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Poster display session

2512 - Dual targeting of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) by miR-4317 displays a synergistic efficacy in repressing Breast Cancer progression

Date

11 Sep 2017

Session

Poster display session

Topics

Translational Research;  Breast Cancer

Presenters

Rana Youness

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

R.A. Youness1, R.A. Assal2, E. Khallaf3, H.M. Hafez3, A.A. Abdelmotaal1, M.Z. Gad4

Author affiliations

  • 1 Pharmaceutical Biology Department, Faculty Of Pharmacy And Biotechnology, German University in Cairo, 11835 - Cairo/EG
  • 2 Pharmacology And Toxicology Department, Faculty Of Pharmacy And Biotechnology, German University in Cairo, 11835 - Cairo/EG
  • 3 General Surgery Department, Faculty Of Medicine, Cairo University, 12613 - Cairo/EG
  • 4 Biochemistry Department, Faculty Of Pharmacy And Biotechnology, German University in Cairo, 11835 - Cairo/EG
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Resources

Abstract 2512

Background

Recently, hydrogen sulphide (H2S) and its synthesizing enzymes, CBS and CSE, have been casted as pleiotropic regulators in the malignant transformation process. H2S paradoxically acts as oncogenic mediator in ovarian and liver cancers, and as tumor suppressor in prostate and gastric carcinomas. However, the link between H2S and Breast cancer (BC) remains unclear. Thus we aimed at unraveling the association between H2S and its synthesizing enzymes in BC progression. Furthermore, it was essential to evaluate their possible adoption as therapeutic targets in BC through their dual targeting by short non-coding RNAs.

Methods

Breast tissues were collected from 30 BC patients. Ki67 levels were quantified using immunohistochemistry. MDA-MB-231 and MCF7 cells were cultured and transfected with different oligonucleotides and/or treated with NaHS, an exogenous source of H2S. Total RNA was extracted and quantified by qRT-PCR. Cellular viability, proliferation, and migation were measured using MTT, BrdU and scratch assays respectively. Bioinformatic analysis was performed to predict novel miRNAs that could target both CBS and CSE.

Results

CBS and CSE were significantly upregulated in BC tissues. Patients with high Ki67 scores showed the highest expression levels of CBS and CSE. Knocking down of CBS and CSE using siRNAs resulted in a significant attenuation of different hallmarks of BC. On the other hand, NaHS resulted in an increase in BC progression. miR-4317 was found to putatively target both CBS and CSE oncogenes with high binding scores. Ectopic expression of miR-4317 in BC cell lines resulted in a simultaneous reduction of CBS and CSE transcripts which was associated with a concomitant reduction in cellular viability, proliferation and migration. Finally, co-treatment of miR-4317 and NaHS resulted in abrogation of miR-4317 tumor suppressor activity.

Conclusions

This study showed a marked upregulation of CBS and CSE in BC tissues and characterized them as aggressive oncogenic drivers in BC. Moreover, miR-4317, a novel tumor suppressor in BC, displayed a synergistic effect in halting BC progression via twin-targeting CBS and CSE and diminishing H2S levels in BC cell lines.

Clinical trial identification

Legal entity responsible for the study

German University in Cairo

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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