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microRNA-205 represses breast cancer metastasis by perturbing the rab coupling protein [RCP]-mediated integrin β1 recycling on the membrane

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Abstract

During cancer cell invasion, integrin undergoes constant endo/exocytic trafficking. It has been found that the recycling ability of integrin β1 through Rab11-controlled long loop pathways is directly associated with cancer invasion. Previous studies showed that gain-of-function mutant p53 regulates the Rab-coupling protein [RCP]-mediated integrin β1 recycling by inactivating tumor suppressor TAp63. So, we were interested to investigate the involvement of miR-205 in this process. In the current study first, we evaluated that the lower expression of miR-205 in MDA-MB-231 cell line is associated with high motility and invasiveness. Further investigation corroborated that miR-205 directly targets RCP resulting in attenuated RCP-mediated integrin β1 recycling. Overexpression of TAp63 validates our in vitro findings. To appraise the anti-metastatic role of miR-205, we developed two in vivo experimental models- xenograft-chick embryo and xenograft-immunosuppressed BALB/c mice. Our in vivo results support the negative effect of miR-205 on metastasis. Therefore, these findings advocate the tumor suppressor activity of miR-205 in breast cancer cells and suggest that in the future development of miR-205-targeting RNAi therapeutics could be a smart alternative approach to prevent the metastatic fate of the disease.

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Data Availability

Privacy/ethical restrictions: The raw data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

We would like to acknowledge Department of Biotechnology [Sanction no. 6242-P23/RGCB/PMD/DBT/ARAD-2015 dated 29th July 2015], Council of Scientific and Industrial Research, India [CSIR Sanction no. 09/028[0966]/2016-EMR-I]; DST-NANOMISSION, India [SR/NM/NS-1185/2015[g] ; DBT-Ayush India, [sanction no: Z.28015/29/2016-HPC [EMR]-AYUSH-A], DST INSPIRE Faculty Scheme [sanction no: IFA12-LSBM-40], Govt. of India and DST-INSPIRE, Department of Science and Technology, for funding support. Authors would like to thank Mr. Abir Chakraborty and Dr. Sneha Mitra for their technical support.

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Author notes

  1. Saurav Bhattacharya

    Present address: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA

  2. Manisha Ahir

    Present address: Baylor College of Medicine, Houston, TX, USA

  3. Saurav Bhattacharya and Sushmita Sarker contributed equally to this work.

Authors and Affiliations

  1. Centre for Research in Nanoscience and Nanotechnology, Technology Campus, University of Calcutta, JD-2, Sector-III, Salt Lake, Kolkata, 700106, West Bengal, India

    Saurav Bhattacharya, Sushmita Sarker, Shaswati Das & Manisha Ahir

  2. Department of Physiology, University of Calcutta, 92 Acharya Prafulla Chandra Road, Kolkata, 700009, West Bengal, India

    Sreya Chattopadhyay

  3. Amity Institute of Biotechnology, Amity University, Kolkata. Major Arterial Road [South-East], Action Area II, Newtown, Kolkata, 700135, West Bengal, India

    Swatilekha Ghosh

  4. Department of Life science & Bio-technology, Jadavpur University, Kolkata, West Bengal, India

    Arghya Adhikary

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Saurav Bhattacharya: Conceptualization, methodology, data leading curation, investigation, writing - original draft. Sushmita Sarker: Methodology, formal Analysis, data curation. Shaswati Das: Formal analysis, data curation. Manisha Ahir: Formal analysis, data curation.: Sreya Chattopadhyay: Formal analysis. Swatilekha Ghosh: Formal analysis, writing review & editing. Arghya Adhikary: Conceptualization, supervision, project administration, funding acquisition, writing - review & editing.

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Bhattacharya, S., Sarker, S., Das, S. et al. microRNA-205 represses breast cancer metastasis by perturbing the rab coupling protein [RCP]-mediated integrin β1 recycling on the membrane. Apoptosis 29, 191–209 (2024). https://doi.org/10.1007/s10495-023-01912-7

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