123P - Stabilization of SDCBP oncoprotein and aiding breast cancer growth and metastasis: The role of A2BP1

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Breast Cancer, Metastatic
Translational Research
Presenter Annesha Chatterjee
Citation Annals of Oncology (2016) 27 (suppl_9): ix35-ix41. 10.1093/annonc/mdw577
Authors A. Chatterjee, S. Jana, A. Bhattacharyya
  • Department Of Zoology, University of Calcutta, 700019 - Kolkata/IN

Abstract

Background

The main cause of breast cancer related death is metastasis and resistance to chemotherapy. Syndecan binding protein was reported to be responsible for cell migration, invasion and pseudopodia formation, all of which are links to tumor metastasis in different type of cancers including breast cancer .Our study aims to describe the stability of SDCBP mRNA during breast cancer.

Methods

Gene expression status within the breast cancer (BC) samples and cell lines was analyzed by real time PCR and immunoblotting and also miR-103a expression was analyzed by real time PCR. Bioinformatic analysis of the SDCBP 3’ UTR for probable binding of RNA binding protein was done by RBPDB. Docking study and RNA EMSA was performed. Functional characterization of A2BP1 in BC growth and metastasis was performed by over and under expression of A2BP1 along with simultaneous inhibition of miR-103a.

Results

SDCBP was found to be overexpressed in highly metastatic BC tissue. miR-103a was found to be significantly overexpressed in highly metastatic cell lines and metastatic tissue samples, a targeting miRNA of SDCBP. So, to address this paradox of both miR-103a and its target gene SDCBP overexpression, a bioinformatic analysis revel that A2BP1 (RNA binding protein) might be interacting with 3’UTR SDCBP. RNA EMSA study confirmed the binding of A2BP1 within the 3’UTR of SDCBP. Next, overexpression and underexpression of A2BP1 was done to analyse its effect on BC progression and metastasis by modulating the expression of SDCBP. Finally, A2BP1 underexpression along with miR-103a inhibition study was done to confirm that A2BP1 stabilizes SDCBP and hence miR-103a cannot bind to its 3’ UTR and degrade it.

Conclusions

In summary, our study defines the stabilization of the oncoprotein SDCBP mRNA by the RNA binding protein A2BP1, competing with miR-103a seeding region of the 3’UTR region of SDCBP.

Clinical trial indentification

Legal entity responsible for the study

University of Calcutta, Kolkata and Department of Biotechnology, Government of India

Funding

Department of Biotechnology, Government of India

Disclosure

All authors have declared no conflicts of interest.