Integrative analysis of transcriptional profile reveals LINC00052 as a suppressor of breast cancer cell migration

Article type: Research Article

Authors: Sanchez-Lopez, Jose Manuel^{a; b} | Mandujano-Tinoco, Edna Ayerim^{a; c} | Garcia-Venzor, Alfredo^a | Lozada-Rodriguez, Laura Fatima^a | Zampedri, Cecilia^a | Uribe-Carvajal, Salvador^d | Melendez-Zajgla, Jorge^e | Maldonado, Vilma^a | Lizarraga, Floria^{a; *}

Affiliations: [a] Epigenetics Laboratory, Instituto Nacional de Medicina Genómica, Mexico City, Mexico | [b] Postgraduate Program in Biological Sciences, Faculty of Medicine, Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico City, Mexico | [c] Laboratory of Connective Tissue, Centro Nacional de Investigación y Atención de Quemados, Instituto Nacional de Rehabilitación Luís Guillermo Ibarra Ibarra, Mexico City, Mexico | [d] Department of Molecular Genetics, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico | [e] Functional Genomics Laboratory, Instituto Nacional de Medicina Genómica, Mexico City, Mexico

Correspondence: [*] Corresponding author: Floria Lizarraga, Periferico Sur 4809. Col. El Arenal Tepepan. Delegacion Tlalpan. CP.14610. Mexico City, Mexico. Tel.: +52 55 5350 1188; E-mail: fjlizarraga@%****␣cbm-30-cbm200337_temp.tex␣Line␣25␣****inmegen.gob.mx.

Abstract: BACKGROUND: Long-non-coding RNAs, a class of transcripts with lengths > 200 nt, play key roles in tumour progression. Previous reports revealed that LINC00052 (long intergenic non-coding RNA 00052) was strongly downregulated during breast cancer multicellular spheroids formation and suggested a role in cell migration and oxidative metabolism. OBJECTIVE: To examine the function of LINC00052 in MCF-7 breast cancer cells. METHODS: Loss-of-function studies were performed to evaluate LINC00052 role on MCF-7 breast cancer cells. Microarray expression assays were performed to determine genes and cellular functions modified after LINC00052 knockdown. Next, the impact of LINC00052 depletion on MCF-7 cell respiration and migration was evaluated. RESULTS: 1,081 genes were differentially expressed upon LINC00052 inhibition. Gene set enrichment analysis, Gene Ontology and Key Pathway Advisor analysis showed that signalling networks related to cell migration and oxidative phosphorylation were enriched. However, whereas LINC00052 knockdown in MCF-7 cells revealed marginal difference in oxygen consumption rates when compared with control cells, LINC00052 inhibition enhanced cell migration in vitro and in vivo, as observed using a Zebrafish embryo xenotransplant model. CONCLUSION: Our data show that LINC00052 modulates MCF-7 cell migration. Genome-wide microarray experiments suggest that cancer cell migration is affected by LINC00052 through cytoskeleton modulation and Notch/β-catenin/NF-κB signalling pathways.

Keywords: LINC00052, cell migration, transcriptome analysis, breast cancer

DOI: 10.3233/CBM-200337

Journal: Cancer Biomarkers, vol. 30, no. 4, pp. 365-379, 2021