PRB inhibited cell proliferation through let-7b-E2F1 in breast cancer

in Endocrine-Related Cancer
Authors:
Teeranut Asavasupreechar Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Tōhoku, Japan

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Ryoko Saito-Koyama Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Tōhoku, Japan
Department of Pathology, National Hospital Organization, Sendai Medical Center, Sendai, Miyagi, Tōhoku, Japan

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Yasuhiro Miki Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Tōhoku, Japan

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Keiichi Tamai Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Miyagi, Tōhoku, Japan

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Jiro Abe Division of Thoracic Surgery, Miyagi Cancer Center, Natori, Miyagi, Tōhoku, Japan

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Chihiro Inoue Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Tōhoku, Japan

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Ikuro Sato Division of Pathology, Miyagi Cancer Center, Natori, Miyagi, Tōhoku, Japan

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Viroj Boonyaratanakornkit Department of Clinical Chemistry and Age-related Inflammation and Degeneration Research Unit, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand

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Hironobu Sasano Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Tōhoku, Japan

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Correspondence should be addressed to R Saito-Koyama: saitoarlu@patholo2.med.tohoku.ac.jp
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The presence of progesterone receptor (PR) and PR isoform B (PRB) in breast cancer is generally correlated with better clinical outcomes. Additionally, the significance of hormone-independent effects of PR/PRB correlated with better prognosis has been reported in non-small cell lung cancer (NSCLC). However, the detailed mechanism of that still remains unclear. In this study, we examined how microRNAs (miRNAs) could contribute to tumor inhibition via PR/PRB expression, in order to find miRNAs that have tumor-agnostic effects between breast cancer and NSCLC. We obtained miRNA data using human tissues of breast cancer and NSCLC from The Cancer Genome Atlas (TCGA) database and PCR array from NSCLC patients of our cohort. Subsequently, we examined the function of the miRNA through in vitro study using breast cancer cell lines. As a result, only let-7b expression was significantly correlated with PR expression in both cancers. Additionally, the expression of let-7b significantly inhibited cell proliferation by inducing PR and PRB expression in breast cancer cell lines. However, the positive correlation of let-7b and PRB required a mediated factor, E2 promoter binding factor 1 (E2F1), obtained from TCGA database analysis. In vitro experiments showed that let-7b significantly inhibited E2F1, and E2F1 significantly inhibited PRB. This study revealed that PRB inhibits the proliferation of breast cancer cells by the let-7b-E2F1 interaction. In addition, the immunohistochemical analysis in NSCLC was also consistent with these in vitro data. Our results could contribute to developing novel therapeutic strategies for patients with PR/PRB-positive cancer by targeting let-7b or PRB expression in breast cancer and possibly NSCLC.

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  • Akao Y, Nakagawa Y & & Naoe T 2006 Let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biological and Pharmaceutical Bulletin 29 903906. (https://doi.org/10.1248/bpb.29.903)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Alberg AJ & & Samet JM 2003 Epidemiology of lung cancer. Chest 123(Supplement) 21S49S. (https://doi.org/10.1378/chest.123.1_suppl.21s)

  • Asavasupreechar T, Saito R, Edwards DP, Sasano H & & Boonyaratanakornkit V 2019 Progesterone receptor isoform B expression in pulmonary neuroendocrine cells decreases cell proliferation. Journal of Steroid Biochemistry and Molecular Biology 190 212223. (https://doi.org/10.1016/j.jsbmb.2019.03.022)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Asavasupreechar T, Saito R, Miki Y, Edwards DP, Boonyaratanakornkit V & & Sasano H 2020 Systemic distribution of progesterone receptor subtypes in human tissues. Journal of Steroid Biochemistry and Molecular Biology 199 105599. (https://doi.org/10.1016/j.jsbmb.2020.105599)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bamberger AM, Milde-Langosch K, Schulte HM & & Löning T 2000 Progesterone receptor isoforms, PR-B and PR-A, in breast cancer: correlations with clinicopathologic tumor parameters and expression of AP-1 factors. Hormone Research 54 3237. (https://doi.org/10.1159/000063434)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Boonyaratanakornkit V, Mcgowan E, Sherman L, Mancini MA, Cheskis BJ & & Edwards DP 2007 The role of extranuclear signaling actions of progesterone receptor in mediating progesterone regulation of gene expression and the cell cycle. Molecular Endocrinology 21 359375. (https://doi.org/10.1210/me.2006-0337)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Calvo V & & Beato M 2011 BRCA1 counteracts progesterone action by ubiquitination leading to progesterone receptor degradation and epigenetic silencing of target promoters. Cancer Research 71 34223431. (https://doi.org/10.1158/0008-5472.CAN-10-3670)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Castro D, Moreira M, Gouveia AM, Pozza DH & & De Mello RA 2017 MicroRNAs in lung cancer. Oncotarget 8 8167981685. (https://doi.org/10.18632/oncotarget.20955)

