Issue 16, 2022

MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer

Abstract

RNA interference is a promising way to treat cancer and the construction of a stable drug delivery system is critically important for its application. Gelatin nanospheres (GNs) comprise a biodegradable drug vehicle with excellent biocompatibility, but there are limited studies on its delivery and role in the stabilization of miRNA and siRNA. Breast cancer is the most diagnosed type of female cancer worldwide. Abnormal miRNA expression is closely related to the occurrence and progression of estrogen receptor-positive (ER+) breast cancer. In this study, miR-4458 was upregulated in ER+ breast cancer and could inhibit MCF-7 cell viability, colony formation, migration, and invasion. Collagen type XI alpha 1 (COL11A1) was identified as a directly interacting protein of miR-4458 and an important component of the extracellular matrix. High COL11A1 expression was positively correlated with poor prognosis, lower overall survival, disease-free survival, and a late tumor-node-metastasis stage. COL11A1 knockdown could inhibit MCF-7 cell migration and invasion. GNs were used to load a miR-4458 mimic or COL11A1 siRNA (si-COL11A1) to achieve sustained and controlled release in xenograft nude mice. Their tumor volume was decreased, tumor cell apoptosis was promoted, and hepatic metastasis was significantly inhibited. Moreover, the DDR2/SRC signaling pathway was inactivated after transfection with the miR-4458 mimic and si-COL11A1. In conclusion, GNs can be potentially used to deliver siRNA or miRNA, and miR-4458 and COL11A1 can be possible targets for ER+ breast cancer treatment.

Graphical abstract: MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer

Supplementary files

Article information

Article type
Paper
Submitted
08 Apr 2022
Accepted
20 Jun 2022
First published
22 Jun 2022

Biomater. Sci., 2022,10, 4596-4611

MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer

J. Liu, C. Yang, Q. Chen, T. Yu, S. Zhang, W. Guo, L. Luo, G. Zhao, D. Yin and C. Zhang, Biomater. Sci., 2022, 10, 4596 DOI: 10.1039/D2BM00543C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements