Top

Published in:

Open Access 01-12-2021 | Prostate Cancer | Research

Role of miR-182/PDCD4 axis in aggressive behavior of prostate cancer in the African Americans

Authors: Marisa Shiina, Yutaka Hashimoto, Priyanka Kulkarni, Pritha Dasgupta, Varahram Shahryari, Soichiro Yamamura, Yuichiro Tanaka, Rajvir Dahiya

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Prostate cancer is one of the most commonly diagnosed cancers among men. African Americans (AA) are at an increased risk of developing prostate cancer compared to European Americans (EA). miRNAs play a critical role in these tumors, leading to tumor progression. In this study, we investigated the role of miR-182 in racial disparity in prostate cancer.

Results

We found significantly increased levels of miR-182 in prostate cancer tissues compared to BPH. Also, miR-182 shows increased expression in AA prostate cancer cell line and tissue samples compared to EA. We performed biochemical recurrence (BCR) - free survival time in AA and EA patients and found that high miR-182 expression had significantly shorter BCR-free survival than patients with low miR-182 expression (P = 0.031). To elucidate the role of miR-182, we knocked down miR-182 in EA (DU-145 and LNCaP) and AA (MDA-PCa-2b) cell lines and found an increase in apoptosis, arrest of the cell cycle, and inhibition of colony formation in the AA cell line to a greater extent than EA cell lines.

Conclusions

Our results showed that PDCD4 is a direct miR-182 target and its inhibition is associated with aggressiveness and high Gleason grade in prostate cancer among AA. These findings show that miR-182 is highly expressed in AA patients and miR-182 may be a target for effective therapy in AA patients.

Available only for authorised users

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. https://doi.org/10.3322/caac.21590.CrossRefPubMed

Neslund-Dudas CM, McBride RB, Kandegedara A, Rybicki BA, Kryvenko ON, Chitale D, et al. Association between cadmium and androgen receptor protein expression differs in prostate tumors of African American and European American men. J Trace Elem Med Biol. 2018;48:233–8. https://doi.org/10.1016/j.jtemb.2018.04.006.CrossRefPubMedPubMedCentral

Akinyemiju T, Wiener H, Pisu M. Cancer-related risk factors and incidence of major cancers by race, gender and region; analysis of the NIH-AARP diet and health study. BMC Cancer. 2017;17(1):597. https://doi.org/10.1186/s12885-017-3557-1.CrossRefPubMedPubMedCentral

McGinley KF, Tay KJ, Moul JW. Prostate cancer in men of African origin. Nat Rev Urol. 2016;13(2):99–107. https://doi.org/10.1038/nrurol.2015.298.CrossRefPubMed

Bhardwaj A, Srivastava SK, Khan MA, Prajapati VK, Singh S, Carter JE, Singh AP. Racial disparities in prostate cancer: a molecular perspective. 2017;22:772–82. https://doi.org/10.2741/4515.CrossRef

Pinheiro PS, Medina H, Callahan KE, Kwon D, Ragin C, Sherman R, et al. Cancer mortality among US blacks: variability between African Americans, afro-Caribbeans, and Africans. Cancer Epidemiol. 2020;66:101709. https://doi.org/10.1016/j.canep.2020.101709.CrossRefPubMedPubMedCentral

Santos PB, Patel H, Henrique R, Félix A. Can epigenetic and inflammatory biomarkers identify clinically aggressive prostate cancer? World J Clin Oncol. 2020;11(2):43–52. https://doi.org/10.5306/wjco.v11.i2.43.CrossRefPubMedPubMedCentral

Bottani M, Banfi G, Lombardi G. Circulating miRNAs as diagnostic and prognostic biomarkers in common solid tumors: focus on lung, breast, prostate cancers, and osteosarcoma. J Clin Med. 2019;8(10):1661.CrossRef

Borkowska EM, Konecki T, Pietrusiński M, Borowiec M, Jabłonowski Z. MicroRNAs which can prognosticate aggressiveness of bladder cancer. Cancers (Basel). 2019;11(10):1551.CrossRef

10.

Lim MCJ, Baird AM, Aird J, Greene J, Kapoor D, Gray SG, et al. RNAs as candidate diagnostic and prognostic markers of prostate cancer-from cell line models to liquid biopsies. Diagnostics (Basel). 2018;8(3):60.CrossRef

11.