  • Chun SM, Park HJ, Kim CH & & Kim I 2011 The significance of microRNA Let-7b, miR-30c, and miR-200c expression in breast cancers. Korean Journal of Pathology 45 354360. (https://doi.org/10.4132/KoreanJPathol.2011.45.4.354)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Clemm DL, Sherman L, Boonyaratanakornkit V, Schrader WT, Weigel NL & & Edwards DP 2000 Differential hormone-dependent phosphorylation of progesterone receptor A and B forms revealed by a phosphoserine site-specific monoclonal antibody. Molecular Endocrinology 14 5265. (https://doi.org/10.1210/mend.14.1.0413)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Conneely OM & & Lydon JP 2000 Progesterone receptors in reproduction: functional impact of the A and B isoforms. Steroids 65 571577. (https://doi.org/10.1016/s0039-128x(0000115-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • De Amicis F, Guido C, Santoro M, Lanzino M, Panza S, Avena P, Panno ML, Perrotta I, Aquila S & & Andò S 2014 A novel functional interplay between progesterone receptor‐B and PTEN, via AKT, modulates autophagy in breast cancer cells. Journal of Cellular and Molecular Medicine 18 22522265. (https://doi.org/10.1111/jcmm.12363)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Denechaud PD, Fajas L & & Giralt A 2017 E2F1, a novel regulator of metabolism. Frontiers in Endocrinology 8 311. (https://doi.org/10.3389/fendo.2017.00311)

