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

Abstract

BackgroundMicroRNA-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.MethodsData 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.ResultsTCGA 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.ConclusionsTogether, our results support the role of miR-34c as a tumor suppressor miRNA also in breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-538) contains supplementary material, which is available to authorized users.

Circulating microRNA-34 family low expression correlates with poor prognosis in patients with non-small cell lung cancer

“…Dysregulated expressions of miR-34 are observed in some carcinomas, such as colorectal cancer, breast cancer or even lung cancer (13)(14)(15). Particularly, aberrant miR-34b/c expressions have been reported to involve into the prognosis of small cell lung cancer (SCLC) and it could be a potential therapeutic target in SCLC patients (16).…”

miRNA-34c inhibits myoblasts proliferation by targeting YY1

“…14 It can inhibit the development of various cancers including osteosarcoma, lung cancer, uveal melanoma, prostate cancer, laryngeal carcinoma, breast cancer, and gastric cancer. [15][16][17][18][19][20][21] Previous studies show that sperm-borne miR-34c is important for the first cleavage division by Bcl -2. 22 It also modulates male germ cell development.…”

Pien Tze Huang inhibits the proliferation of colorectal cancer cells by increasing the expression of miR-34c-5p

“…The miR-34 family (miR-34a, miR-34b and miR-34c) has been shown to exhibit antiproliferative and pro-apoptotic functions (2), in which miR-34c has an important role in the development of various malignancies, including neuroblastoma, and breast, lung and colorectal cancer (CRC) (3)(4)(5)(6). miR-34c has two identified mature miRNAs: miR-34c-3p and miR-34c-5p.…”