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12.11.2015 | Original Article

Involvement of Numb-mediated HIF-1α inhibition in anti-proliferative effect of PNA-antimiR-182 in trastuzumab-sensitive and -resistant SKBR3 cells

verfasst von: Soraya Sajadimajd, Razieh Yazdanparast, Sadeghirizi Akram

Erschienen in: Tumor Biology | Ausgabe 4/2016

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Abstract

Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2) that is overexpressed in about 25 % of breast cancer patients. However, primary and/or acquired resistance to trastuzumab develops in most affected persons. In this study, we explored the functional role of miR-182 inhibition with aiming the sensitization of SKBR3 cells to trastuzumab. Cell viability, apoptosis, colony formation, and migration capacities of SKBR3^S (sensitive) and SKBR3^R (resistant) cells were assessed to determine the anti-proliferative effects of PNA-antimiR-182. In addition, the expression levels of miR-182, mRNA of FOXO1, and Bim as well as the protein levels of HER2 and Notch1 signaling factors were evaluated by stem-loop RT-qPCR, RT-qPCR, and Western blot, respectively. The results indicated that miR-182 might play a causal role in the mechanism of trastuzumab. In line with that, PNA-antimiR-182 inhibited synergistically the viability of both the sensitive and resistant cell groups. Furthermore, the inhibitory effect of PNA-anitmiR-182 on migration in SKBR3 cells was more than the induction of apoptosis. In addition, PNA-antimiR-182 reduced the levels of NICD, Hes1, HIF-1α, and p-Akt in both cell groups, while it augmented the intracellular content of FOXO1 and Numb suppressor proteins. In other words, PNA-antimiR-182-mediated upregulation of Numb was associated with downregulation of HIF-1α and Hes1. Consequently, downregulation of miR-182 might find therapeutical value for overcoming trastuzumab resistance.

Engel RH, Kaklamani VG. HER2-positive breast cancer. Drugs. 2007;67(9):1329–41.CrossRefPubMed

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.CrossRefPubMed

Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244(4905):707–12.CrossRefPubMed

Lohrisch C, Piccart M, (ed). An overview of HER2. Seminars in Oncology; 2001: Elsevier.

Tseng P-H, Wang Y-C, Weng S-C, Weng J-R, Chen C-S, Brueggemeier RW, et al. Overcoming trastuzumab resistance in HER2-overexpressing breast cancer cells by using a novel celecoxib-derived phosphoinositide-dependent kinase-1 inhibitor. Mol Pharmacol. 2006;70(5):1534–41.CrossRefPubMed

Opalinska JB, Gewirtz AM. Nucleic-acid therapeutics: basic principles and recent applications. Nat Rev Drug Discov. 2002;1(7):503–14.CrossRefPubMed

Kim R, Tanabe K, Uchida Y, Emi M, Inoue H, Toge T. Current status of the molecular mechanisms of anticancer drug-induced apoptosis. Cancer Chemother Pharmacol. 2002;50(5):343–52.CrossRefPubMed

Tan M, Yu D. Molecular mechanisms of erbB2-mediated breast cancer chemoresistance. Breast Cancer Chemosensitivity. Springer; 2007.119-29.

Iorio MV, Ferracin M, Liu C-G, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.CrossRefPubMed

10.

Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64(11):3753–6.CrossRefPubMed

11.

Michael MZ, O'Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia 11 note: Susan M. O'Connor and Nicholas G. van Holst Pellekaan contributed equally to this work. Mol Cancer Res. 2003;1(12):882–91.PubMed

12.

Singh R, Mo Y-Y. Role of microRNAs in breast cancer. Cancer Biol Ther. 2013;14(3):201–12.CrossRefPubMedPubMedCentral

13.

Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C, et al. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res. 2009;11(3):R27.CrossRefPubMedPubMedCentral

14.

Volinia S, Galasso M, Sana ME, Wise TF, Palatini J, Huebner K, et al. Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA. Proc Natl Acad Sci. 2012;109(8):3024–9.CrossRefPubMedPubMedCentral

15.

Gong C, Yao Y, Wang Y, Liu B, Wu W, Chen J, et al. Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J Biol Chem. 2011;286(21):19127–37.CrossRefPubMedPubMedCentral

16.

Ye X, Bai W, Zhu H, Zhang X, Chen Y, Wang L, et al. MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN. BMB Rep. 2014;47(5):268–73.CrossRefPubMedPubMedCentral

17.

Ye X-M, Zhu H-Y, Bai W-D, Wang T, Wang L, Chen Y, et al. Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive breast cancer by targeting IGF1R. BMC Cancer. 2014;14(1):134.CrossRefPubMedPubMedCentral

18.

