Downregulation of KPNA2 in non-small-cell lung cancer is associated with Oct4 expression.
Downregulation of KPNA2 in non-small-cell lung cancer is associated with Oct4 expression.
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DOI：
10.1186/1479-5876-11-232
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发表时间：
2013-09-26
影响因子：
7.4
通讯作者：
Jia XS
中科院分区：
文献类型：
--
作者：
Li XL;Jia LL;Shi MM;Li X;Li ZH;Li HF;Wang EH;Jia XS
Oct4是干细胞自我更新和分化的主要转录因子。为了实现其功能，它必须能够进入细胞核并留在那里影响转录。KPNA 2是核转运蛋白家族的一员，在核质转运中起核心作用。本研究旨在探讨Oct4和KPNA 2表达水平与非小细胞肺癌（NSCLC）患者临床病理特征和预后的关系。采用免疫组化法检测Oct4和KPNA2在NSCLC组织及癌旁肺组织中的表达情况。采用实时荧光定量聚合酶链反应（PCR）和蛋白质印迹法（Western blotting）检测肺癌细胞株Oct4和KPNA2的mRNA和蛋白质表达谱。小干扰RNA用于消减Oct4和KPNA 2表达。采用免疫荧光双标法检测KPNA 2基因敲减细胞中Oct4的表达。采用免疫共沉淀法检测Oct4与KPNA 2的相互作用。Oct4在102例肺癌组织中有29例（28.4%）过表达，与肺癌分化程度（P = 0.002）和TNM分期（P = 0.003）相关。KPNA2在102例肺癌中有56例（54.9%）过表达，与组织学（P = 0.001）和分化程度（P = 0.045）相关。Oct4和KPNA 2表达水平显著相关（P < 0.01）。Oct4和KPNA 2的表达与短的总生存期相关。此外，使用小干扰RNA消除Oct4和KPNA2表达抑制肺癌细胞系的增殖。实时聚合酶链反应和蛋白质印迹分析表明，减少KPNA 2表达显着降低mRNA和核蛋白水平的Oct4。免疫荧光双标分析显示，KPNA 2敲低细胞核Oct4信号显著降低。免疫共沉淀实验显示，KPNA 2与肺癌细胞系中的Oct4相互作用。Oct4和KPNA 2在NSCLC进展中起重要作用。Oct4的核定位可能是通过其与KPNA 2的相互作用来介导的。
Oct4 is a major transcription factor related to stem cell self-renewal and differentiation. To fulfill its functions, it must be able to enter the nucleus and remain there to affect transcription. KPNA2, a member of the karyopherin family, plays a central role in nucleocytoplasmic transport. The objective of the current study was to examine the association between Oct4 and KPNA2 expression levels with regard to both the clinicopathological characteristics and prognoses of patients with non-small-cell lung cancer (NSCLC). Immunohistochemistry was used to detect the expression profile of Oct4 and KPNA2 in NSCLC tissues and adjacent noncancerous lung tissues. Real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein expression profiles of Oct4 and KPNA2 in lung cancer cell lines. Small interfering RNAs were used to deplete Oct4 and KPNA2 expressions. Double immunofluorescence was used to detect Oct4 expression in KPNA2 knockdown cells. Co-immunoprecipitation was used to detect the interaction of Oct4 and KPNA2. Oct4 was overexpressed in 29 of 102 (28.4%) human lung cancer samples and correlated with differentiation (P = 0.002) and TNM stage (P = 0.003). KPNA2 was overexpressed in 56 of 102 (54.9%) human lung cancer samples and correlated with histology (P = 0.001) and differentiation (P = 0.045). Importantly, Oct4 and KPNA2 expression levels correlated significantly (P < 0.01). Expression of Oct4 and KPNA2 was associated with short overall survival. In addition, depleting Oct4 and KPNA2 expression using small interfering RNAs inhibited proliferation in lung cancer cell lines. Real-time polymerase chain reaction and western blotting analysis indicated that reduction of KPNA2 expression significantly reduced mRNA and nucleoprotein levels of Oct4. Double immunofluorescence analysis revealed that nuclear Oct4 signals were reduced significantly in KPNA2 knockdown cells. Co-immunoprecipitation experiments revealed that KPNA2 interacts with Oct4 in lung cancer cell lines. Oct4 and KPNA2 play an important role in NSCLC progression. Oct4 nuclear localization may be mediated by its interaction with KPNA2.
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影响因子：
8
作者：
Monk, M;Holding, C
通讯作者：
Holding, C
影响因子：
3.9
作者：
Gousias, K.;Becker, A. J.;Niehusmann, P.
通讯作者：
Niehusmann, P.
影响因子：
4.8
作者：
Pan, GJ;Qin, BM;Pei, DQ
通讯作者：
Pei, DQ
影响因子：
3.7
作者：
Chen, Yu-Chih;Hsu, Han-Shui;Chen, Yi-Wei;Tsai, Tung-Hu;How, Chorng-Kuang;Wang, Chien-Ying;Hung, Shih-Chieh;Chang, Yuh-Lih;Tsai, Ming-Long;Lee, Yi-Yen;Ku, Hung-Hai;Chiou, Shih-Hwa
通讯作者：
Chiou, Shih-Hwa
影响因子：
6.4
作者：
Wang, Chun-I.;Wang, Chih-Liang;Yu, Chia-Jung
通讯作者：
Yu, Chia-Jung