MiR-27a Modulates Radiosensitivity of Triple-negative Breast Cancer (TNBC) Cells by Targeting CDC27

Overview

Journal Med Sci Monit

Specialties General Medicine
Pathology

Date 2015 May 7

PMID 25943633

Citations 38

Authors

Yong-Qiang Ren

Fengkui Fu

Jianjun Han

Affiliations

Soon will be listed here.

Abstract

Background: MiR-27a is significantly overexpressed in triple-negative breast cancer (TNBC). However, the exact biological function of MiR-27a in TNBC is not fully understood. In this study, we verified miR-27a expression in TNBC cells and explored how its overexpression modulates radiosensitivity of the cells.

Material/methods: qRT-PCR analysis was performed to study miR-27a expression in TNBC lines MDA-MB-435 and MDA-MB-231 and in normal human breast epithelial cell line MCF10A. Dual luciferase assay was performed to verify a putative downstream target of miR-27a, CDC27. CCK-8 assay was used to assess the influence of miR-27a-CDC27 axis on cell proliferation under irradiation (IR) treatment.

Results: We confirmed significantly higher miR-27a expression in 2 TNBC cell lines--MDA-MB-435 and MDA-MB-231--than in human breast epithelial cell line MCF10A. miR-27a could modulate proliferation and radiosensitivity of TNBC cells. CDC-27 is a direct target of miR-27a and its downregulation conferred increased radioresistance of the cells.

Conclusions: The miR-27a-CDC27 axis might play an important role in modulating response to radiotherapy in TNBC cells. Testing miR-27a expression might be a useful way to identify a subgroup of patients who will benefit from an IR-based therapeutic approach.

Citing Articles

Identification of key genes underlying radiosensitivity and radioresistance in endometrial cancer through integrated bioinformatics analysis.

Wan C, Zhang L, Yu T, Lu H, Xiao H, Du J Front Genet. 2025; 16:1469610.

PMID: 39926275 PMC: 11802559. DOI: 10.3389/fgene.2025.1469610.

Non-coding RNAs modulation in breast cancer radioresponse: mechanisms and therapeutic implications.

Moqadami A, Ghafari S, Khalaj-Kondori M Strahlenther Onkol. 2024; .

PMID: 39545960 DOI: 10.1007/s00066-024-02317-4.

Non-coding RNAs as modulators of radioresponse in triple-negative breast cancer: a systematic review.

Tofolo M, Berti F, Nunes-Souza E, Ruthes M, Berti L, Fonseca A J Biomed Sci. 2024; 31(1):93.

PMID: 39354523 PMC: 11445946. DOI: 10.1186/s12929-024-01081-y.

Research progress on factors affecting the sensitivity of breast cancer to radiotherapy: a narrative review.

Zhang Q, Qian F, Cai M, Liu R, Chen M, Li Z Transl Cancer Res. 2024; 13(7):3869-3888.

PMID: 39145054 PMC: 11319974. DOI: 10.21037/tcr-24-71.

Molecular subtypes of breast cancer predicting clinical benefits of radiotherapy after breast-conserving surgery: a propensity-score-matched cohort study.

Hung S, Yang H, Lee M, Liu D, Chen L, Chew C Breast Cancer Res. 2023; 25(1):149.

PMID: 38066611 PMC: 10709935. DOI: 10.1186/s13058-023-01747-9.

References

Bartel D . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. View

Talvinen K, Karra H, Pitkanen R, Ahonen I, Nykanen M, Lintunen M . Low cdc27 and high securin expression predict short survival for breast cancer patients. APMIS. 2013; 121(10):945-53. DOI: 10.1111/apm.12110. View

Mertens-Talcott S, Chintharlapalli S, Li X, Safe S . The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. Cancer Res. 2007; 67(22):11001-11. DOI: 10.1158/0008-5472.CAN-07-2416. View

Guttilla I, White B . Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. J Biol Chem. 2009; 284(35):23204-16. PMC: 2749094. DOI: 10.1074/jbc.M109.031427. View

Foulkes W, Smith I, Reis-Filho J . Triple-negative breast cancer. N Engl J Med. 2010; 363(20):1938-48. DOI: 10.1056/NEJMra1001389. View

