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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4667818
- author
- Achari, Chandrani
LU
; Winslow, Sofia
LU
; Ceder, Yvonne
LU
and Larsson, Christer
LU
- organization
- publishing date
- 2014
- 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
- article number
- 538
- publisher
- BioMed Central (BMC)
- external identifiers
-
- wos:000339971500001
- scopus:84904779571
- pmid:25064703
- 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
- 2016-04-01 15:00:58
- date last changed
- 2022-04-22 06:20:26
@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.}},
author = {{Achari, Chandrani and Winslow, Sofia and Ceder, Yvonne and Larsson, Christer}},
issn = {{1471-2407}},
keywords = {{Breast cancer cells; miRNA-34c; CDC23; PKC alpha; Cell cycle arrest}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Cancer}},
title = {{Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells}},
url = {{https://lup.lub.lu.se/search/files/4297973/5277038}},
doi = {{10.1186/1471-2407-14-538}},
volume = {{14}},
year = {{2014}},
}