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Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary Research

miR-1296-5p decreases ERBB2 expression to inhibit the cell proliferation in ERBB2-positive breast cancer

Authors: Gang Chen, Mingfeng He, Yin Yin, Ting Yan, Wenfang Cheng, Zebo Huang, Lan Zhang, Huo Zhang, Ping Liu, Wei Zhu, Yichao Zhu

Published in: Cancer Cell International | Issue 1/2017

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Abstract

Background

The tumor suppressive role of miR-1296 is observed in triple negative breast cancer (TNBC). However, the effect of miR-1296-5p in ERBB2-positive breast cancers remains obscure.

Methods

Whether ERBB2 was the target gene of the miR-1296-5p was predicted by online software, and determined by dual-luciferase activity assay. miR-1296-5p expression levels were determined in breast cancer samples (114 breast cancer tissues and 30 adjacent normal tissues) by using qRT-PCR. The effect of miR-1296-5p and inhibition of ERBB2/mTORC1 signaling on the downstream target was assessed by Western blot. SK-BR-3 and BT-474 breast cancer cell line was transfected with miR-1296-5p mimic after which cell proliferation and apoptosis were determined by the clonogenic assay and the flow cytometry system, respectively. In addition, the chemotherapeutic drug sensitivity of SK-BR-3 and BT-474 cells transfected with miR-1296-5p mimic were determined by MTT assay.

Results

The luciferase assay carrying ERBB2 3′-untranslated region-based reporters expressed in SK-BR-3 and BT-474 cells suggested that ERBB2 was the target gene of miR-1296-5p. MiR-1296-5p was significantly decreased in breast cancer tissues compared to adjacent normal tissues. Moreover, it was declined in ERBB2-positive breast cancer samples compared with that in ERBB2-negative breast cancer tissues. Overexpressed miR-1296-5p reduced its target protein level and mTORC1/S6 activation, inhibited the proliferation of ERBB2-positive breast cancer cells and sensitized these cells to cisplatin and 5-fluorouracil-induced apoptosis.

