MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion

Details

• Alternative Title:
  Oncotarget
• Personal Author:
  Imani, Saber ; Wei, Chunli ; Cheng, Jingliang ; Asaduzzaman Khan, Md. ; Fu, Shangyi ; Yang, Luquan ; Tania, Mousumi ; Zhang, Xianqin ; Xiao, Xiuli ; Zhang, Xianning ; Fu, Junjiang
• Description:
  MicroRNA-34a (miR-34a) plays an essential role against tumorigenesis and progression of cancer metastasis. Here, we analyzed the expression, targets and functional effects of miR-34a on epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs), such as TWIST1, SLUG and ZEB1/2, and an EMT-inducing protein NOTCH1 in breast cancer (BC) cell migration and invasion and its correlation with tumorigenesis and clinical outcomes. Expression of miR-34a is downregulated in human metastatic breast cancers (MBC) compared to normal breast tissues and is negatively correlated with clinicopathological features of MBC patients. Ectopic expression of miR-34a in MBC cell-line BT-549 significantly inhibits cell migration and invasion, but exhibits no clear effect on BC cell growth. We found that miR-34a is able to inactivate EMT signaling pathway with mediatory of NOTCH1, TWIST1, and ZEB1 upon 3'-UTR activity in MBC cell lines, but has no inhibitory effects on SLUG and ZEB2. Furthermore, we investigated the synergistic effects of Thymoquinone (TQ) and miR-34a together on the expression of EMT-associated proteins. Results showed that co-delivery of miR-34a and TQ is able to inactivate EMT signaling pathway by directly targeting TWIST1 and ZEB1 in BT-549 cell line, indicating that they might be a promising therapeutic combination against breast cancer metastasis. Epigenetic inactivation of the EMT-TFs/miR-34a pathway can potentially alter the equilibrium of these regulations, facilitating EMT and metastasis in BC. Altogether, our findings suggest that miR-34a alone could serve as a potential therapeutic agent for MBC, and together with TQ, their therapeutic potential is synergistically enhanced.
• Subjects:
  Breast Cancer Epithelial-mesenchymal Transition Metastasis MicroRNA-34a Research Paper Thymoquinone
• Source:
  Oncotarget. 2017; 8(13):21362-21379.
• Pubmed ID:
  28423483
• Pubmed Central ID:
  PMC5400590
• Document Type:
  Journal Article
• Funding:
  U38 SH000001/SH/NCHS CDC HHS/United States
• Volume:
  8
• Issue:
  13
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:48aa60abd7e43202a897361ae26c4a30da53c7d6a64ef65ead59ae24768ba1c9
• Download URL:
  https://stacks.cdc.gov/view/cdc/46572/cdc_46572_DS1.pdf
• File Type:
  [PDF - 6.75 MB ]