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KIF2C 在非小细胞肺癌中发挥致癌作用,受 miR-325-3p 的负调控。

KIF2C exerts an oncogenic role in nonsmall cell lung cancer and is negatively regulated by miR-325-3p.

机构信息

Department of Oncology, China-Japan Union Hospital of Jilin University, Changchun, China.

National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Cell Biochem Funct. 2019 Aug;37(6):424-431. doi: 10.1002/cbf.3420. Epub 2019 Jul 22.

DOI:10.1002/cbf.3420
PMID:31328811
Abstract

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.

摘要

非小细胞肺癌(NSCLC)是全球癌症相关死亡的主要原因之一。驱动蛋白家族成员 2C(KIF2C)是微管解聚、双极纺锤体形成和染色体分离的调节剂,据报道其在癌症生物学中发挥作用,但在 NSCLC 中的作用尚不清楚。本研究旨在探讨 KIF2C 在 NSCLC 中的表达和功能。我们的结果表明,KIF2C 在 NSCLC 组织和细胞系中上调。KIF2C 在 NSCLC 组织中的高表达与较高的 T 分期(0.0078)、较差的分化状态(0.0049)和淋巴结转移(P<.0001)显著相关。我们还证明,KIF2C 的高表达水平预测患者预后不良。敲低 KIF2C 后,NSCLC 细胞的增殖和转移受到抑制。荧光素酶报告基因检测表明,KIF2C 是 miR-325-3p 的靶基因,miR-325-3p 被报道在 NSCLC 中是一种肿瘤抑制因子。总之,本研究证明了 KIF2C 在 NSCLC 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 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。

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