STIP overexpression confers oncogenic potential to human non-small cell lung cancer cells by regulating cell cycle and apoptosis.
STIP overexpression confers oncogenic potential to human non-small cell lung cancer cells by regulating cell cycle and apoptosis.
复制标题
STIP 过表达通过调节细胞周期和细胞凋亡赋予人类非小细胞肺癌细胞致癌潜力。
DOI：
10.1111/jcmm.12670
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发表时间：
2015-12
影响因子：
5.3
通讯作者：
Liu J
中科院分区：
文献类型：
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作者：
Tang Y;Yan G;Song X;Wu K;Li Z;Yang C;Deng T;Sun Y;Hu X;Yang C;Bai H;Li H;Tan W;Ye M;Liu J
Sip1/tuftelin相互作用蛋白（STIP）是一种多结构域核蛋白，是与剪接体相关的新因子，但其在癌症中的作用和分子功能尚不清楚。在这项研究中，我们首次发现，与邻近的正常肺组织相比，STIP在非小细胞肺癌（NSCLC）组织中过表达。内源性STIP的缺失在体外和体内抑制NSCLC细胞增殖，引起细胞周期阻滞，诱导细胞凋亡。细胞周期阻滞在G2/M期与细胞周期蛋白B1 - CDK1（细胞周期蛋白依赖激酶1）复合物的表达和活性相关。我们还提供证据表明，STIP敲低可通过激活caspase‐9和caspase‐3以及改变Bcl‐2/Bax表达比诱导细胞凋亡。RNA测序数据表明，MAPK丝裂原活化蛋白激酶、Wnt、PI3K/AKT和NF - κB（活化B细胞的核因子κ轻链增强子）信号通路可能参与了STIP介导的肿瘤调节。总之，这些结果表明STIP可能是一种新的潜在的非小细胞肺癌诊断和治疗靶点。
Sip1/tuftelin‐interacting protein (STIP), a multidomain nuclear protein, is a novel factor associated with the spliceosome, yet its role and molecular function in cancer remain unknown. In this study, we show, for the first time, that STIP is overexpressed in non‐small cell lung cancer (NSCLC) tissues compared to adjacent normal lung tissues. The depletion of endogenous STIP inhibited NSCLC cell proliferation in vitro and in vivo, caused cell cycle arrest and induced apoptosis. Cell cycle arrest at the G2/M phase was associated with the expression and activity of the cyclin B1‐CDK1 (cyclin‐dependent kinase 1) complex. We also provide evidence that STIP knockdown induced apoptosis by activating both caspase‐9 and caspase‐3 and by altering the Bcl‐2/Bax expression ratio. RNA sequencing data indicated that the MAPK mitogen‐activated protein kinases, Wnt, PI3K/AKT, and NF‐κB (nuclear factor kappa‐light‐chain‐enhancer of activated B cells) signalling pathways might be involved in STIP‐mediated tumour regulation. Collectively, these results suggest that STIP may be a novel potential diagnostic and therapeutic target for NSCLC.