We aimed to explore the potential application of circulating microRNA-451 (miR-451) in serum in predicting the resistance to neoadjuvant chemotherapy (NACT) in breast cancer (BC).
METHODS:
Eighty-two BC patients who underwent NACT were recruited in our study, including 41 NACT-sensitive patients (NACT-sensitive group) and 41 NACT-resistant patients (NACT-resistant group). Additionally, 60 healthy subjects were selected as normal controls. Epirubicin-resistant MCF-7 BC cell line (MCF-7/EPI) and docetaxel-resistant MCF-7 BC cell line(MCF-7/DOC) were cultured in our study. MTT assay was applied to calculate the survival rates of MCF-7 cells, MCF-7/DOC cells and MCF-7/EPI cells. The expression levels of miR-451 in normal controls, NACT-sensitive group, NACT-resistant group, MCF-7 cells, MCF-7/DOC cells and MCF-7/EPI cells were measured by qRT-PCR method.
RESULTS:
The proliferation rates of both the MCF-7/DOC and MCF-7/EPI cells were significantly restrained at the drug concentration of 10 ng/ml, 50 ng/ml, 100 ng/ml and 200 ng/ml. However, the proliferation rates of MCF-7/DOC and MCF-7/EPI cells both increased significantly at the drug concentration of 500ng/ml. Furthermore, the IC50 of MCF-7/DOC cells was 23.603 ng/ml and the IC50 of MCF-7/EPI cells was 3.209 ng/ml. The relative expression of miR-451 was significantly lower in both the NACT-resistant group and the NACT-sensitive group than the normal control group. We also found that the relative expression level of miR-451 was significantly lower in the NACT-resistant group than that in the NACT-sensitive group. The expression of miR-451 in the MCF-7/EPI and the MCF-7/DOC cell lines was significantly lower than that in the MCF-7 cell lines.
CONCLUSION:
We supported the view that the relative expression level of miR-451 was lower in the NACT-resistant BC patients, suggesting the circulating miR-451 may have a functional significance in predicting the resistance to NACT in BC patients. We laid a foundation for further research on the resistance to NACT in BC treatment.
TeertstraH.J., LooC.E., van den BoschM.A., van TinterenH., RutgersE.J., MullerS.H. and GilhuijsK.G., Breast tomosynthesis in clinical practice: initial results, Eur Radiol20 (2010), 16-24.
2.
TangX., Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer, Cancer Lett332 (2013), 3-10.
3.
MukhtarR.A., NseyoO., CampbellM.J. and EssermanL.J., Tumor-associated macrophages in breast cancer as potential biomarkers for new treatments and diagnostics, Expert Rev Mol Diagn11 (2011), 91-100.
4.
SiegelR., NaishadhamD. and JemalA., Cancer statistics, 2013, CA Cancer J Clin63 (2013), 11-30.
5.
ZhengW., LongJ., GaoY.T., LiC., ZhengY., XiangY.B., WenW., LevyS., DemingS.L., HainesJ.L., GuK., FairA.M., CaiQ., LuW. and ShuX.O., Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1, Nat Genet41 (2009), 324-8.
6.
Early Breast Cancer Trialists' CollaborativeG., DaviesC., GodwinJ., GrayR., ClarkeM., CutterD., DarbyS., McGaleP., PanH.C., TaylorC., WangY.C., DowsettM., IngleJ. and PetoR., Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: Patient-level meta-analysis of randomised trials, Lancet378 (2011), 771-84.
7.
MunsterP.N., MooreA.P., Ismail-KhanR., CoxC.E., LacevicM., Gross-KingM., XuP., CarterW.B. and MintonS.E., Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer, J Clin Oncol30 (2012), 533-8.
8.
AssiH.A., KhouryK.E., DboukH., KhalilL.E., MouhieddineT.H. and El SaghirN.S., Epidemiology and prognosis of breast cancer in young women, J Thorac Dis5 Suppl 1 (2013), S2-8.
9.
ToleutayU., ReznikV., KalmatayevaZ. and SmigelskasK., Risk factors of breast cancer in kyzylorda oblast of Kazakhstan: a case-control study, Asian Pac J Cancer Prev14 (2013), 5961-4.
10.
EndogenousH., Breast Cancer CollaborativeG., KeyT.J., ApplebyP.N., ReevesG.K., RoddamA.W., HelzlsouerK.J., AlbergA.J., RollisonD.E., DorganJ.F., BrintonL.A., OvervadK., KaaksR., TrichopoulouA., Clavel-ChapelonF., PanicoS., DuellE.J., PeetersP.H., RinaldiS., FentimanI.S., DowsettM., ManjerJ., LennerP., HallmansG., BagliettoL., EnglishD.R., GilesG.G., HopperJ.L., SeveriG., MorrisH.A., HankinsonS.E., TworogerS.S., KoenigK., Zeleniuch-JacquotteA., ArslanA.A., TonioloP., ShoreR.E., KroghV., MicheliA., BerrinoF., Barrett-ConnorE., LaughlinG.A., KabutoM., AkibaS., StevensR.G., NeriishiK., LandC.E., CauleyJ.A., LuiL.Y., CummingsS.R., GunterM.J., RohanT.E. and StricklerH.D., Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies, Br J Cancer105 (2011), 709-22.
