LINC00355 regulates p27KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer

Abdallah M Eteleeb; Prasanth K Thunuguntla; Kyla Z Gelev; Cynthia Y Tang; Emily B Rozycki; Alexander Miller; Jonathan T Lei; Reyka G Jayasinghe; Ha X Dang; Nicole M White; Jorge S Reis-Filho; Elaine R Mardis; Matthew J Ellis; Li Ding; Jessica M Silva-Fisher; Christopher A Maher

doi:10.1038/s41523-022-00412-2

LINC00355 regulates p27^KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer

NPJ Breast Cancer. 2022 Apr 13;8(1):49. doi: 10.1038/s41523-022-00412-2.

Authors

Abdallah M Eteleeb¹, Prasanth K Thunuguntla¹, Kyla Z Gelev¹, Cynthia Y Tang², Emily B Rozycki¹, Alexander Miller¹, Jonathan T Lei³, Reyka G Jayasinghe^{1

4}, Ha X Dang^{1

4

5}, Nicole M White^{1

5}, Jorge S Reis-Filho⁶, Elaine R Mardis⁷, Matthew J Ellis³, Li Ding^{1

4

5}, Jessica M Silva-Fisher^#^{8

9}, Christopher A Maher^#^{10

11

12

13}

Affiliations

¹ Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
² University of Missouri, Columbia, MO, 65211, USA.
³ Baylor College of Medicine, Houston, TX, 77030, USA.
⁴ The McDonnell Genome Institute, St. Louis, MO, USA.
⁵ Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
⁶ Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁷ Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
⁸ Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA. silvajm@wustl.edu.
⁹ Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. silvajm@wustl.edu.
¹⁰ Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA. christophermaher@wustl.edu.
¹¹ The McDonnell Genome Institute, St. Louis, MO, USA. christophermaher@wustl.edu.
¹² Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. christophermaher@wustl.edu.
¹³ Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, USA. christophermaher@wustl.edu.

^# Contributed equally.

Abstract

Late-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA, LINC00355, in BC and MCF7 long-term estrogen deprived cell lines decreases cellular invasion and proliferation. Subsequent mechanistic studies show that LINC00355 binds to MENIN and changes occupancy at the CDKN1B promoter to decrease p27^Kip. In summary, this is a key study discovering lncRNAs in LSR BC and LINC00355 association with epigenetic regulation and proliferation in BC.

Abstract

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