  • Detre S, Saclani Jotti G & & Dowsett M 1995 A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. Journal of Clinical Pathology 48 876878. (https://doi.org/10.1136/jcp.48.9.876)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Di Fazio P, Montalbano R, Neureiter D, Alinger B, Schmidt A, Merkel AL, Quint K & & Ocker M 2012 Downregulation of HMGA2 by the pan-deacetylase inhibitor panobinostat is dependent on hsa-let-7b expression in liver cancer cell lines. Experimental Cell Research 318 18321843. (https://doi.org/10.1016/j.yexcr.2012.04.018)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Goulding H, Pinder S, Cannon P, Pearson D, Nicholson R, Snead D, Bell J, Elston CW, Robertson JF & & Blamey RW 1995 A new immunohistochemical antibody for the assessment of estrogen receptor status on routine formalin-fixed tissue samples. Human Pathology 26 291294. (https://doi.org/10.1016/0046-8177(9590060-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hammond MEH, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, et al.2010 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Journal of Clinical Oncology 28 27842795. (https://doi.org/10.1200/JCO.2009.25.6529)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hsu L-H, Liu K-J, Tsai M-F, Wu C-R, Feng A-C, Chu N-M & & Kao S-H 2015 Estrogen adversely affects the prognosis of patients with lung adenocarcinoma. Cancer Science 106 5159. (https://doi.org/10.1111/cas.12558)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Huang CL, Liu D, Nakano J, Yokomise H, Ueno M, Kadota K & & Wada H 2007 E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non–small-cell lung cancer. Clinical Cancer Research 13 69386946. (https://doi.org/10.1158/1078-0432.CCR-07-1539)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hui L, Zheng F, Bo Y, Sen-Lin M, Ai-Jun L, Wei-Ping Z, Yong-Jie Z & & Lei Y 2020 MicroRNA let-7b inhibits cell proliferation via upregulation of p21 in hepatocellular carcinoma. Cell and Bioscience 10 83. (https://doi.org/10.1186/s13578-020-00443-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ishibashi H, Suzuki T, Suzuki S, Niikawa H, Lu L, Miki Y, Moriya T, Hayashi S-I, Handa M, Kondo T, et al.2005 Progesterone receptor in non–small cell lung cancer—a potent prognostic factor and possible target for endocrine therapy. Cancer Research 65 64506458. (https://doi.org/10.1158/0008-5472.CAN-04-3087)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jacobsen BM & & Horwitz KB 2012 Progesterone receptors, their isoforms and progesterone regulated transcription. Molecular and Cellular Endocrinology 357 1829. (https://doi.org/10.1016/j.mce.2011.09.016)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, Wilson M, Wang X, Shelton J, Shingara J, et al.2007 The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Research 67 77137722. (https://doi.org/10.1158/0008-5472.CAN-07-1083)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Johnson DG, Ohtani K & & Nevins JR 1994 Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression. Genes and Development 8 15141525. (https://doi.org/10.1101/gad.8.13.1514)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jonsdottir K, Janssen SR, Da Rosa FC, Gudlaugsson E, Skaland I, Baak JPA & & Janssen EAM 2012 Validation of expression patterns for nine miRNAs in 204 lymph-node negative breast cancers. PLoS One 7 e48692. (https://doi.org/10.1371/journal.pone.0048692)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kajita S, Suzuki E & & Saegusa M 2012 Progesterone receptor expression correlates with estrogen receptor α but not βand pS2 status in ovarian carcinomas: relation to apoptosis, cell proliferation, p27Kip1 expression, and survival. Kitasato Medical Journal 42 2232.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H & & Chambon P 1990 Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO Journal 9 1603–1614. (https://doi.org/10.1002/j.1460-2075.1990.tb08280.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kawaguchi T, Takada M, Kubo A, Matsumura A, Fukai S, Tamura A, Saito R, Kawahara M & & Maruyama Y 2010 Gender, histology, and time of diagnosis are important factors for prognosis: analysis of 1499 never-smokers with advanced non-small cell lung cancer in Japan. Journal of Thoracic Oncology 5 10111017. (https://doi.org/10.1097/JTO.0b013e3181dc213e)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kawprasertsri S, Pietras RJ, Marquez-Garban DC & & Boonyaratanakornkit V 2016 Progesterone receptor (PR) polyproline domain (PPD) mediates inhibition of epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer cells. Cancer Letters 374 279291. (https://doi.org/10.1016/j.canlet.2016.02.014)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kumar R, Moure CM, Khan SH, Callaway C, Grimm SL, Goswami D, Griffin PR & & Edwards DP 2013 Regulation of the structurally dynamic N-terminal domain of progesterone receptor by protein-induced folding. Journal of Biological Chemistry 288 3028530299. (https://doi.org/10.1074/jbc.M113.491787)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Leonhardt SA, Boonyaratanakornkit V & & Edwards DP 2003 Progesterone receptor transcription and non-transcription signaling mechanisms. Steroids 68 761770. (https://doi.org/10.1016/s0039-128x(0300129-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mahmoudian-Sani MR, Mehri-Ghahfarrokhi A, Asadi-Samani M & & Mobini GR 2017 Serum miRNAs as biomarkers for the diagnosis and prognosis of thyroid cancer: a comprehensive review of the literature. European Thyroid Journal 6 171177. (https://doi.org/10.1159/000468520)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Marquez-Garban DC, Mah V, Alavi M, Maresh EL, Chen HW, Bagryanova L, Horvath S, Chia D, Garon E, Goodglick L, et al.2011 Progesterone and estrogen receptor expression and activity in human non-small cell lung cancer. Steroids 76 910920. (https://doi.org/10.1016/j.steroids.2011.04.015)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Miki Y, Abe K, Suzuki S, Suzuki T & & Sasano H 2011 Suppression of estrogen actions in human lung cancer. Molecular and Cellular Endocrinology 340 168174. (https://doi.org/10.1016/j.mce.2011.02.018)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Miyashita M, Sasano H, Tamaki K, Hirakawa H, Takahashi Y, Nakagawa S, Watanabe G, Tada H, Suzuki A, Ohuchi N, et al.2015 Prognostic significance of tumor-infiltrating CD8(+) and FOXP3(+) lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer: a retrospective multicenter study. Breast Cancer Research 17 124. (https://doi.org/10.1186/s13058-015-0632-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mu X & & Chang C 2003 TR3 orphan nuclear receptor mediates apoptosis through up-regulating E2F1 in human prostate cancer LNCaP cells. Journal of Biological Chemistry 278 4284042845. (https://doi.org/10.1074/jbc.M305594200)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pateetin P, Hutvagner G, Bajan S, Padula MP, Mcgowan EM & & Boonyaratanakornkit V 2021 Author Correction: triple SILAC identified progestin-independent and dependent PRA and PRB interacting partners in breast cancer. Scientific Data 8 145. (https://doi.org/10.1038/s41597-021-00928-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Reiner A, Neumeister B, Spona J, Reiner G, Schemper M & & Jakesz R 1990 Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer. Cancer Research 50 70577061.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Renthal NE, Chen CC, Williams KC, Gerard RD, Prange-Kiel J & & Mendelson CR 2010 miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor. Proceedings of the National Academy of Sciences of the United States of America 107 2082820833. (https://doi.org/10.1073/pnas.1008301107)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rodriguez-Lara V, Pena-Mirabal E, Baez-Saldana R, Esparza-Silva AL, Garcia-Zepeda E, Cerbon Cervantes MA, Diaz D & & Fortoul TI 2014 Estrogen receptor beta and CXCR4/CXCL12 expression: differences by sex and hormonal status in lung adenocarcinoma. Archives of Medical Research 45 158169. (https://doi.org/10.1016/j.arcmed.2014.01.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rudd MD, Gonzalez-Robayna I, Hernandez-Gonzalez I, Weigel NL, Bingman WE 3RD & & Richards JS 2007 Constitutively active FOXO1a and a DNA-binding domain mutant exhibit distinct co-regulatory functions to enhance progesterone receptor A activity. Journal of Molecular Endocrinology 38 673690. (https://doi.org/10.1677/JME-07-0017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Santoro IL, Ramos RP, Franceschini J, Jamnik S & & Fernandes ALG 2011 Non-small cell lung cancer in never smokers: a clinical entity to be identified. Clinics 66 18731877. (https://doi.org/10.1590/s1807-59322011001100005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Stabile LP, Dacic S, Land SR, Lenzner DE, Dhir R, Acquafondata M, Landreneau RJ, Grandis JR & & Siegfried JM 2011 Combined analysis of estrogen receptor beta-1 and progesterone receptor expression identifies lung cancer patients with poor outcome. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research 17 154164. (https://doi.org/10.1158/1078-0432.CCR-10-0992)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A & & Bray F 2021 Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians 71 209249. (https://doi.org/10.3322/caac.21660)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, et al.2004 Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Research 64 37533756. (https://doi.org/10.1158/0008-5472.CAN-04-0637)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tarangelo A, Lo N, Teng R, Kim E, Le L, Watson D, Furth EE, Raman P, Ehmer U & & Viatour P 2015 Recruitment of Pontin/Reptin by E2F1 amplifies E2F transcriptional response during cancer progression. Nature Communications 6 10028. (https://doi.org/10.1038/ncomms10028)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wade HE, Kobayashi S, Eaton ML, Jansen MS, Lobenhofer EK, Lupien M, Geistlinger TR, Zhu W, Nevins JR, Brown M, et al.2010 Multimodal regulation of E2F1 gene expression by progestins. Molecular and Cellular Biology 30 18661877. (https://doi.org/10.1128/MCB.01060-09)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang S, Wang Z, Wang Q, Cui Y & & Luo S 2019 Clinical significance of the expression of miRNA-21, miRNA-31 and miRNA-let7 in patients with lung cancer. Saudi Journal of Biological Sciences 26 777781. (https://doi.org/10.1016/j.sjbs.2018.12.009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wendler A, Keller D, Albrecht C, Peluso JJ & & Wehling M 2011 Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells. Oncology Reports 25 273279. (https://doi.org/10.3892/or_00001071)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yang Z & & Wang L 2011 Regulation of microRNA expression and function by nuclear receptor signaling. Cell and Bioscience 1 3131. (https://doi.org/10.1186/2045-3701-1-31)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang K, Wang W, Liu Y, Guo A & & Yang D 2019 Let-7b acts as a tumor suppressor in osteosarcoma via targeting IGF1R. Oncology Letters 17 16461654. (https://doi.org/10.3892/ol.2018.9793)

    • PubMed
    • Search Google Scholar
    • Export Citation