11.
SwerdlowA.J., JonesM.E., SchoemakerM.J., HemmingJ., ThomasD., WilliamsonJ. and AshworthA., The Breakthrough Generations Study: Design of a long-term UK cohort study to investigate breast cancer aetiology, Br J Cancer105 (2011), 911-7.
12.
LoS.S., MumbyP.B., NortonJ., RychlikK., SmerageJ., KashJ., ChewH.K., GaynorE.R., HayesD.F., EpsteinA. and AlbainK.S., Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection, J Clin Oncol28 (2010), 1671-6.
13.
RidnerS.H., DietrichM.S. and KiddN., Breast cancer treatment-related lymphedema self-care: education, practices, symptoms, and quality of life, Support Care Cancer19 (2011), 631-7.
14.
von MinckwitzG., UntchM., BlohmerJ.U., CostaS.D., EidtmannH., FaschingP.A., GerberB., EiermannW., HilfrichJ., HuoberJ., JackischC., KaufmannM., KonecnyG.E., DenkertC., NekljudovaV., MehtaK. and LoiblS., Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes, J Clin Oncol30 (2012), 1796-804.
15.
BearH.D., TangG., RastogiP., Geyer, Jr.C.E., RobidouxA., AtkinsJ.N., Baez-DiazL., BrufskyA.M., MehtaR.S., FehrenbacherL., YoungJ.A., SenecalF.M., GaurR., MargoleseR.G., AdamsP.T., GrossH.M., CostantinoJ.P., SwainS.M., MamounasE.P. and WolmarkN., Bevacizumab added to neoadjuvant chemotherapy for breast cancer, N Engl J Med366 (2012), 310-20.
16.
KaufmannM., von MinckwitzG., MamounasE.P., CameronD., CareyL.A., CristofanilliM., DenkertC., EiermannW., GnantM., HarrisJ.R., KarnT., LiedtkeC., MauriD., RouzierR., RuckhaeberleE., SemiglazovV., SymmansW.F., TuttA. and PusztaiL., Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer, Ann Surg Oncol19 (2012), 1508-16.
17.
WangW., KwonE.J. and TsaiL.H., MicroRNAs in learning, memory, and neurological diseases, Learn Mem19 (2012), 359-68.
18.
GrossoS., DoyenJ., ParksS.K., BerteroT., PayeA., CardinaudB., GounonP., Lacas-GervaisS., NoelA., PouyssegurJ., BarbryP., MazureN.M. and MariB., MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines, Cell Death Dis4 (2013), e544.
19.
CipolliniM., LandiS. and GemignaniF., MicroRNA binding site polymorphisms as biomarkers in cancer management and research, Pharmgenomics Pers Med7 (2014), 173-91.
20.
Moyret-LalleC., RuizE. and PuisieuxA., Epithelial-mesenchymal transition transcription factors and miRNAs: ``Plastic surgeons'' of breast cancer, World J Clin Oncol5 (2014), 311-22.
21.
ZhangW., ZhangC., ChenH., LiL., TuY., LiuC., ShiS., ZenK. and LiuZ., Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS, Clin J Am Soc Nephrol9 (2014), 1545-52.
22.
GyparakiM.T., BasdraE.K. and PapavassiliouA.G., MicroRNAs as regulatory elements in triple negative breast cancer, Cancer Lett354 (2014), 1-4.
23.
OomA.L., HumphriesB.A. and YangC., MicroRNAs: novel players in cancer diagnosis and therapies, Biomed Res Int2014 (2014), 959461.
24.
LiH.Y., ZhangY., CaiJ.H. and BianH.L., MicroRNA-451 inhibits growth of human colorectal carcinoma cells via downregulation of Pi3k/Akt pathway, Asian Pac J Cancer Prev14 (2013), 3631-4.
25.
DengB., MolinaJ., AubryM.C., SunZ., WangL., EckloffB.W., VasmatzisG., YouM., WiebenE.D., JenJ., WigleD.A. and YangP., Clinical biomarkers of pulmonary carcinoid tumors in never smokers via profiling miRNA and target mRNA, Cell Biosci4 (2014), 35.
26.
RocciA., HofmeisterC.C. and PichiorriF., The potential of miRNAs as biomarkers for multiple myeloma, Expert Rev Mol Diagn (2014), 1-13.
27.
DuanJ.H. and FangL., MicroRNA-92 promotes gastric cancer cell proliferation and invasion through targeting FXR, Tumour Biol (2014).
28.
