eISSN: 1897-4309
ISSN: 1428-2526
Contemporary Oncology/Współczesna Onkologia
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4/2022
vol. 26
 
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abstract:
Original paper

The tamoxifen-regulated, long non-coding RNA LINC00992 affects proliferation, migration, and expression of tamoxifen resistanceassociated genes in MCF-7 breast cancer cells

Sebastian Graf
1, 2
,
Johannes Haybaeck
3, 4
,
Gerhard Behre
5
,
Thomas Kalinski
1
,
Norbert Nass
1, 5

  1. Department of Pathology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
  2. Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
  3. Diagnostic and Research Center for Molecular BioMedicine, Institute of Pathology, Medical University Graz, Austria
  4. Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria
  5. Dessau Medical Center and Brandenburg Medical School Theodor Fontane (MHB), Department for Internal Medicine I, Dessau, Germany
Contemp Oncol (Pozn) 2022; 26 (4): 294–305
Online publish date: 2023/01/30
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Introduction:
Tamoxifen-adapted MCF-7 breast cancer cells (MCF-7-TAM-R) are a model for acquired tamoxifen resistance in oestrogen receptor-positive breast cancer. In this system, the expression of long-non-coding RNA LINC00992 is decreased. LINC00992 might therefore contribute to tamoxifen adaption and associated gene expres­sion changes. Here, we investigated whether a modulation of LINC00992 modifies gene expression, proliferation, and migration.

Material and methods:
Up- and down-­ regulation of LINC00992 was performed using plasmid vectors and siRNA. Gene expression was measured via nCounter® and quantitative real-time polymerase chain reaction. Database analysis was performed using GEPIA2 and cBioportal. Furthermore, we performed scratch assays, colony-forming assays, and proliferation assays with MCF-7 and MCF-7-TAM-R after up-regulation of LINC00992.

Results:
Up- and down-regulation of LINC00992 caused gene expression changes in 4 of the 42 tamoxifen-regulated genes tested. Especially ubiquitin D, single-minded homologue 1 (SIM1) carcinoembryonic antigen-related cell adhesion molecule 5 and the G-protein coupled oestrogen receptor 1 were affected. In tamoxifen-adapted MCF-7-TAM-R cells, LINC00992 overexpression resulted in augmented viability and proliferation and enhanced migration. Database analyses revealed that luminal breast cancers have increased expression of LINC00992 compared to Her2-type/neu- or basal type. Furthermore, higher expression of LINC00992 was associated with poor prognosis in luminal-A carcinomas.

Conclusions:
Changes in the expression of tamoxifen-regulated genes could be induced by manipulating LINC00992’s abundance, suggesting that it is at least partially involved in the establishment of the tamoxifen-induced gene expression pattern. LINC00992 may also serve as a prognostic biomarker and may indicate the development of tamoxifen resistance. 

keywords:

breast cancer, tamoxifen resistance, long non-coding RNA, LINC00992, gene expression analysis, MCF-7

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