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Molecular Biology Reports

, Volume 46, Issue 6, pp 6617–6624 | Cite as

Dysregulation of non-histone molecule miR205 and LRG1 post-transcriptional de-regulation by SETD1A in triple negative breast cancer

  • Ezanee Azlina Mohamad HanifEmail author
Short Communication
  • 52 Downloads

Abstract

FEC chemo-resistance in triple negative breast cancer (TNBC) remains a challenge. Therefore it is crucial to determine the right treatment regime by understanding molecular mechanisms of driver regulators involved in the progression of TNBCs. This study aims to understand SETD1A mechanisms in TNBC development in two TNBC cell lines. SETD1A was transiently transfected in MDA-MB-468 (FEC good prognosis) and Hs578T (FEC poor prognosis). Regulation of potential targets miR205, EMT marker ZEB1 and LRG1 and proliferative marker Ki-67 were tested by RqPCR to elucidate SETD1A interactions. This study displayed significant recovery of miR205 with SETD1A depletion and reduction of ZEB1 in MDA-MB-468. However, ZEB1 remained unchanged in Hs578T indicating ZEB1 regulation may be outcompeted by other mechanisms associated with aggressive cell line characteristics and the expression of endogenous ZEB1 was relatively high in Hs578T. Elevation of LRG1 and declined Ki-67 were observed by SETD1A knocked down. Enhanced expression was observed by LRG1 in Hs578T and not in MDA-MB-468 suggesting LRG1 contributed to distinct poor FEC outcome in TNBCs. The underlying mechanism of SETD1A in miR205/ZEB1/Ki-67/LRG1 axis needs further evaluation. Whether abrogation of the pathway is indeed associated with transcriptional or post-transcriptional activation in TNBC cell lines models, clearly validation in clinical samples is warranted to achieve its prognostic and therapeutic values in TNBCs.

Keywords

Triple negative breast cancers TNBCs SETD1A miR205 EMT 

Notes

Acknowledgements

This study was funded by Geran Galakan Penyelidik Muda (Young Investigator Grant) (Project Code: GGPM-2017-103).

Funding

This study was funded by Geran Galakan Penyelidik Muda (Young Investigator Grant) (Project Code: GGPM-2017-103).

Compliance with ethical standards

Conflict of interest

There was no conflict of interest throughout the study.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.UKM Medical Molecular Biology Institute (UMBI)University Kebangsaan Malaysia Medical CentreKuala LumpurMalaysia

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