shRNA knockdown of DNA helicase ERCC6L expression inhibits human breast cancer growth

Liu,Juan; Sun,Jing; Zhang,Qian; Zeng,Zhaochong

doi:10.3892/mmr.2018.9317

shRNA knockdown of DNA helicase ERCC6L expression inhibits human breast cancer growth

Authors:
- Juan Liu
- Jing Sun
- Qian Zhang
- Zhaochong Zeng
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Affiliations: Department of Radiotherapy, Zhongshan Hospital, Fudan University, Xuhui, Shanghai 200032, P.R. China
Published online on: July 25, 2018 https://doi.org/10.3892/mmr.2018.9317
Pages: 3490-3496

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Abstract

Breast cancer is a heterogeneous disease with a high degree of diversity with regards to tumor histological stage and molecular subtypes. These heterogeneous characteristics determine the risk of disease progression and therapeutic resistance. Understanding tumor heterogeneity is of primary concern to identify and develop novel and specific potential targets for diagnosis and therapy. The present study analyzed 106 paired breast cancer tissues from The Cancer Genome Atlas and demonstrated that excision repair cross‑complementation group 6 like (ERCC6L), a newly discovered DNA helicase, was overexpressed in 91.51% (97/106), unchanged in 7.54% (8/106) and decreased in 0.94% (1/106) of breast cancer samples. A short hairpin RNA ERCC6L lentivirus was constructed to investigate the role of ERCC6LR in cancer. First, a Celigo Image Cytometry system was used to detect MDA‑MB‑231 cell growth number following transfection with shERCC6L‑lentivirus or NC‑lentivirus and it was identified that the growth number of fluorescent MDA‑MB‑231 cells post‑transduction with shERCC6L‑lentivirus was decreased compared with the cells transduced with NC‑lentivirus. Then, the effect of knockdown of ERCC6L expression on the cell cycle distribution and apoptosis was to analyzed using fluorescence‑activated cell sorting (FACS). The FACS data demonstrated that knockdown of ERCC6L expression levels in MDA‑MB‑231 cells significantly increased S phase population but decreased the G1 and G2/M phase populations compared with the NC group. The apoptosis rate of MDA‑MB‑231 cells post‑transduction with shERCC6L‑lentivirus for 5 days was increased to 12.16±0.146% compared with the negative control rate (4.86±0.204%). These functional studies demonstrated that knockdown of ERCC6L expression levels in MDA‑MB‑231 cells significantly inhibited breast cancer cell proliferation, disturbed cell cycle distribution and induced apoptosis in vitro. These findings suggested that ERCC6L, which is highly expressed in breast cancer, acts as an oncogene, is involved in breast cancer development and may serve as a novel molecular target for the treatment of breast cancer.

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