Xu S, Witmer PD, Lumayag S, Kovacs B, Valle D. MicroRNA (miRNA) transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster. J Biol Chem. 2007;282(34):25053–66.CrossRefPubMed

19.

Kong WQ, Bai R, Liu T, Cai CL, Liu M, Li X, et al. MicroRNA‐182 targets cAMP‐responsive element‐binding protein 1 and suppresses cell growth in human gastric adenocarcinoma. FEBS J. 2012;279(7):1252–60.CrossRefPubMed

20.

Sun Y, Fang R, Li C, Li L, Li F, Ye X, et al. Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro. Biochem Biophys Res Commun. 2010;396(2):501–7.CrossRefPubMed

21.

Wang PY, Gong HT, Li BF, Lv CL, Wang HT, Zhou HH, et al. Higher expression of circulating miR-182 as a novel biomarker for breast cancer. Oncol Lett. 2013;6(6):1681–6.PubMedPubMedCentral

22.

Lengyel F, Vértes Z, Kovács KA, Környei JL, Sümegi B, Vértes M. Effect of estrogen and inhibition of phosphatidylinositol-3 kinase on Akt and FOXO1 in rat uterus. Steroids. 2007;72(5):422–8.CrossRefPubMed

23.

Jackson JG, Kreisberg JI, Koterba AP, Yee D, Brattain MG. Phosphorylation and nuclear exclusion of the forkhead transcription factor FKHR after epidermal growth factor treatment in human breast cancer cells. Oncogene. 2000;19(40):4574–81.CrossRefPubMed

24.

Huang H, Regan KM, Wang F, Wang D, Smith DI, van Deursen JM, et al. Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proc Natl Acad Sci U S A. 2005;102(5):1649–54.CrossRefPubMedPubMedCentral

25.

Matsuzaki H, Daitoku H, Hatta M, Aoyama H, Yoshimochi K, Fukamizu A. Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation. Proc Natl Acad Sci U S A. 2005;102(32):11278–83.CrossRefPubMedPubMedCentral

26.

Chakrabarty A, Bhola NE, Sutton C, Ghosh R, Kuba MG, Dave B, et al. Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors. Cancer Res. 2013;73(3):1190–200.CrossRefPubMed

27.

Galili N, Davis RJ, Fredericks WJ, Mukhopadhyay S, Rauscher FJ, Emanuel BS, et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993;5(3):230–5.CrossRefPubMed

28.

Linardic CM. PAX3–FOXO1 fusion gene in rhabdomyosarcoma. Cancer Lett. 2008;270(1):10–8.CrossRefPubMedPubMedCentral

29.

Kitamura T, Kitamura YI, Funahashi Y, Shawber CJ, Castrillon DH, Kollipara R, et al. A Foxo/Notch pathway controls myogenic differentiation and fiber type specification. J Clin Invest. 2007;117(9):2477.CrossRefPubMedPubMedCentral

30.

Mittal S, Subramanyam D, Dey D, Kumar RV, Rangarajan A. Cooperation of Notch and Ras/MAPK signaling pathways in human breast carcinogenesis. Mol Cancer. 2009;8(1):128.CrossRefPubMedPubMedCentral

31.

Osipo C, Patel P, Rizzo P, Clementz A, Hao L, Golde T, et al. ErbB-2 inhibition activates Notch-1 and sensitizes breast cancer cells to a γ-secretase inhibitor. Oncogene. 2008;27(37):5019–32.CrossRefPubMed

32.

Sajadimajd S, Yazdanparast R. Differential behaviors of trastuzumab-sensitive and -resistant SKBR3 cells treated with menadione reveal the involvement of Notch1/Akt/FOXO1 signaling elements. Mol Cell Biochem. 2015:1-14.

33.

Moskwa P, Buffa FM, Pan Y, Panchakshari R, Gottipati P, Muschel RJ, et al. miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol Cell. 2011;41(2):210–20.CrossRefPubMed

34.

Fu Z, Tindall D. FOXOs, cancer and regulation of apoptosis. Oncogene. 2008;27(16):2312–9.CrossRefPubMedPubMedCentral

35.

Roy SK, Srivastava RK, Shankar S. Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer. J Mol Signal. 2010;5(1):10.CrossRefPubMedPubMedCentral

36.

Weeraratne SD, Amani V, Teider N, Pierre-Francois J, Winter D, Kye MJ, et al. Pleiotropic effects of miR-183~96~182 converge to regulate cell survival, proliferation and migration in medulloblastoma. Acta Neuropathol. 2012;123(4):539–52.CrossRefPubMed

37.

