SMC1A knockdown induces growth suppression of human lung adenocarcinoma cells through G1/S cell cycle phase arrest and apoptosis pathways in vitro

Zhang,Yi-Fan; Jiang,Rui; Li,Jin-Dong; Zhang,Xing-Yi; Zhao,Peng; He,Miao; Zhang,Hou-Zhong; Sun,Li-Ping; Shi,Dong-Lei; Zhang,Guang-Xin; Sun,Mei

doi:10.3892/ol.2013.1116

SMC1A knockdown induces growth suppression of human lung adenocarcinoma cells through G1/S cell cycle phase arrest and apoptosis pathways in vitro

Authors:
- Yi-Fan Zhang
- Rui Jiang
- Jin-Dong Li
- Xing-Yi Zhang
- Peng Zhao
- Miao He
- Hou-Zhong Zhang
- Li-Ping Sun
- Dong-Lei Shi
- Guang-Xin Zhang
- Mei Sun
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Affiliations: Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun 130041, P.R. China, Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China, Department of Anesthesia, The Second Hospital of Jilin University, Changchun 130041, P.R. China, Department of Pathology, The Second Hospital of Jilin University, Changchun 130041, P.R. China
Published online on: January 8, 2013 https://doi.org/10.3892/ol.2013.1116
Pages: 749-755

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Abstract

SMC1A (structural maintenance of chromosomes 1A), which encodes a structural subunit of the cohesin protein complex, is necessary for the process of sister chromatid cohesion during the cell cycle. Mutation and deregulation of SMC1A are highly relevant to diverse human diseases, including Cornelia de Lange syndrome and malignant carcinomas. In order to further investigate the role of SMC1A in the oncogenesis of lung cancer, SMC1A-specific short hairpin RNA (shRNA)-expressing lentivirus (Lv-shSMC1A) was constructed and used to infect A549 and H1299 cells. SMC1A mRNA and protein expression levels were downregulated in A549 and H1299 cells as demonstrated by real-time PCR and western blot assays. We found that SMC1A inhibition resulted in significantly impaired proliferation and colony formation as well as reduced invasiveness of tumor cells. Notably, Lv-shSMC1A-infected cancer cells exhibited a greater proportion of cells in the G0/G1 phase, but a lower proportion of S phase cells, compared to the parent or Lv-shCon infected cancer cells. Moreover, a greater proportion of sub-G1 apoptotic cells was observed in Lv-shSMC1A-infected cells. These results suggest that SMC1A is a novel proliferation regulator that promotes the growth of lung cancer cells, and that downregulation of SMC1A expression induces growth suppression of A549 and H1299 cells via G1/S cell cycle phase arrest and apoptosis pathways. Therefore, SMC1A may serve as a new molecular target for lung cancer therapy.

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