Exosomal MicroRNA-221-3p Confers Adriamycin Resistance in Breast Cancer Cells by Targeting PIK3R1
Authors: Rong Wang
Mingmei Yao
Yandong Cheng
Jinguo Lai
Lu Cheng
Xiaoping Pan
Xiaolv Hong
Na Hu
Journal: Frontiers in Oncology (2020)
Discipline: CLINICAL MEDICINE
Keywords: adriamycin; breast cancer; drug resistance; exosomes; microRNA-221-3p
Affiliations: Clinical Laboratory, Huadu Hospital, Southern Medical University, Guangzhou, China., Department of Infectious Diseases, Huadu Hospital, Southern Medical University, Guangzhou, China., Department of Breast Surgery, Huadu Hospital, Southern Medical University, Guangzhou, China.

Abstract:  Drug resistance in breast cancer (BC) cells continues to be a stern obstacle hindering BC treatment. Adriamycin (ADR) is a frequently employed chemotherapy agent used to treat BC. The exosomal transfer of microRNAs (miRNAs) has been reported to enhance the drug-resistance of BC cells. Herein, we first sought to elucidate the possible role of the exosomal transfer of miR-221-3p in the drug resistance of MCF-7 cells to ADR. Differentially expressed genes (DEGs) were initially screened through microarray analysis in BC drug resistance-related datasets. Next, the expression of miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was quantified in ADR-resistant MCF-7 (MCF-7/ADR) and ADR-sensitive MCF-7 (MCF-7/S) cell lines, after which exosomes were separated and identified in each cell line. Target relationship between miR-221-3p and PIK3R1 was validated by a dual-luciferase reporter assay. Next, the expression of miR-221-3p and PIK3R1 was altered to clarify their effects on the resistance of MCF-7 cells to ADR in vitro and in vivo. PIK3R1 was identified as a BC drug resistance-related DEG, with the regulatory miR-221-3p subsequently obtained. Moreover, the MCF-7/ADR cells exhibited a low expression of PIK3R1 and a high expression of miR-221-3p. Notably, PIK3R1 was identified as a target gene of miR-221-3p. The overexpression of miR-221-3p in MCF-7/ADR cell-derived exosomes promoted ADR resistance in MCF-7/S cells via the PI3K/AKT signaling pathway. The in vitro results were reproducible in in vivo assays. Taken together, drug-resistant BC cell-derived exosomal miR-221-3p can promote the resistance of BC cells to ADR by targeting PIK3R1 via the PI3K/AKT signaling pathway in vitro and in vivo. These findings provide encouraging insights and provide perspectives for further investigation into the BC drug resistance mechanism. 

Retracted: Yes

PubPeer comments:
 Retracted [30 December 2021] . ------------------------- The journal and Chief Editors retract the 30 April 2020 article cited above. Following publication, concerns were raised regarding the validity of the data in the article. The authors failed to provide the raw data or a satisfactory explanation during the investigation, which was conducted in accordance with Frontiersu2019 policies. Given the concerns, and the lack of raw data, the editors no longer have confidence in the findings presented in the article. u200b This retraction was approved by the Chief Editors of Frontiers in Oncology and the Chief Executive Editor of Frontiers. The authors have not responded to any correspondence regarding the retraction. --------------------------------------- The Western Blots all hew to a  row of bowties style:   Many recent [products of the Contractor papermill] display the same stylised appearance. Here is a montage that I prepared earlier. Clockwise from upper left: - [Wang et al (2020)] - [Gao et al (2021)] - [Chen et al (2020)] - [He et al (2021)] .  In addition, WBs from [Lv et al (2020)] *[retracted]*  Also the WBs from [Gao, Feng Tan (2019)] *[retracted]*.  , 
 The paper ends this way:  **ACKNOWLEDGMENTS** We would like to express our sincere appreciation to the reviewers for critical comments on this article. This kind of conventionalised acknowledgement is another hallmark of the papermill. ,