RNAi-mediated downregulation of cyclin Y to attenuate human breast cancer cell growth.

Abstract

Cyclin Y (CCNY) is a newly identified PFTK1 interacting protein and has been found to be associated with the proliferation and tumorigenesis of human non-small cell lung cancer. In the present study, we analyzed the expression levels of CCNY in 65 cases of breast cancer (BC) tissues and in four BC cell lines, BT-474, MDA-MB-231, T-47D and MCF-7. Lentivirus-mediated short hairpin RNA (shRNA) was employed to knock down CCNY expression in MCF-7 and MDA-MB-231 cells. The effects of CCNY depletion on cell growth were examined by MTT, colony formation and flow cytometry assays. The results showed that immunohistochemical expression of CCNY in tumor tissues is stronger than that in normal tissues. CCNY was also expressed in all four BC cells. The knockdown of CCNY resulted in a significant reduction in cell proliferation and colony formation ability. Cell cycle analysis showed that CCNY knockdown arrested MDA-MB‑231 cells in the G0/G1 phase. Furthermore, depletion of CCNY inhibited BC cell growth via the activation of Bad and GSK3β, as well as cleavages of PARP and caspase-3 in a p53-dependent manner. Therefore, we believe that CCNY has biological effect in BC development, and its inhibition via an RNA interference lentiviral system may provide a therapeutic option for BC.

• Authors: Feng Yan, Xiaoming Wang, Mingchen Zhu, Xiaoya Hu
• Journal: Oncology reports (Oncol Rep) Vol. 36 Issue 5 Pg. 2793-2799 (Nov 2016) ISSN: 1791-2431 [Electronic] Greece
• PMID: 27666310 (Publication Type: Journal Article)

Chemical References

• BAD protein, human
• Biomarkers, Tumor
• CCNY protein, human
• Cyclins
• RNA, Small Interfering
• TP53 protein, human
• Tumor Suppressor Protein p53
• bcl-Associated Death Protein
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Caspase 3

Topics

• Apoptosis (genetics)
• Biomarkers, Tumor (genetics, therapeutic use)
• Breast Neoplasms (genetics, pathology, therapy)
• Caspase 3 (biosynthesis, genetics)
• Cell Proliferation (genetics)
• Cyclins (genetics, therapeutic use)
• Female
• Gene Expression Regulation, Neoplastic
• Glycogen Synthase Kinase 3 beta (biosynthesis, genetics)
• Humans
• Lentivirus (genetics)
• MCF-7 Cells
• Poly (ADP-Ribose) Polymerase-1 (biosynthesis, genetics)
• RNA, Small Interfering (genetics, therapeutic use)
• Tumor Suppressor Protein p53 (genetics)
• bcl-Associated Death Protein (biosynthesis, genetics)