KIF2C exerts an oncogenic role in nonsmall cell lung cancer and is negatively regulated by miR-325-3p
KIF2C exerts an oncogenic role in nonsmall cell lung cancer and is negatively regulated by miR-325-3p
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DOI：
10.1002/cbf.3420
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发表时间：
2019-07-22
影响因子：
3.6
通讯作者：
Sun, Butong
中科院分区：
文献类型：
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作者：
Gan, Huizhu;Lin, Lin;Sun, Butong
非小细胞肺癌(NSCLC)是全球癌症相关死亡的主要原因之一。Kinesin家族成员2C(KIF2C)是微管解聚、双极纺锤体形成和染色体分离的调节因子，已有报道在肿瘤生物学中发挥作用，但其在非小细胞肺癌中的作用尚不清楚。本研究旨在探讨KIF2C在非小细胞肺癌中的表达及功能。我们的结果表明KIF2C在非小细胞肺癌组织和细胞系中表达上调。KIF2C在非小细胞肺癌组织中的高表达与T分期高(0.0078)、分化程度差(0.0049)和淋巴结转移(P<；.0001)显著相关。我们还证明，KIF2C的高表达预示着患者预后较差。KIF2C基因敲除后，NSCLC细胞的增殖和转移受到抑制。荧光素酶报告基因分析表明，KIF2C是miR-325-3p的靶基因，而miR-325-3p被认为是非小细胞肺癌的肿瘤抑制基因。总之，本研究证实了KIF2C在非小细胞肺癌中的致癌作用，并部分阐明了其高表达的机制。我们的发现为了解NSCLC进展的机制提供了有用的见解，并为新的治疗策略提供了线索。
Nonsmall cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide. Kinesin family member 2C (KIF2C), a modulator in microtubule depolymerization, bipolar spindle formation, and chromosome segregation, has been reported to take roles in cancer biology, but its role in NSCLC remains unclear. This study was intended to investigate the expression and function of KIF2C in NSCLC. Our results demonstrated that KIF2C was up-regulated in NSCLC tissues and cell lines. The high expression of KIF2C in NSCLC tissues was significantly correlated with higher T stage (0.0078), worse differentiation status (0.0049), and lymph node metastasis (P < .0001). We also proved that the high expression level of KIF2C predicted worse prognosis of the patients. After knockdown of KIF2C, the proliferation and metastasis of NSCLC cells were inhibited. Luciferase reporter assay suggested that KIF2C was a target gene of miR-325-3p, which was reported to be a tumour suppressor in NSCLC. In conclusion, this study proved an oncogenic role of KIF2C in NSCLC and partly clarified the mechanism of its high expression. Our findings provided a useful insight into the mechanism of NSCLC progression and offered clues to novel therapy strategies.