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BMC cancer
11 15, 2016;16 (1): 826.

miR-124-3p functions as a tumor suppressor in breast cancer by targeting CBL.

Yanbo Wang, Luxiao Chen, Zhenyu Wu, Minghai Wang, Fangfang Jin, Nan Wang, Xiuting Hu, Zhengya Liu, Chen-Yu Zhang, Ke Zen, Jiangning Chen, Hongwei Liang, Yujing Zhang, Xi Chen
Author Information
  1. Yanbo Wang: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
  2. Luxiao Chen: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
  3. Zhenyu Wu: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
  4. Minghai Wang: Department of General Surgery, The First Affiliated Yijishan Hospital with Wannan Medical College, 2 West Zheshan Road, Wuhu, Anhui, 241001, China.
  5. Fangfang Jin: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
  6. Nan Wang: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
  7. Xiuting Hu: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
  8. Zhengya Liu: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
  9. Chen-Yu Zhang: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
  10. Ke Zen: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
  11. Jiangning Chen: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China.
  12. Hongwei Liang: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China. lianghongwei0418@163.com.
  13. Yujing Zhang: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China. yjzhang@nju.edu.cn.
  14. Xi Chen: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu, 210046, China. xichen@nju.edu.cn.
PMID: 27842510 DOI: 10.1186/s12885-016-2862-4

Abstract

BACKGROUND: The origin and development of breast cancer remain complex and obscure. Recently, microRNA (miRNA) has been identified as an important regulator of the initiation and progression of breast cancer, and some studies have shown the essential role of miR-124-3p as a tumor suppressor in breast tumorigenesis. However, the detailed role of miR-124-3p in breast cancer remains poorly understood.
METHODS: Quantitative RT-PCR and western blotting assays were used to measure miR-124-3p and CBL expression levels in breast cancer tissues, respectively. Luciferase reporter assay was employed to validate the direct targeting of CBL by miR-124-3p. Cell proliferation and invasion assays were performed to analyze the biological functions of miR-124-3p and CBL in breast cancer cells.
RESULTS: In the present study, we found that miR-124-3p was consistently downregulated in breast cancer tissues. Moreover, we showed that miR-124-3p significantly suppressed the proliferation and invasion of breast cancer cells. In addition, we investigated the molecular mechanism through which miR-124-3p contributes to breast cancer tumorigenesis and identified CBL (Cbl proto-oncogene, E3 ubiquitin protein ligase) as a direct target gene of miR-124-3p. Moreover, we found that ectopic expression of CBL can attenuate the inhibitory effect of miR-124-3p on cell proliferation and invasion in breast cancer cells.
CONCLUSIONS: This study identified a new regulatory axis in which miR-124-3p and CBL regulate the proliferation and invasion of breast cancer cells.

Keywords

Breast cancer CBL Invasion Proliferation miR-124-3p

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MeSH Term

3' Untranslated Regions
Base Pairing
Breast Neoplasms
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Genes, Tumor Suppressor
Humans
MicroRNAs
Proto-Oncogene Mas
Proto-Oncogene Proteins c-cbl
RNA Interference
Reproducibility of Results

Chemicals

3' Untranslated Regions
MAS1 protein, human
MIRN124 microRNA, human
MicroRNAs
Proto-Oncogene Mas
Proto-Oncogene Proteins c-cbl
CBL protein, human
Journal Article
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0miR-124-3pbreastcancerCBLproliferationinvasioncellsidentifiedroletumorsuppressortumorigenesisassaysexpressiontissuesdirecttargetingfunctionsstudyfoundMoreoverBACKGROUND:origindevelopmentremaincomplexobscureRecentlymicroRNAmiRNAimportantregulatorinitiationprogressionstudiesshownessentialHoweverdetailedremainspoorlyunderstoodMETHODS:QuantitativeRT-PCRwesternblottingusedmeasurelevelsrespectivelyLuciferasereporterassayemployedvalidateCellperformedanalyzebiologicalRESULTS:presentconsistentlydownregulatedshowedsignificantlysuppressedadditioninvestigatedmolecularmechanismcontributesCblproto-oncogeneE3ubiquitinproteinligasetargetgeneectopiccanattenuateinhibitoryeffectcellCONCLUSIONS:newregulatoryaxisregulateBreastInvasionProliferation

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