Research Paper Volume 12, Issue 20 pp 20658—20683
Cross-talk between the ER pathway and the lncRNA MAFG-AS1/miR-339-5p/ CDK2 axis promotes progression of ER+ breast cancer and confers tamoxifen resistance
- 1 Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China
- 2 Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang 110001, China
- 3 Liaoning Province Clinical Research Center for Cancer, Shenyang 110001, China
- 4 Department of Breast Surgery, The First Hospital of China Medical University, Shenyang 110001, China
Received: March 17, 2020 Accepted: July 7, 2020 Published: October 24, 2020
https://doi.org/10.18632/aging.103966How to Cite
Copyright: © 2020 Feng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Hormone receptor-positive breast cancer accounts for around 75% of breast cancers. The estrogen receptor pathway promotes tumor progression and endocrine resistance. Recently, the cross-talk between the ER signaling pathway and cell cycle regulation has been identified. It is necessary to determine the underlying molecular mechanisms involved in the ER signaling pathway and find new target genes for prognosis and drug resistance in ER+ breast cancer. In this study, lncRNA MAFG-AS1 was shown to be up-regulated and associated with poor prognosis in ER+ breast cancer. Functionally, down-regulation of MAFG-AS1 could inhibit cell proliferation and promote apoptosis. In addition, MAFG-AS1 which contained an estrogen-responsive element could promote CDK2 expression by sponging miR-339-5p. Subsequently, MAFG-AS1 and CDK2 were found to be up-regulated in tamoxifen-resistant MCF-7 cells. Cross-talk between the ER signaling pathway and cell cycle conducted by MAFG-AS1 and CDK2 could promote tamoxifen resistance. In conclusion, our study indicated that estrogen-responsive lncRNA MAFG-AS1 up-regulated CDK2 by sponging miR-339-5p, which promoted ER+ breast cancer proliferation. Cross-talk between the ER signaling pathway and cell cycle suggested that lncRNA MAFG-AS1 is a potential biomarker and therapeutic target in ER+ breast cancer. CDK2 inhibitors may be applied to endocrine resistance therapy.
Abbreviations
ASO: antisense oligonucleotides; ceRNA: Competing endogenous RNA; CDK2: cyclin-dependent kinases 2; ChIP: Chromatin immunoprecipitation; ER: estrogen receptor; FOXO1: forkhead transcription factor 1; GEO: Gene expression omnibus; IHC: Immunohistochemistry; ISH: In situ hybridization; lncRNA: Long non-coding RNA; MAFG-AS1: MAFG antisense RNA 1; qPCR: Quantitative real-time PCR; RIP: RNA immunoprecipitation; TCGA: the cancer genome atlas.