Regouc M, Belge G, Lorch A, Dieckmann KP, Pichler M. Non-coding microRNAs as novel potential tumor markers in testicular cancer. Cancers (Basel). 2020;12(3):749.CrossRef

12.

Wei Q, Lei R, Hu G. Roles of miR-182 in sensory organ development and cancer. Thorac Cancer. 2015;6(1):2–9. https://doi.org/10.1111/1759-7714.12164.CrossRefPubMedPubMedCentral

13.

Wang F, Zhong S, Zhang H, Zhang W, Zhang H, Wu X, et al. Prognostic value of microRNA-182 in cancers: a meta-analysis. Dis Markers. 2015;2015:482146.PubMedPubMedCentral

14.

Kurul NO, Ates F, Yilmaz I, Narli G, Yesildal C, Senkul T. The association of let-7c, miR-21, miR-145, miR-182, and miR-221 with clinicopathologic parameters of prostate cancer in patients diagnosed with low-risk disease. Prostate. 2019;79(10):1125–32. https://doi.org/10.1002/pros.23825.CrossRefPubMed

15.

Yao XG, Tan Q, Liu PP, Feng LJ. Tissue microRNA-182 expression level and its potential prognostic value for papillary thyroid carcinoma. Int J Clin Exp Pathol. 2019;12(8):3128–33.PubMedPubMedCentral

16.

Shibahara K, Asano M, Ishida Y, Aoki T, Koike T, Honjo T. Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death. Gene. 1995;166(2):297–301. https://doi.org/10.1016/0378-1119(95)00607-9.CrossRefPubMed

17.

Wang Q, Yang HS. The role of Pdcd4 in tumour suppression and protein translation. Biol Cell. 2018;110(8):169–77. https://doi.org/10.1111/boc.201800014.CrossRef

18.

Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH, Sherman NE, Pagano M. S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science. 2006;314(5798):467–71. https://doi.org/10.1126/science.1130276.CrossRefPubMed

19.

Palamarchuk A, Efanov A, Maximov V, Aqeilan RI, Croce CM, Pekarsky Y. Akt phosphorylates and regulates Pdcd4 tumor suppressor protein. Cancer Res. 2005;65(24):11282–6. https://doi.org/10.1158/0008-5472.CAN-05-3469.CrossRefPubMed

20.

Mens MMJ, Ghanbari M. Cell cycle regulation of stem cells by microRNAs. Stem Cell Rev Rep. 2018;14(3):309–22. https://doi.org/10.1007/s12015-018-9808-y.CrossRefPubMed

21.

Motoyama K, Inoue H, Mimori K, Tanaka F, Kojima K, Uetake H, et al. Clinicopathological and prognostic significance of PDCD4 and microRNA-21 in human gastric cancer. Int J Oncol. 2010;36(5):1089–95. https://doi.org/10.3892/ijo_00000590.CrossRefPubMed

22.

Liu Y, Sun H, Mao H, Gao M, Tan X, Li Y, et al. Expression of tumor suppressor programmed cell death 4 in endometrioid endometrial carcinomas and clinicopathological significance. Oncol Lett. 2018;15(6):9369–76. https://doi.org/10.3892/ol.2018.8517.CrossRefPubMedPubMedCentral

23.

Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66. https://doi.org/10.1038/nrc1997.CrossRefPubMed

24.

DePrimo SE, Diehn M, Nelson JB, Reiter RE, Matese J, Fero M, et al. Transcriptional programs activated by exposure of human prostate cancer cells to androgen. Genome Biol. 2002;3(7):RESEARCH0032.CrossRef

25.

Suh SO, Chen Y, Zaman MS, Hirata H, Yamamura S, Shahryari V, et al. MicroRNA-145 is regulated by DNA methylation and p53 gene mutation in prostate cancer. Carcinogenesis. 2011;32(5):772–8. https://doi.org/10.1093/carcin/bgr036.CrossRefPubMedPubMedCentral

26.

Shiina M, Hashimoto Y, Kato T, Yamamura S, Tanaka Y, Majid S, et al. Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians. Oncotarget. 2017;8(5):8356–68. https://doi.org/10.18632/oncotarget.14198.CrossRefPubMed

27.

Hashimoto Y, Shiina M, Dasgupta P, Kulkarni P, Kato T, Wong RK, et al. Upregulation of miR-130b contributes to risk of poor prognosis and racial disparity in African-American prostate cancer. Cancer Prev Res (Phila). 2019;12(9):585–98. https://doi.org/10.1158/1940-6207.CAPR-18-0509.CrossRef

28.

Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8. https://doi.org/10.1038/bmt.2012.244.CrossRefPubMed

29.

Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: prostate and bladder tumours. Eur Urol. 2016;70(1):106–19. https://doi.org/10.1016/j.eururo.2016.02.028.CrossRefPubMed

30.

Li Y, Li L. Prognostic values and prospective pathway signaling of MicroRNA-182 in ovarian cancer: a study based on gene expression omnibus (GEO) and bioinformatics analysis. J Ovarian Res. 2019;12(1):106. https://doi.org/10.1186/s13048-019-0580-7.CrossRefPubMedPubMedCentral

31.

Peterson SM, Thompson JA, Ufkin ML, Sathyanarayana P, Liaw L, Congdon CB. Common features of microRNA target prediction tools. Front Genet. 2014;5:23.CrossRef

32.

Yuan J, Kensler KH, Hu Z, Zhang Y, Zhang T, Jiang J, et al. Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry. PLoS Genet. 2020;16(2):e1008641. https://doi.org/10.1371/journal.pgen.1008641.CrossRefPubMedPubMedCentral

33.

Massillo C, Dalton GN, Farre PL, De Luca P, De Siervi A. Implications of microRNA dysregulation in the development of prostate cancer. Reproduction. 2017;154(4):R81–97. https://doi.org/10.1530/REP-17-0322.CrossRefPubMed

34.

Song CJ, Chen H, Chen LZ, Ru GM, Guo JJ, Ding QN. The potential of microRNAs as human prostate cancer biomarkers: a meta-analysis of related studies. J Cell Biochem. 2018;119(3):2763–86. https://doi.org/10.1002/jcb.26445.CrossRefPubMed

35.

Hashimoto Y, Shiina M, Kato T, Yamamura S, Tanaka Y, Majid S, et al. The role of miR-24 as a race related genetic factor in prostate cancer. Oncotarget. 2017;8(10):16581–93. https://doi.org/10.18632/oncotarget.15016.CrossRefPubMedPubMedCentral

36.

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. https://doi.org/10.1074/jbc.M109.031427.CrossRefPubMedPubMedCentral

37.

Li G, Li M, Hu J, Lei R, Xiong H, Ji H, et al. The microRNA-182-PDK4 axis regulates lung tumorigenesis by modulating pyruvate dehydrogenase and lipogenesis. Oncogene. 2017;36(7):989–98. https://doi.org/10.1038/onc.2016.265.CrossRefPubMed

38.

Xue J, Zhou A, Wu Y, Morris SA, Lin K, Amin S, et al. miR-182-5p induced by STAT3 activation promotes glioma tumorigenesis. Cancer Res. 2016;76(14):4293–304. https://doi.org/10.1158/0008-5472.CAN-15-3073.CrossRefPubMedPubMedCentral

39.

Deng JL, Zhang HB, Zeng Y, Xu YH, Huang Y, Wang G. Effects of CORO2A on cell migration and proliferation and its potential regulatory network in breast cancer. Front Oncol. 2020;10:916. https://doi.org/10.3389/fonc.2020.00916.CrossRefPubMedPubMedCentral

40.

Ryl T, Kuchen EE, Bell E, Shao C, Flórez AF, Mönke G, et al. Cell-cycle position of single MYC-driven cancer cells dictates their susceptibility to a chemotherapeutic drug. Cell Syst. 2017;5(3):237–50.e8.CrossRef

41.

Yu J, Lei R, Zhuang X, Li X, Li G, Lev S, et al. MicroRNA-182 targets SMAD7 to potentiate TGFbeta-induced epithelial-mesenchymal transition and metastasis of cancer cells. Nat Commun. 2016;7(1):13884. https://doi.org/10.1038/ncomms13884.CrossRefPubMedPubMedCentral

42.

Cmarik JL, Min H, Hegamyer G, Zhan S, Kulesz-Martin M, Yoshinaga H, et al. Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation. Proc Natl Acad Sci U S A. 1999;96(24):14037–42. https://doi.org/10.1073/pnas.96.24.14037.CrossRefPubMedPubMedCentral

43.

Yoshinaga H, Matsuhashi S, Fujiyama C, Masaki Z. Novel human PDCD4 (H731) gene expressed in proliferative cells is expressed in the small duct epithelial cells of the breast as revealed by an anti-H731 antibody. Pathol Int. 1999;49(12):1067–77. https://doi.org/10.1046/j.1440-1827.1999.00995.x.CrossRefPubMed

44.