HwangK.C., The Role of MicroRNAs in Vascular Diseases; Smooth Muscle Cell Differentiation and De-Differentiation, Korean Circ J44 (2014), 218-9.
29.
PanX., WangR. and WangZ.X., The potential role of miR-451 in cancer diagnosis, prognosis, and therapy, Mol Cancer Ther12 (2013), 1153-62.
30.
WangX.C., TianL.L., JiangX.Y., WangY.Y., LiD.G., SheY., ChangJ.H. and MengA.M., The expression and function of miRNA-451 in non-small cell lung cancer, Cancer Lett311 (2011), 203-9.
31.
TianY., NanY., HanL., ZhangA., WangG., JiaZ., HaoJ., PuP., ZhongY. and KangC., MicroRNA miR-451 downregulates the PI3K/AKT pathway through CAB39 in human glioma, Int J Oncol40 (2012), 1105-12.
32.
BitarteN., BandresE., BoniV., ZarateR., RodriguezJ., Gonzalez-HuarrizM., LopezI., Javier SolaJ., AlonsoM.M., FortesP. and Garcia-FoncillasJ., MicroRNA-451 is involved in the self-renewal, tumorigenicity, and chemoresistance of colorectal cancer stem cells, Stem Cells29 (2011), 1661-71.
33.
ChaiH., LiuM., TianR., LiX. and TangH., miR-20a targets BNIP2 and contributes chemotherapeutic resistance in colorectal adenocarcinoma SW480 and SW620 cell lines, Acta Biochim Biophys Sin (Shanghai)43 (2011), 217-25.
34.
KovalchukO., FilkowskiJ., MeservyJ., IlnytskyyY., TryndyakV.P., ChekhunV.F. and PogribnyI.P., Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin, Mol Cancer Ther7 (2008), 2152-9.
35.
WardA., BalwierzA., ZhangJ.D., KublbeckM., PawitanY., HielscherT., WiemannS. and SahinO., Re-expression of microRNA-375 reverses both tamoxifen resistance and accompanying EMT-like properties in breast cancer, Oncogene32 (2013), 1173-82.
36.
WangR., WangZ.X., YangJ.S., PanX., DeW. and ChenL.B., MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14), Oncogene30 (2011), 2644-58.
37.
NanY., HanL., ZhangA., WangG., JiaZ., YangY., YueX., PuP., ZhongY. and KangC., MiRNA-451 plays a role as tumor suppressor in human glioma cells, Brain Res1359 (2010), 14-21.
38.
BianchiF., NicassioF., MarziM., BelloniE., Dall'olioV., BernardL., PelosiG., MaisonneuveP., VeronesiG. and Di FioreP.P., A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer, EMBO Mol Med3 (2011), 495-503.
39.
SongJ., BaiZ., HanW., ZhangJ., MengH., BiJ., MaX., HanS. and ZhangZ., Identification of suitable reference genes for qPCR analysis of serum microRNA in gastric cancer patients, Dig Dis Sci57 (2012), 897-904.
40.
BianH.B., PanX., YangJ.S., WangZ.X. and DeW., Upregulation of microRNA-451 increases cisplatin sensitivity of non-small cell lung cancer cell line (A549), J Exp Clin Cancer Res30 (2011), 20.
41.
GanR., YangY., YangX., ZhaoL., LuJ. and MengQ.H., Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP3, Cancer Gene Ther21 (2014), 290-6.
Banzhaf-StrathmannJ. and EdbauerD., Good guy or bad guy: the opposing roles of microRNA 125b in cancer, Cell Commun Signal12 (2014), 30.
44.
MurrayM.Y., RushworthS.A., ZaitsevaL., BowlesK.M. and MacewanD.J., Attenuation of dexamethasone-induced cell death in multiple myeloma is mediated by miR-125b expression, Cell Cycle12 (2013), 2144-53.
45.
PogueA.I., CuiJ.G., LiY.Y., ZhaoY., CulicchiaF. and LukiwW.J., Micro RNA-125b (miRNA-125b) function in astrogliosis and glial cell proliferation, Neurosci Lett476 (2010), 18-22.
46.
ChenM.B., WeiM.X., HanJ.Y., WuX.Y., LiC., WangJ., ShenW. and LuP.H., MicroRNA-451 regulates AMPK/mTORC1 signaling and fascin1 expression in HT-29 colorectal cancer, Cell Signal26 (2014), 102-9.
47.
ZhuH.T., DongQ.Z., WangG., ZhouH.J., RenN., JiaH.L., YeQ.H. and QinL.X., Identification of suitable reference genes for qRT-PCR analysis of circulating microRNAs in hepatitis B virus-infected patients, Mol Biotechnol 50 (2012), 49-56.
48.
YuanJ., ChenL., ChenX., SunW. and ZhouX., Identification of serum microRNA-21 as a biomarker for chemosensitivity and prognosis in human osteosarcoma, J Int Med Res 40 (2012), 2090-7.
