Re-expression of miR-200s in claudin‐low mammary tumor cells alters cell shape and reduces proliferation and invasion potentially through modulating other miRNAs and SUZ12 regulated genes
Autor: | G. Conquer-van Heumen, K. L. Watson, K. Simpson, C. J. Martin, M. Roth, Roger A. Moorehead |
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Rok vydání: | 2021 |
Předmět: |
Cancer Research
H3K27me3 Biology Cell morphology lcsh:RC254-282 03 medical and health sciences Histone H3 0302 clinical medicine microRNA Gene expression SUZ12 miRNA sequencing Genetics lcsh:QH573-671 Migration 030304 developmental biology 0303 health sciences Matrigel Mammary tumor lcsh:Cytology Cell growth RNA sequencing miR-200 lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell biology Claudin‐low breast cancer MRNA Sequencing Oncology 030220 oncology & carcinogenesis Primary Research |
Zdroj: | Cancer Cell International, Vol 21, Iss 1, Pp 1-16 (2021) Cancer Cell International |
ISSN: | 1475-2867 |
Popis: | Background MicroRNAs are a class of non-coding RNAs that regulate gene expression through binding to mRNAs and preventing their translation. One family of microRNAs known as the miR-200 family is an important regulator of epithelial identity. The miR-200 family consists of five members expressed in two distinct clusters; the miR-200c/141 cluster and the miR-200b/200a/429 cluster. We have found that murine and human mammary tumor cells with claudin-low characteristics are associated with very low levels of all five miR-200s. Methods To determine the impact of miR-200s on claudin-low mammary tumor cells, the miR-200c/141 cluster and the miR-200b/200a/429 cluster were stably re-expressed in murine (RJ423) and human (MDA-MB-231) claudin-low mammary tumor cells. Cell proliferation and migration were assessed using BrdU incorporation and transwell migration across Matrigel coated inserts, respectively. miRNA sequencing and RNA sequencing were performed to explore miRNAs and mRNAs regulated by miR-200 re-expression while Enrichr-based pathway analysis was utilized to identify cellular functions modified by miR-200s. Results Re-expression of the miR-200s in murine and human claudin-low mammary tumor cells partially restored an epithelial cell morphology and significantly inhibited proliferation and cell invasion in vitro. miRNA sequencing and mRNA sequencing revealed that re-expression of miR-200s altered the expression of other microRNAs and genes regulated by SUZ12 providing insight into the complexity of miR-200 function. SUZ12 is a member of the polycomb repressor complex 2 that suppresses gene expression through methylating histone H3 at lysine 27. Flow cytometry confirmed that re-expression of miR-200s increased histone H3 methylation at lysine 27. Conclusions Re-expression of miR-200s in claudin-low mammary tumor cells alters cell morphology and reduces proliferation and invasion, an effect potentially mediated by SUZ12-regulated genes and other microRNAs. |
Databáze: | OpenAIRE |
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