title: microRNA-761 induces aggressive phenotypes in triple-negative breast cancer cells by repressing TRIM29 expression.
abstract: OBJECTIVE
  Despite advances that have been made in systemic chemotherapy, the prognosis of advanced triple-negative breast cancer (TNBC) patients is still poor. The identification of key factors governing TNBC development is considered imperative for the development of novel effective therapeutic approaches. Previously, it has been reported that microRNA (miR)-761 may act as either a tumor suppressor or as an oncogene in different types of cancer. Here, we aimed at assessing the biological role of this miRNA in TNBC.
  
  
  METHODS
  First, we measured the expression of miR-761 in primary breast cancer tissues and breast cancer-derived cell lines using qRT-PCR. Subsequently, over-expression and silencing experiments were performed to determine the role of miR-761 in TNBC cell proliferation, colony formation, migration and invasion in vitro. The in vivo role of miR-761 in TNBC growth and metastasis was determined in mouse models. Bioinformatics analyses, dual-luciferase reporter assays, Western blot analyses and rescue experiments were performed to identify miR-761 target gene(s).
  
  
  RESULTS
  We found that miR-761 was up-regulated in primary breast cancer tissues and its derived cell lines and, particularly, in TNBC tissues and cell lines. We also found that exogenous miR-761 over-expression augmented in vitro TNBC cell proliferation, colony formation, migration and invasion, whereas miR-761 down-regulation impaired these features. In vivo, we found that miR-761 over-expression facilitated TNBC growth and lung metastasis. Mechanistically, miR-761 was found to negatively regulate the expression of tripartite motif-containing 29 (TRIM29) in TNBC cells by binding to the 3'-untranslated region of its mRNA. In conformity with these results, a significant negative correlation between miR-761 expression and TRIM29 protein expression was noted in primary TNBC tissues (r = -0.452, p = 0.0126). We also found that exogenous TRIM29 over-expression reversed the proliferative and invasive capacities of TNBC cells.
  
  
  CONCLUSIONS
  Our data indicate that miR-761 acts as an oncogene in TNBC. This mode of action can, at least partially, be ascribed to the down-regulation of its target TRIM29. We suggest that miR-761 may serve as a promising therapeutic target for TNBC.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Guang-Cheng
authors.initials: GC
authors.lastname: Guo
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. ggc503@126.com.
authors.forename: Jia-Xiang
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Han
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Lian-Ping
authors.initials: LP
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D035683:MicroRNAs; C087296:TRIM29 protein, human; D014157:Transcription Factors; C000610045:microRNA761 microRNA, human
keywords: Metastasis; TRIM29; Therapeutic target; Triple-negative breast cancer; miR-761