Knocking down the expression of Aurora-A gene inhibits cell proliferation and induces G2/M phase arrest in human small cell lung cancer cells
Autor: | Ning Zhong, Jianzhong Jiang, Zhaoqing Xi, Xiaodong Wei, Shunbin Shi, Yuanhua Liu, Yimin Lu, Jinzhi Wang |
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Rok vydání: | 2014 |
Předmět: |
Cancer Research
Lung Neoplasms Cell cycle checkpoint Cell Apoptosis Biology medicine.disease_cause Cell Line Tumor medicine Humans RNA Small Interfering Aurora Kinase A Cell Proliferation Cell growth AURKA Gene General Medicine Cell cycle Small Cell Lung Carcinoma respiratory tract diseases Cell biology G2 Phase Cell Cycle Checkpoints Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Gene Knockdown Techniques Carcinogenesis A431 cells |
Zdroj: | Oncology Reports. 32:243-249 |
ISSN: | 1791-2431 1021-335X |
DOI: | 10.3892/or.2014.3194 |
Popis: | A hallmark of small cell lung cancer (SCLC) is frequent relapse characterized by newfound resistance to formerly efficacious chemotherapies. The prognosis for SCLC patients is particularly unfavorable. Aurora kinase A (AURKA), a member of the serine/threonine kinase family, is overexpressed across many types of human tumors. Recent studies have identified AURKA as an important factor in tumorigenesis, but little is known regarding its specific roles in SCLC. The aim of the present study was to establish the roles of AURKA in the molecular pathogenesis of human SCLC. In the present study, we constructed a lentiviral vector to express siRNA against AURKA (LV-AURKA siRNA). As we expected, the viral construct effectively suppressed the expression of the AURKA gene and protein in H446 and H1688 cell lines. Additionally, RNA interference of AURKA inhibited the colony formation and subsequent growth of H446 and H1688 cell lines by increasing the incidence of cell cycle arrest in the G2/M phase. Furthermore, suppression of AURKA by LV-AURKA siRNA also increased apoptosis of SCLC cells. A potential mechanism for the increase of apoptosis is the downregulation of Bcl-2 and upregulation of Bax. AURKA gene suppression may provide a novel, effective therapy for SCLC patients by inhibiting cell division and increasing the rate of apoptosis of SCLC cells. |
Databáze: | OpenAIRE |
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