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Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells

Achari, Chandrani LU ; Winslow, Sofia LU ; Ceder, Yvonne LU and Larsson, Christer LU (2014) In BMC Cancer 14.
Abstract
Background: MicroRNA-34 is a family of three miRNAs that have been reported to function as tumor suppressor miRNAs and show decreased expression in various cancers. Here, we examine functions of miR-34c in basal-like breast cancer cells. Methods: Data from The Cancer Genome Atlas (TCGA) were used for evaluation of expression in primary breast cancers. Cellular processes affected by miR-34c were investigated by thymidine incorporation, Annexin V-assays and cell cycle analysis using breast cancer cell lines. Effects on potential targets were analyzed with qPCR and Western blot. Results: TCGA data revealed that miR-34c was expressed at lower levels in basal-like breast cancer tumors and low expression was associated with poor prognosis.... (More)
Background: MicroRNA-34 is a family of three miRNAs that have been reported to function as tumor suppressor miRNAs and show decreased expression in various cancers. Here, we examine functions of miR-34c in basal-like breast cancer cells. Methods: Data from The Cancer Genome Atlas (TCGA) were used for evaluation of expression in primary breast cancers. Cellular processes affected by miR-34c were investigated by thymidine incorporation, Annexin V-assays and cell cycle analysis using breast cancer cell lines. Effects on potential targets were analyzed with qPCR and Western blot. Results: TCGA data revealed that miR-34c was expressed at lower levels in basal-like breast cancer tumors and low expression was associated with poor prognosis. Ectopic expression of miR-34c in basal-like breast cancer cell lines resulted in suppressed proliferation and increased cell death. Additionally, miR-34c influenced the cell cycle mainly by inducing an arrest in the G2/M phase. We found that expression levels of the known cell cycle-regulating miR-34 targets CCND1, CDK4 and CDK6, were downregulated upon miR-34c expression in breast cancer cell lines. In addition, the levels of CDC23, an important mediator in mitotic progression, were suppressed following miR-34c expression, and siRNAs targeting CDC23 mimicked the effect of miR-34c on G2/M arrest. However, protein levels of PRKCA, a predicted miR-34c target and a known regulator of breast cancer cell proliferation were not influenced by miR-34c. Conclusions: Together, our results support the role of miR-34c as a tumor suppressor miRNA also in breast cancer. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer cells, miRNA-34c, CDC23, PKC alpha, Cell cycle arrest
in
BMC Cancer
volume
14
publisher
BioMed Central
external identifiers
  • wos:000339971500001
  • scopus:84904779571
ISSN
1471-2407
DOI
10.1186/1471-2407-14-538
language
English
LU publication?
yes
id
6160050b-6f39-4035-ae66-222fa1fc3673 (old id 4667818)
date added to LUP
2014-10-01 07:24:19
date last changed
2017-10-22 04:27:37
@article{6160050b-6f39-4035-ae66-222fa1fc3673,
  abstract     = {Background: MicroRNA-34 is a family of three miRNAs that have been reported to function as tumor suppressor miRNAs and show decreased expression in various cancers. Here, we examine functions of miR-34c in basal-like breast cancer cells. Methods: Data from The Cancer Genome Atlas (TCGA) were used for evaluation of expression in primary breast cancers. Cellular processes affected by miR-34c were investigated by thymidine incorporation, Annexin V-assays and cell cycle analysis using breast cancer cell lines. Effects on potential targets were analyzed with qPCR and Western blot. Results: TCGA data revealed that miR-34c was expressed at lower levels in basal-like breast cancer tumors and low expression was associated with poor prognosis. Ectopic expression of miR-34c in basal-like breast cancer cell lines resulted in suppressed proliferation and increased cell death. Additionally, miR-34c influenced the cell cycle mainly by inducing an arrest in the G2/M phase. We found that expression levels of the known cell cycle-regulating miR-34 targets CCND1, CDK4 and CDK6, were downregulated upon miR-34c expression in breast cancer cell lines. In addition, the levels of CDC23, an important mediator in mitotic progression, were suppressed following miR-34c expression, and siRNAs targeting CDC23 mimicked the effect of miR-34c on G2/M arrest. However, protein levels of PRKCA, a predicted miR-34c target and a known regulator of breast cancer cell proliferation were not influenced by miR-34c. Conclusions: Together, our results support the role of miR-34c as a tumor suppressor miRNA also in breast cancer.},
  articleno    = {538},
  author       = {Achari, Chandrani and Winslow, Sofia and Ceder, Yvonne and Larsson, Christer},
  issn         = {1471-2407},
  keyword      = {Breast cancer cells,miRNA-34c,CDC23,PKC alpha,Cell cycle arrest},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Cancer},
  title        = {Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells},
  url          = {http://dx.doi.org/10.1186/1471-2407-14-538},
  volume       = {14},
  year         = {2014},
}