Epigenetic upregulation of mage-a isoforms promotes breast cancer cell aggressiveness

Chaeun Oh, Hwa Ryeon Kim, Sumin Oh, Je Yeong Ko, Yesol Kim, Keunsoo Kang, Young Yang, Jongmin Kim, Jong Hoon Park, Jae Seok Roe, Kyung Hyun Yoo

Research output: Contribution to journalArticlepeer-review

Abstract

After decades-long efforts to diagnose and treat breast cancer, the management strategy that has proved most successful to date is molecular-subtype-specific inhibition of the hormone receptors and HER2 that are expressed by individual cancers. Melanoma-associated antigen (MAGE) proteins comprise >40 highly conserved members that contain the MAGE homology domain. They are often overexpressed in multiple cancers and contribute to cancer progression and metastasis. However, it remains unclear whether the biological activity arising from MAGE gene expression is associated with breast cancer subtypes. In this study, we analyzed the RNA-sequencing (RNA-seq) data of 70 breast cancer cell lines and found that MAGEA12 and MAGEA3 were highly expressed in a subset of these lines. Significantly, MAGEA12 and MAGEA3 expression levels were independent of hormone receptor expression levels but were closely associated with markers of active histone modifications. This indicates that overexpression of these genes is attributable to epigenetic deregulation. RNA-seq of MAGEA12-depleted cells was then used to identify 382 candidate targets of MAGEA12 that were downregulated by MAGEA12 depletion. Furthermore, our gain-of-function experiments showed that MAGEA12 overexpression promoted aggressive behaviors of malignant breast cancer cells, including enhancing their cell migration and invasion. These changes were associated with increased epigenetic deregulation of the MAGEA12 signature genes. Thus, MAGEA12 may play an important role in breast cancer malignancy. Taken together, our findings suggest that MAGEA12 could be a promising therapeutic target in breast cancer, and its overexpression and epigenetic changes could serve as subtype classification biomarkers.

Original languageEnglish
Article number3176
JournalCancers
Volume13
Issue number13
DOIs
Publication statusPublished - 2021 Jul 1

Bibliographical note

Funding Information:
Funding: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MIST) (2020R1A2C2012658) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1A6A1A03038890) to K.H.Y. This research was also funded by a NRF grant funded by MSIT (2021R1A2C4001420) to J.R., and by the Brain Korea 21 FOUR program to J.R. and H.K. H.K. was also supported by the Program for Returners into R&D for Women in Science, Engineering, and Technology (WISET).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Epigenetic upregulation of mage-a isoforms promotes breast cancer cell aggressiveness'. Together they form a unique fingerprint.

Cite this