, Volume 24, Issue 1–2, pp 108–118 | Cite as

MicroRNA-663 antagonizes apoptosis antagonizing transcription factor to induce apoptosis in epithelial cells

  • M. R. BenakanakereEmail author
  • J. Zhao
  • L. Finoti
  • R. Schattner
  • M. Odabas-Yigit
  • D. F. Kinane


MicroRNAs are small functional RNAs that modulate various biological processes in cells by interfering with gene translation. We have previously demonstrated that certain miRNAs play a crucial role in the innate immune responses of human oral epithelial cells to Porphyromonas gingivalis. While addressing the mechanisms of P. gingivalis induced apoptosis in these cells, we discovered that certain miRNAs are upregulated upon stimulation with live bacteria. These upregulated miRNAs include hsa-miR-584, hsa-miR-572, hsa-miR-210, hsa-miR-492, hsa-miR-623 and hsa-miR-663. Further analysis revealed an unexpected role for hsa-miR-663 (miR-663). To further evaluate miR-663 function, we overexpressed miR-663 in epithelial cells which resulted in cellular apoptosis. The bioinformatics analysis of the miR-663 target prediction, revealed a strong binding affinity to a 3′ UTR region of Apoptosis Antagonizing Transcription Factor (AATF) mRNA. To demonstrate the binding of miR-663 to AATF mRNA, the putative miR-663 target site within the 3′-UTR region of AATF was cloned in luciferase vector and transfected to HEK293T cells. Luminescence data showed the downregulation of luciferase activity in cells that had the full length target region of the putative binding site, confirming that AATF is one of the targets for miR-663. This prompted us to further evaluate its role in a cancer cell line (MCF-7) to determine miR-663s’ apoptotic function. The overexpression of miR-663 led to a significant increase in apoptosis of MCF-7 cells. Taken together, miR-663 may function as an ‘apoptomiR’ by inhibiting the anti-apoptotic gene AATF to induce apoptosis. These findings could have therapeutic implications for epithelial cell targeting in cancer therapy.


Porphyromonas gingivalis MicroRNAs Primary oral epithelial cells Cell death ApoptomiRs 



This work was supported in part by National Institutes of Health Grant (R01DE024160). BMR is a recipient of Rabinowitz award for research excellence and thanks the Rabinowitz family for their generous support.

Supplementary material

10495_2018_1513_MOESM1_ESM.docx (128 kb)
Supplementary material 1 (DOCX 128 KB)


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Authors and Affiliations

  • M. R. Benakanakere
    • 1
    Email author
  • J. Zhao
    • 2
    • 3
  • L. Finoti
    • 1
  • R. Schattner
    • 1
  • M. Odabas-Yigit
    • 1
  • D. F. Kinane
    • 4
  1. 1.Department of Periodontics, School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Pathology, School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of PathologyWayne State University School of MedicineDetroitUSA
  4. 4.Division of Periodontology, School of Dental MedicineUniversity of Geneva Faculty of MedicineGenevaSwitzerland

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