Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Breast Cancer | Research article

miR-23b and miR-27b are oncogenic microRNAs in breast cancer: evidence from a CRISPR/Cas9 deletion study

Authors: Bethany N. Hannafon, Angela Cai, Cameron L. Calloway, Yi-Fan Xu, Roy Zhang, Kar-Ming Fung, Wei-Qun Ding

Published in: BMC Cancer | Issue 1/2019

Login to get access

Abstract

Background

Altered expression of microRNAs (miRNAs) is known to contribute to cancer progression. miR-23b and miR-27b, encoded within the same miRNA cluster, are reported to have both tumor suppressive and oncogenic activity across human cancers, including breast cancer.

Methods

To clarify this dichotomous role in breast cancer, miR-23b and miR-27b were knocked out using CRISPR/Cas9 gene knockout technology, and the role of endogenous miR-23b and miR-27b was examined in a breast cancer model system in vitro and in vivo.

Results

Characterization of the knockout cells in vitro demonstrated that miR-23b and miR-27b are indeed oncogenic miRNAs in MCF7 breast cancer cells. miR-23b and miR-27b knockout reduced tumor growth in xenograft nude mice fed a standard diet, supporting their oncogenic role in vivo. However, when xenograft mice were provided a fish-oil diet, miR-27b depletion, but not miR-23b depletion, compromised fish-oil-induced suppression of xenograft growth, indicating a context-dependent nature of miR-27b oncogenic activity.