Stevens K, Wang X, Fredericksen Z, Pankratz V, Cerhan J, Vachon C . Evaluation of associations between common variation in mitotic regulatory pathways and risk of overall and high grade breast cancer. Breast Cancer Res Treat. 2011; 129(2):617-22. PMC: 3508696. DOI: 10.1007/s10549-011-1587-y. View

Singh N, Wiltshire T, Thompson J, Mer G, Couch F . Molecular basis for the association of microcephalin (MCPH1) protein with the cell division cycle protein 27 (Cdc27) subunit of the anaphase-promoting complex. J Biol Chem. 2011; 287(4):2854-62. PMC: 3268443. DOI: 10.1074/jbc.M111.307868. View

Lee S, Langhans S . Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis. BMC Cancer. 2012; 12:44. PMC: 3296673. DOI: 10.1186/1471-2407-12-44. View

Ha G, Roth A, Lai D, Bashashati A, Ding J, Goya R . Integrative analysis of genome-wide loss of heterozygosity and monoallelic expression at nucleotide resolution reveals disrupted pathways in triple-negative breast cancer. Genome Res. 2012; 22(10):1995-2007. PMC: 3460194. DOI: 10.1101/gr.137570.112. View

10.

Tang W, Zhu J, Su S, Wu W, Liu Q, Su F . MiR-27 as a prognostic marker for breast cancer progression and patient survival. PLoS One. 2012; 7(12):e51702. PMC: 3519894. DOI: 10.1371/journal.pone.0051702. View

11.

Korner C, Keklikoglou I, Bender C, Worner A, Munstermann E, Wiemann S . MicroRNA-31 sensitizes human breast cells to apoptosis by direct targeting of protein kinase C epsilon (PKCepsilon). J Biol Chem. 2013; 288(12):8750-8761. PMC: 3605692. DOI: 10.1074/jbc.M112.414128. View

12.

Rajkumar T, Gopal G, Selvaluxmi G, Rajalekshmy K . CDC27 protein is involved in radiation response in squamous cell cervix carcinoma. Indian J Biochem Biophys. 2013; 42(5):271-8. View

13.

Yahya S, Elsayed G . A summary for molecular regulations of miRNAs in breast cancer. Clin Biochem. 2014; 48(6):388-96. DOI: 10.1016/j.clinbiochem.2014.12.013. View

14.

Yang L, Perez A, Fujie S, Warden C, Li J, Wang Y . Wnt modulates MCL1 to control cell survival in triple negative breast cancer. BMC Cancer. 2014; 14:124. PMC: 3936852. DOI: 10.1186/1471-2407-14-124. View

15.

Gasparini P, Lovat F, Fassan M, Casadei L, Cascione L, Jacob N . Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation. Proc Natl Acad Sci U S A. 2014; 111(12):4536-41. PMC: 3970505. DOI: 10.1073/pnas.1402604111. View

16.

Tang W, Yu F, Yao H, Cui X, Jiao Y, Lin L . miR-27a regulates endothelial differentiation of breast cancer stem like cells. Oncogene. 2013; 33(20):2629-38. DOI: 10.1038/onc.2013.214. View

17.

Gasparini P, Cascione L, Fassan M, Lovat F, Guler G, Balci S . microRNA expression profiling identifies a four microRNA signature as a novel diagnostic and prognostic biomarker in triple negative breast cancers. Oncotarget. 2014; 5(5):1174-84. PMC: 4012726. DOI: 10.18632/oncotarget.1682. View

18.

Min W, Wang B, Li J, Han J, Zhao Y, Su W . The expression and significance of five types of miRNAs in breast cancer. Med Sci Monit Basic Res. 2014; 20:97-104. PMC: 4117676. DOI: 10.12659/MSMBR.891246. View

19.

Chang L, Zhang Z, Yang J, McLaughlin S, Barford D . Molecular architecture and mechanism of the anaphase-promoting complex. Nature. 2014; 513(7518):388-393. PMC: 4456660. DOI: 10.1038/nature13543. View

20.

Thornton B, Ng T, Matyskiela M, Carroll C, Morgan D, Toczyski D . An architectural map of the anaphase-promoting complex. Genes Dev. 2006; 20(4):449-60. PMC: 1369047. DOI: 10.1101/gad.1396906. View