Knocking down the expression of Aurora-A gene inhibits cell proliferation and induces G2/M phase arrest in human small cell lung cancer cells.
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.
Department of Emergency, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Yimin
Y
Lu
Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210009, P.R. China.
Yuanhua
Y
Liu
Department of Geriatrics, People's Hospital of Yixing City, Yixing, Jiangsu 214200, P.R. China.
Jianzhong
J
Jiang
Department of Emergency, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Zhaoqing
Z
Xi
Department of Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu 215300, P.R. China.
Ning
N
Zhong
Department of Thoracic Surgery, Affiliated Wujiang Hospital of Nantong University, Suzhou, Jiangsu 215200, P.R. China.
Shunbin
S
Shi
Department of Cell Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
Jinzhi
J
Wang
Department of Thoracic Surgery, No. 101 Hospital of PLA, Wuxi, Jiangsu 214044, P.R. China.
Xiaodong
X
Wei
D017209:Apoptosis; D064096:Aurora Kinase A / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000201:enzymology / Q000473:pathology*
D034741:RNA, Small Interfering; D064096:Aurora Kinase A