Conclusions

Our findings suggest that miR-1296-5p is involved in the regulation of proliferation in breast cancer cells via targeting ERBB2/mTORC1 signaling pathway.
Literature
1.
go back to reference Fabi A, Mottolese M, Segatto O. Therapeutic targeting of ERBB2 in breast cancer: understanding resistance in the laboratory and combating it in the clinic. J Mol Med (Berl). 2014;92(7):681–95.CrossRef Fabi A, Mottolese M, Segatto O. Therapeutic targeting of ERBB2 in breast cancer: understanding resistance in the laboratory and combating it in the clinic. J Mol Med (Berl). 2014;92(7):681–95.CrossRef
2.
go back to reference Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244(4905):707–12.CrossRefPubMed Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244(4905):707–12.CrossRefPubMed
3.
go back to reference Chen H, Sun JG, Cao XW, Ma XG, Xu JP, Luo FK, Chen ZT. Preliminary validation of ERBB2 expression regulated by miR-548d-3p and miR-559. Biochem Biophys Res Commun. 2009;385(4):596–600.CrossRefPubMed Chen H, Sun JG, Cao XW, Ma XG, Xu JP, Luo FK, Chen ZT. Preliminary validation of ERBB2 expression regulated by miR-548d-3p and miR-559. Biochem Biophys Res Commun. 2009;385(4):596–600.CrossRefPubMed
4.
5.
go back to reference Yu D, Hung MC. Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene. 2000;19(53):6115–21.CrossRefPubMed Yu D, Hung MC. Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene. 2000;19(53):6115–21.CrossRefPubMed
6.
go back to reference Urruticoechea A, Rizwanullah M, Im SA, Ruiz ACS, Lang I, Tomasello G, Douthwaite H, Badovinac Crnjevic T, Heeson S, Eng-Wong J, et al. Randomized phase III trial of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy. J Clin Oncol. 2017. doi:10.1200/JCO.2016.70.6267.PubMed Urruticoechea A, Rizwanullah M, Im SA, Ruiz ACS, Lang I, Tomasello G, Douthwaite H, Badovinac Crnjevic T, Heeson S, Eng-Wong J, et al. Randomized phase III trial of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy. J Clin Oncol. 2017. doi:10.​1200/​JCO.​2016.​70.​6267.PubMed
7.
go back to reference Thavendiranathan P, Amir E. Left ventricular dysfunction with trastuzumab therapy: is primary prevention the best option? J Clin Oncol. 2017;35(8):820–5.CrossRefPubMed Thavendiranathan P, Amir E. Left ventricular dysfunction with trastuzumab therapy: is primary prevention the best option? J Clin Oncol. 2017;35(8):820–5.CrossRefPubMed
8.
go back to reference Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE Study. J Clin Oncol. 2017;35(2):141–8.CrossRefPubMed Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE Study. J Clin Oncol. 2017;35(2):141–8.CrossRefPubMed
9.
go back to reference Niu J, Xue A, Chi Y, Xue J, Wang W, Zhao Z, Fan M, Yang CH, Shao ZM, Pfeffer LM, et al. Induction of miRNA-181a by genotoxic treatments promotes chemotherapeutic resistance and metastasis in breast cancer. Oncogene. 2016;35(10):1302–13.CrossRefPubMed Niu J, Xue A, Chi Y, Xue J, Wang W, Zhao Z, Fan M, Yang CH, Shao ZM, Pfeffer LM, et al. Induction of miRNA-181a by genotoxic treatments promotes chemotherapeutic resistance and metastasis in breast cancer. Oncogene. 2016;35(10):1302–13.CrossRefPubMed
10.
go back to reference Xue J, Chi Y, Chen Y, Huang S, Ye X, Niu J, Wang W, Pfeffer LM, Shao ZM, Wu ZH, et al. MiRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity. Oncogene. 2016;35(4):448–58.CrossRefPubMed Xue J, Chi Y, Chen Y, Huang S, Ye X, Niu J, Wang W, Pfeffer LM, Shao ZM, Wu ZH, et al. MiRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity. Oncogene. 2016;35(4):448–58.CrossRefPubMed
11.
go back to reference Yuan Y, Anbalagan D, Lee LH, Samy RP, Shanmugam MK, Kumar AP, Sethi G, Lobie PE, Lim LH. ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and C-Myc to reduce breast cancer proliferation. Oncotarget. 2016;7(19):27007.CrossRefPubMedPubMedCentral Yuan Y, Anbalagan D, Lee LH, Samy RP, Shanmugam MK, Kumar AP, Sethi G, Lobie PE, Lim LH. ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and C-Myc to reduce breast cancer proliferation. Oncotarget. 2016;7(19):27007.CrossRefPubMedPubMedCentral
12.
go back to reference Majid S, Dar AA, Saini S, Chen Y, Shahryari V, Liu J, Zaman MS, Hirata H, Yamamura S, Ueno K, et al. Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer. Cancer Res. 2010;70(7):2809–18.CrossRefPubMed Majid S, Dar AA, Saini S, Chen Y, Shahryari V, Liu J, Zaman MS, Hirata H, Yamamura S, Ueno K, et al. Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer. Cancer Res. 2010;70(7):2809–18.CrossRefPubMed
13.
go back to reference Liu ZY, He WH, Gao JL, Luo JH, Huang X, Gao CF. Computational prediction and experimental validation of a novel synthesized pan-PIM inhibitor PI003 and its apoptosis-inducing mechanisms in cervical cancer. Oncotarget. 2015;6(10):8019–35.CrossRefPubMedPubMedCentral Liu ZY, He WH, Gao JL, Luo JH, Huang X, Gao CF. Computational prediction and experimental validation of a novel synthesized pan-PIM inhibitor PI003 and its apoptosis-inducing mechanisms in cervical cancer. Oncotarget. 2015;6(10):8019–35.CrossRefPubMedPubMedCentral