Conclusions

Our results demonstrate that miR-23b and miR-27b are primarily oncogenic in MCF7 breast cancer cells and that miR-27b may have tumor suppressive activity under certain circumstances.
Literature
1.
Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433(7027):769–73.PubMedCrossRef
2.
Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS. Non-coding RNAs: regulators of disease. J Pathol. 2010;220(2):126–39.PubMedCrossRef
3.
Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006;34(Database issue):D140–4.PubMedCrossRef
4.
Panwar B, Omenn GS, Guan Y. miRmine: a database of human miRNA expression profiles. Bioinformatics. 2017;33(10):1554–60.PubMedPubMedCentral
5.
Chou CH, Chang NW, Shrestha S, Hsu SD, Lin YL, Lee WH, Yang CD, Hong HC, Wei TY, Tu SJ, et al. miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res. 2016;44(D1):D239–47.PubMedCrossRef
6.
He HC, Zhu JG, Chen XB, Chen SM, Han ZD, Dai QS, Ling XH, Fu X, Lin ZY, Deng YH, et al. MicroRNA-23b downregulates peroxiredoxin III in human prostate cancer. FEBS Lett. 2012;586(16):2451–8.PubMedCrossRef
7.
Majid S, Dar AA, Saini S, Arora S, Shahryari V, Zaman MS, Chang I, Yamamura S, Tanaka Y, Deng G, et al. miR-23b represses proto-oncogene Src kinase and functions as methylation-silenced tumor suppressor with diagnostic and prognostic significance in prostate cancer. Cancer Res. 2012;72(24):6435–46.PubMedPubMedCentralCrossRef
8.
Majid S, Dar AA, Saini S, Deng G, Chang I, Greene K, Tanaka Y, Dahiya R, Yamamura S. MicroRNA-23b functions as a tumor suppressor by regulating Zeb1 in bladder cancer. PLoS One. 2013;8(7):e67686.PubMedPubMedCentralCrossRef
9.
Chiyomaru T, Seki N, Inoguchi S, Ishihara T, Mataki H, Matsushita R, Goto Y, Nishikawa R, Tatarano S, Itesako T, et al. Dual regulation of receptor tyrosine kinase genes EGFR and c-met by the tumor-suppressive microRNA-23b/27b cluster in bladder cancer. Int J Oncol. 2015;46(2):487–96.PubMedCrossRef
10.
Pellegrino L, Stebbing J, Braga VM, Frampton AE, Jacob J, Buluwela L, Jiao LR, Periyasamy M, Madsen CD, Caley MP, et al. miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts. Nucleic Acids Res. 2013;41(10):5400–12.PubMedPubMedCentralCrossRef
11.
Ono M, Kosaka N, Tominaga N, Yoshioka Y, Takeshita F, Takahashi RU, Yoshida M, Tsuda H, Tamura K, Ochiya T. Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci Signal. 2014;7(332):ra63.PubMedCrossRef
12.
An Y, Zhang Z, Shang Y, Jiang X, Dong J, Yu P, Nie Y, Zhao Q. miR-23b-3p regulates the chemoresistance of gastric cancer cells by targeting ATG12 and HMGB2. Cell Death Dis. 2015;6:e1766.PubMedPubMedCentralCrossRef
13.
Huang TT, Ping YH, Wang AM, Ke CC, Fang WL, Huang KH, Lee HC, Chi CW, Yeh TS. The reciprocal regulation loop of Notch2 pathway and miR-23b in controlling gastric carcinogenesis. Oncotarget. 2015;6(20):18012–26.PubMedPubMedCentralCrossRef
14.
Zhang H, Hao Y, Yang J, Zhou Y, Li J, Yin S, Sun C, Ma M, Huang Y, Xi JJ. Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis. Nat Commun. 2011;2:554.PubMedCrossRef
15.
Geng J, Luo H, Pu Y, Zhou Z, Wu X, Xu W, Yang Z. Methylation mediated silencing of miR-23b expression and its role in glioma stem cells. Neurosci Lett. 2012;528(2):185–9.PubMedCrossRef
16.
Vaksman O, Trope C, Davidson B, Reich R. Exosome-derived miRNAs and ovarian carcinoma progression. Carcinogenesis. 2014;35(9):2113–20.PubMedCrossRef
17.
Tian L, Fang YX, Xue JL, Chen JZ. Four microRNAs promote prostate cell proliferation with regulation of PTEN and its downstream signals in vitro. PLoS One. 2013;8(9):e75885.PubMedPubMedCentralCrossRef
18.
Jin L, Wessely O, Marcusson EG, Ivan C, Calin GA, Alahari SK. Prooncogenic factors miR-23b and miR-27b are regulated by Her2/Neu, EGF, and TNF-alpha in breast cancer. Cancer Res. 2013;73(9):2884–96.PubMedCrossRef
19.
Qi P, Xu MD, Shen XH, Ni SJ, Huang D, Tan C, Weng WW, Sheng WQ, Zhou XY, Du X. Reciprocal repression between TUSC7 and miR-23b in gastric cancer. Int J Cancer. 2015;137(6):1269–78.PubMedCrossRef
20.
Chen L, Zhang K, Shi Z, Zhang A, Jia Z, Wang G, Pu P, Kang C, Han L. A lentivirus-mediated miR-23b sponge diminishes the malignant phenotype of glioma cells in vitro and in vivo. Oncol Rep. 2014;31(4):1573–80.PubMedCrossRef
21.
Chen L, Li H, Han L, Zhang K, Wang G, Wang Y, Liu Y, Zheng Y, Jiang T, Pu P, et al. Expression and function of miR-27b in human glioma. Oncol Rep. 2011;26(6):1617–21.PubMed
22.
Liu F, Zhang S, Zhao Z, Mao X, Huang J, Wu Z, Zheng L, Wang Q. MicroRNA-27b up-regulated by human papillomavirus 16 E7 promotes proliferation and suppresses apoptosis by targeting polo-like kinase2 in cervical cancer. Oncotarget. 2016;7(15):19666–79.PubMedPubMedCentral
23.
Wang Y, Rathinam R, Walch A, Alahari SK. ST14 (suppression of tumorigenicity 14) gene is a target for miR-27b, and the inhibitory effect of ST14 on cell growth is independent of miR-27b regulation. J Biol Chem. 2009;284(34):23094–106.PubMedPubMedCentralCrossRef
24.
Jiang J, Lv X, Fan L, Huang G, Zhan Y, Wang M, Lu H. MicroRNA-27b suppresses growth and invasion of NSCLC cells by targeting Sp1. Tumour Biol. 2014;35(10):10019–23.PubMedCrossRef
25.
Goto Y, Kojima S, Nishikawa R, Enokida H, Chiyomaru T, Kinoshita T, Nakagawa M, Naya Y, Ichikawa T, Seki N. The microRNA-23b/27b/24-1 cluster is a disease progression marker and tumor suppressor in prostate cancer. Oncotarget. 2014;5(17):7748–59.PubMedPubMedCentralCrossRef
26.