Wang YQ, Guo RD, Guo RM, Sheng W, Yin LR. MicroRNA‐182 promotes cell growth, invasion, and chemoresistance by targeting programmed cell death 4 (PDCD4) in human ovarian carcinomas. J Cell Biochem. 2013;114(7):1464–73.CrossRefPubMed

38.

Cekaite L, Rantala JK, Bruun J, Guriby M, Ågesen TH, Danielsen SA, et al. MiR-9, -31, and-182 deregulation promote proliferation and tumor cell survival in colon cancer. Neoplasia. 2012;14(9):868–IN21.CrossRefPubMedPubMedCentral

39.

Lei R, Tang J, Zhuang X, Deng R, Li G, Yu J, et al. Suppression of MIM by microRNA-182 activates RhoA and promotes breast cancer metastasis. Oncogene. 2014;33(10):1287–96.CrossRefPubMed

40.

Goto T, Takano M, Albergaria A, Briese J, Pomeranz K, Cloke B, et al. Mechanism and functional consequences of loss of FOXO1 expression in endometrioid endometrial cancer cells. Oncogene. 2008;27(1):9–19.CrossRefPubMed

41.

Li J, Yang L, Song L, Xiong H, Wang L, Yan X, et al. Astrocyte elevated gene-1 is a proliferation promoter in breast cancer via suppressing transcriptional factor FOXO1. Oncogene. 2009;28(36):3188–96.CrossRefPubMed

42.

Guttilla IK, White BA. Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. J Biol Chem. 2009;284(35):23204–16.CrossRefPubMedPubMedCentral

43.

Myatt SS, Wang J, Monteiro LJ, Christian M, Ho K-K, Fusi L, et al. Definition of microRNAs that repress expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res. 2010;70(1):367–77.CrossRefPubMed

44.

Clark AS, West K, Streicher S, Dennis PA. Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther. 2002;1(9):707–17.PubMed

45.

Dansen TB, Burgering BM. Unravelling the tumor-suppressive functions of FOXO proteins. Trends Cell Biol. 2008;18(9):421–9.CrossRefPubMed

46.

Chen C-C, Jeon S-M, Bhaskar PT, Nogueira V, Sundararajan D, Tonic I, et al. FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor. Dev Cell. 2010;18(4):592–604.CrossRefPubMedPubMedCentral

47.

Maxwell P, Dachs G, Gleadle J, Nicholls L, Harris A, Stratford I, et al. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci. 1997;94(15):8104–9.CrossRefPubMedPubMedCentral

48.

Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu M-M, et al. Modulation of hypoxia-inducible factor 1α expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res. 2000;60(6):1541–5.PubMed

49.

Minet E, Arnould T, Michel G, Roland I, Mottet D, Raes M, et al. ERK activation upon hypoxia: involvement in HIF-1 activation. FEBS Lett. 2000;468(1):53–8.CrossRefPubMed

50.

Mazure NM, Chen EY, Laderoute KR, Giaccia AJ. Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element. Blood. 1997;90(9):3322–31.PubMed

51.

Whelan KA, Schwab LP, Karakashev SV, Franchetti L, Johannes GJ, Seagroves TN, et al. The oncogene HER2/neu (ERBB2) requires the hypoxia-inducible factor HIF-1 for mammary tumor growth and anoikis resistance. J Biol Chem. 2013;288(22):15865–77.CrossRefPubMedPubMedCentral

52.

Laughner E, Taghavi P, Chiles K, Mahon PC, Semenza GL. HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1α (HIF-1α) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol. 2001;21(12):3995–4004.CrossRefPubMedPubMedCentral

53.

Michiels C, Minet E, Michel G, Mottet D, Piret JP, Raes M. HIF‐1 and AP‐1 cooperate to increase gene expression in hypoxia: role of MAP kinases. Iubmb Life. 2001;52(1):49–53.CrossRefPubMed

54.

Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, et al. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell. 2005;9(5):617–28.CrossRefPubMed

55.

Qiang L, Wu T, Zhang H, Lu N, Hu R, Wang Y, et al. HIF-1α is critical for hypoxia-mediated maintenance of glioblastoma stem cells by activating Notch signaling pathway. Cell Death Differ. 2012;19(2):284–94.CrossRefPubMed

Titel: Involvement of Numb-mediated HIF-1α inhibition in anti-proliferative effect of PNA-antimiR-182 in trastuzumab-sensitive and -resistant SKBR3 cells
verfasst von: Soraya Sajadimajd
Razieh Yazdanparast
Sadeghirizi Akram
Publikationsdatum: 12.11.2015
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 4/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4297-y

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Involvement of Numb-mediated HIF-1α inhibition in anti-proliferative effect of PNA-antimiR-182 in trastuzumab-sensitive and -resistant SKBR3 cells

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