14.
go back to reference Boo L, Ho WY, Ali NM, Yeap SK, Ky H, Chan KG, Yin WF, Satharasinghe DA, Liew WC, Tan SW, et al. MiRNA transcriptome profiling of spheroid-enriched cells with cancer stem cell properties in human breast MCF-7 cell line. Int J Biol Sci. 2016;12(4):427–45.CrossRefPubMedPubMedCentral Boo L, Ho WY, Ali NM, Yeap SK, Ky H, Chan KG, Yin WF, Satharasinghe DA, Liew WC, Tan SW, et al. MiRNA transcriptome profiling of spheroid-enriched cells with cancer stem cell properties in human breast MCF-7 cell line. Int J Biol Sci. 2016;12(4):427–45.CrossRefPubMedPubMedCentral
15.
go back to reference Phan B, Majid S, Ursu S, de Semir D, Nosrati M, Bezrookove V, Kashani-Sabet M, Dar AA. Tumor suppressor role of microRNA-1296 in triple-negative breast cancer. Oncotarget. 2016;7(15):19519.CrossRefPubMedPubMedCentral Phan B, Majid S, Ursu S, de Semir D, Nosrati M, Bezrookove V, Kashani-Sabet M, Dar AA. Tumor suppressor role of microRNA-1296 in triple-negative breast cancer. Oncotarget. 2016;7(15):19519.CrossRefPubMedPubMedCentral
16.
go back to reference Liu J, Zhang Y, Xu R, Du J, Hu Z, Yang L, Chen Y, Zhu Y, Gu L. PI3K/Akt-dependent phosphorylation of GSK3beta and activation of RhoA regulate Wnt5a-induced gastric cancer cell migration. Cell Signal. 2013;25(2):447–56.CrossRefPubMed Liu J, Zhang Y, Xu R, Du J, Hu Z, Yang L, Chen Y, Zhu Y, Gu L. PI3K/Akt-dependent phosphorylation of GSK3beta and activation of RhoA regulate Wnt5a-induced gastric cancer cell migration. Cell Signal. 2013;25(2):447–56.CrossRefPubMed
17.
go back to reference Zhao DS, Chen Y, Jiang H, Lu JP, Zhang G, Geng J, Zhang Q, Shen JH, Zhou X, Zhu W, et al. Serum miR-210 and miR-30a expressions tend to revert to fetal levels in Chinese adult patients with chronic heart failure. Cardiovasc Pathol. 2013;22(6):444–50.CrossRefPubMed Zhao DS, Chen Y, Jiang H, Lu JP, Zhang G, Geng J, Zhang Q, Shen JH, Zhou X, Zhu W, et al. Serum miR-210 and miR-30a expressions tend to revert to fetal levels in Chinese adult patients with chronic heart failure. Cardiovasc Pathol. 2013;22(6):444–50.CrossRefPubMed
18.
go back to reference Johnson E, Seachrist DD, DeLeon-Rodriguez CM, Lozada KL, Miedler J, Abdul-Karim FW, Keri RA. HER2/ErbB2-induced breast cancer cell migration and invasion require p120 catenin activation of Rac1 and Cdc42. J Biol Chem. 2010;285(38):29491–501.CrossRefPubMedPubMedCentral Johnson E, Seachrist DD, DeLeon-Rodriguez CM, Lozada KL, Miedler J, Abdul-Karim FW, Keri RA. HER2/ErbB2-induced breast cancer cell migration and invasion require p120 catenin activation of Rac1 and Cdc42. J Biol Chem. 2010;285(38):29491–501.CrossRefPubMedPubMedCentral
19.
go back to reference Tornillo G, Bisaro B, Camacho-Leal Mdel P, Galie M, Provero P, Di Stefano P, Turco E, Defilippi P, Cabodi S. p130Cas promotes invasiveness of three-dimensional ErbB2-transformed mammary acinar structures by enhanced activation of mTOR/p70S6K and Rac1. Eur J Cell Biol. 2011;90(2–3):237–48.CrossRefPubMed Tornillo G, Bisaro B, Camacho-Leal Mdel P, Galie M, Provero P, Di Stefano P, Turco E, Defilippi P, Cabodi S. p130Cas promotes invasiveness of three-dimensional ErbB2-transformed mammary acinar structures by enhanced activation of mTOR/p70S6K and Rac1. Eur J Cell Biol. 2011;90(2–3):237–48.CrossRefPubMed
20.
go back to reference Lee JE, Hong EJ, Nam HY, Kim JW, Han BG, Jeon JP. MicroRNA signatures associated with immortalization of EBV-transformed lymphoblastoid cell lines and their clinical traits. Cell Proliferat. 2011;44(1):59–66.CrossRef Lee JE, Hong EJ, Nam HY, Kim JW, Han BG, Jeon JP. MicroRNA signatures associated with immortalization of EBV-transformed lymphoblastoid cell lines and their clinical traits. Cell Proliferat. 2011;44(1):59–66.CrossRef
21.
go back to reference Cakmak HA, Coskunpinar E, Ikitimur B, Barman HA, Karadag B, Tiryakioglu NO, Kahraman K, Vural VA. The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study. J Cardiovasc Med (Hagerstown). 2015;16(6):431–7.CrossRef Cakmak HA, Coskunpinar E, Ikitimur B, Barman HA, Karadag B, Tiryakioglu NO, Kahraman K, Vural VA. The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study. J Cardiovasc Med (Hagerstown). 2015;16(6):431–7.CrossRef
22.
go back to reference Klos KS, Wyszomierski SL, Sun M, Tan M, Zhou X, Li P, Yang W, Yin G, Hittelman WN, Yu D. ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6 K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res. 2006;66(4):2028–37.CrossRefPubMed Klos KS, Wyszomierski SL, Sun M, Tan M, Zhou X, Li P, Yang W, Yin G, Hittelman WN, Yu D. ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6 K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res. 2006;66(4):2028–37.CrossRefPubMed
Metadata
Title
miR-1296-5p decreases ERBB2 expression to inhibit the cell proliferation in ERBB2-positive breast cancer
Authors
Gang Chen
Mingfeng He
Yin Yin
Ting Yan
Wenfang Cheng
Zebo Huang
Lan Zhang
Huo Zhang
Ping Liu
Wei Zhu
Yichao Zhu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0466-y

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