Ning FL, Wang F, Li ML, Yu ZS, Hao YZ, Chen SS. MicroRNA-182 modulates chemosensitivity of human non-small cell lung cancer to cisplatin by targeting PDCD4. Diagn Pathol. 2014;9:143.CrossRef

45.

Lu YY, Zheng JY, Liu J, Huang CL, Zhang W, Zeng Y. miR-183 induces cell proliferation, migration, and invasion by regulating PDCD4 expression in the SW1990 pancreatic cancer cell line. Biomed Pharmacother. 2015;70:151–7. https://doi.org/10.1016/j.biopha.2015.01.016.CrossRefPubMed

46.

Zhang J, Ma L, Shi D, Zhang Z, Yao C, Zhao X, et al. Prognostic significance of miR-21 and PDCD4 in patients with stage II esophageal carcinoma after surgical resection. J Cell Biochem. 2018;119(6):4783–91. https://doi.org/10.1002/jcb.26672.CrossRefPubMed

47.

Hanna J, Hossain GS, Kocerha J. The potential for microRNA therapeutics and clinical research. Front Genet. 2019;10:478. https://doi.org/10.3389/fgene.2019.00478.CrossRefPubMedPubMedCentral

48.

Ma G, Tang M, Wu Y, Xu X, Pan F, Xu R. LncRNAs and miRNAs: potential biomarkers and therapeutic targets for prostate cancer. Am J Transl Res. 2016;8(12):5141–50.PubMedPubMedCentral

49.

Slack FJ, Chinnaiyan AM. The role of non-coding RNAs in oncology. Cell. 2019;179(5):1033–55. https://doi.org/10.1016/j.cell.2019.10.017.CrossRefPubMedPubMedCentral

50.

Bahrami A, Aledavood A, Anvari K, Hassanian SM, Maftouh M, Yaghobzade A, et al. The prognostic and therapeutic application of microRNAs in breast cancer: tissue and circulating microRNAs. J Cell Physiol. 2018;233(2):774–86. https://doi.org/10.1002/jcp.25813.CrossRefPubMed

51.

Hassanein M, Callison JC, Callaway-Lane C, Aldrich MC, Grogan EL, Massion PP. The state of molecular biomarkers for the early detection of lung cancer. Cancer Prev Res (Phila). 2012;5(8):992–1006. https://doi.org/10.1158/1940-6207.CAPR-11-0441.CrossRef

52.

Crawford ED, Heidenreich A, Lawrentschuk N, Tombal B, Pompeo ACL, Mendoza-Valdes A, et al. Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations. Prostate Cancer Prostatic Dis. 2019;22(1):24–38. https://doi.org/10.1038/s41391-018-0079-0.CrossRefPubMed

Title: Role of miR-182/PDCD4 axis in aggressive behavior of prostate cancer in the African Americans
Authors: Marisa Shiina
Yutaka Hashimoto
Priyanka Kulkarni
Pritha Dasgupta
Varahram Shahryari
Soichiro Yamamura
Yuichiro Tanaka
Rajvir Dahiya
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Prostate Cancer
Prostate Cancer
Benign Prostatic Hypertrophy
Benign Prostatic Hypertrophy
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08723-6

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Image Credits

ASCO 2024 | Highlights of the Day: Breast cancer – metastatic/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Gynecologic Cancer/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Breast Cancer – local/regional/adjuvant/© 2024 American Society of Clinical Oncology, all rights reserved., Melanoma/© selvanegra / Getty Images / iStock, Antibody drug conjugated with cytotoxic payload/© Love Employee / Getty images / iStock

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Vasculogenic mimicry, a negative indicator for progression free survival of lung adenocarcinoma irrespective of first line treatment and epithelial growth factor receptor mutation status

Pressurized intra-peritoneal aerosol chemotherapy (PIPAC): increased intraperitoneal pressure does not affect distribution patterns but leads to deeper penetration depth of doxorubicin in a sheep model

High vimentin expression with E-cadherin expression loss predicts a poor prognosis after resection of grade 1 and 2 pancreatic neuroendocrine tumors

The contribution of Lynch syndrome to early onset malignancy in Ireland

Poor prognosis of male triple-positive breast Cancer patients: a propensity score matched SEER analysis and molecular portraits