Ye J, Wu X, Wu D, Wu P, Ni C, Zhang Z, Chen Z, Qiu F, Xu J, Huang J. miRNA-27b targets vascular endothelial growth factor C to inhibit tumor progression and angiogenesis in colorectal cancer. PLoS One. 2013;8(4):e60687.PubMedPubMedCentralCrossRef
27.
Tao J, Zhi X, Zhang X, Fu M, Huang H, Fan Y, Guan W, Zou C. miR-27b-3p suppresses cell proliferation through targeting receptor tyrosine kinase like orphan receptor 1 in gastric cancer. J Exp Clin Cancer Res. 2015;34:139.PubMedPubMedCentralCrossRef
28.
Lin X, Chen L, Yao Y, Zhao R, Cui X, Chen J, Hou K, Zhang M, Su F, Chen J, et al. CCL18-mediated down-regulation of miR98 and miR27b promotes breast cancer metastasis. Oncotarget. 2015;6(24):20485–99.PubMedPubMedCentral
29.
Zhou Q, Gallagher R, Ufret-Vincenty R, Li X, Olson EN, Wang S. Regulation of angiogenesis and choroidal neovascularization by members of microRNA-23~27~24 clusters. Proc Natl Acad Sci U S A. 2011;108(20):8287–92.PubMedPubMedCentralCrossRef
30.
Urbich C, Kaluza D, Fromel T, Knau A, Bennewitz K, Boon RA, Bonauer A, Doebele C, Boeckel JN, Hergenreider E, et al. MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A. Blood. 2012;119(6):1607–16.PubMedCrossRef
31.
Wang KC, Garmire LX, Young A, Nguyen P, Trinh A, Subramaniam S, Wang N, Shyy JY, Li YS, Chien S. Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth. Proc Natl Acad Sci U S A. 2010;107(7):3234–9.PubMedPubMedCentralCrossRef
32.
Hannafon BN, Carpenter KJ, Berry WL, Janknecht R, Dooley WC, Ding WQ. Exosome-mediated microRNA signaling from breast cancer cells is altered by the anti-angiogenesis agent docosahexaenoic acid (DHA). Mol Cancer. 2015;14:133.PubMedPubMedCentralCrossRef
33.
Liu HT, Xing AY, Chen X, Ma RR, Wang YW, Shi DB, Zhang H, Li P, Chen HF, Li YH, et al. MicroRNA-27b, microRNA-101 and microRNA-128 inhibit angiogenesis by down-regulating vascular endothelial growth factor C expression in gastric cancers. Oncotarget. 2015;6(35):37458–70.PubMedPubMedCentral
34.
Ell B, Qiu Q, Wei Y, Mercatali L, Ibrahim T, Amadori D, Kang Y. The microRNA-23b/27b/24 cluster promotes breast cancer lung metastasis by targeting metastasis-suppressive gene prosaposin. J Biol Chem. 2014;289(32):21888–95.PubMedPubMedCentralCrossRef
35.
Zhu J, Zou Z, Nie P, Kou X, Wu B, Wang S, Song Z, He J. Downregulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression. Cell Death Dis. 2016;7(11):e2454.PubMedPubMedCentralCrossRef
36.
Ding L, Ni J, Yang F, Huang L, Deng H, Wu Y, Ding X, Tang J. Promising therapeutic role of miR-27b in tumor. Tumour Biol. 2017;39(3):1010428317691657.PubMed
37.
Stoll LL, Spector AA. Changes in serum influence the fatty acid composition of established cell lines. In Vitro. 1984;20(9):732–8.PubMedCrossRef
38.
Spector AA, Kiser RE, Denning GM, Koh SW, DeBault LE. Modification of the fatty acid composition of cultured human fibroblasts. J Lipid Res. 1979;20(4):536–47.PubMed
39.
Hannafon BN, Gin AL, Xu YF, Bruns M, Calloway CL, Ding WQ. Metastasis-associated protein 1 (MTA1) is transferred by exosomes and contributes to the regulation of hypoxia and estrogen signaling in breast cancer cells. Cell Commun Signal. 2019;17(1):13.PubMedPubMedCentralCrossRef
40.
41.
Lv M, Shen Y, Yang J, Li S, Wang B, Chen Z, Li P, Liu P, Yang J. Angiomotin family members: oncogenes or tumor suppressors? Int J Biol Sci. 2017;13(6):772–81.PubMedPubMedCentralCrossRef
42.
Helwak A, Kudla G, Dudnakova T, Tollervey D. Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell. 2013;153(3):654–65.PubMedPubMedCentralCrossRef
43.
Chen L, Han L, Zhang K, Shi Z, Zhang J, Zhang A, Wang Y, Song Y, Li Y, Jiang T, et al. VHL regulates the effects of miR-23b on glioma survival and invasion via suppression of HIF-1alpha/VEGF and beta-catenin/Tcf-4 signaling. Neuro-Oncology. 2012;14(8):1026–36.PubMedPubMedCentralCrossRef
44.
Zhang Z, Liu S, Shi R, Zhao G. miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition. Cancer Genet. 2011;204(9):486–91.PubMedCrossRef
45.
Jiao Y, Hannafon BN, Zhang RR, Fung KM, Ding WQ. Docosahexaenoic acid and disulfiram act in concert to kill cancer cells: a mutual enhancement of their anticancer actions. Oncotarget. 2017;8(11):17908–20.PubMedPubMedCentralCrossRef
46.
47.
Aquino-Jarquin G. Emerging role of CRISPR/Cas9 technology for MicroRNAs editing in cancer research. Cancer Res. 2017;77(24):6812–7.PubMedCrossRef
Metadata
Title
miR-23b and miR-27b are oncogenic microRNAs in breast cancer: evidence from a CRISPR/Cas9 deletion study
Authors
Bethany N. Hannafon
Angela Cai
Cameron L. Calloway
Yi-Fan Xu
Roy Zhang
Kar-Ming Fung
Wei-Qun Ding
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5839-2

Other articles of this Issue 1/2019

BMC Cancer 1/2019 Go to the issue

Research article

Tumor classification and biomarker discovery based on the 5’isomiR expression level

Research article

Clinical analysis of patients with skeletal metastasis of lung cancer

Research article

Damage to sebaceous gland and the efficacy of moisturizer after whole breast radiotherapy: a randomized controlled trial

Study protocol

Stereotactic ablative radiotherapy for the comprehensive treatment of 4–10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial

Research article

Surgical resection and reconstructive techniques using autologous femoral head bone-grafting in treating partial acetabular defects arising from primary pelvic malignant tumors

Research article

Clinicopathologic predictors of metastasis of different regional lymph nodes in patients intraoperatively diagnosed with stage-I non-small cell lung cancer
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