/NCBI
22	Sloma I, Imren S, Beer PA, Zhao Y, Lecault V, Leung D, Raghuram K, Brimacombe C, Lambie K, Piret J, et al: Ex vivo expansion of normal and chronic myeloid leukemic stem cells without functional alteration using a NUP98HOXA10homeodomain fusion gene. Leukemia. 27:159–169. 2013. View Article : Google Scholar :
23	Yao J, Fang LC, Yang ZL, Huang H, Li Y, Deng J and Zheng J: Mixed lineage leukaemia histone methylases 1 collaborate with ERα to regulate HOXA10 expression in AML. Biosci Rep. 34:e001562014. View Article : Google Scholar
24	Zhang L, Wan Y, Jiang Y, Ma J, Liu J, Tang W, Wang X and Cheng W: Upregulation HOXA10 homeobox gene in endometrial cancer: role in cell cycle regulation. Med Oncol. 31:522014. View Article : Google Scholar : PubMed/NCBI
25	Wang XB, Wang SS, Zhang QF, Liu M, Li HL, Liu Y, Wang JN, Zheng F, Guo LY and Xiang JZ: Inhibition of tetramethylpyrazine on P-gp, MRP2, MRP3 and MRP5 in multidrug resistant human hepatocellular carcinoma cells. Oncol Rep. 23:211–215. 2010.