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
Rok vydání: 2014
Předmět:
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