NEK2 is associated with poor prognosis of clear cell renal cell carcinoma and promotes tumor cell growth and metastasis

被引:5
|
作者
Feng, Xiaoli [1 ]
Jiang, Yang [2 ]
Cui, Yue [3 ]
Xu, Yingkun [4 ]
Zhang, Qi [5 ]
Xia, Qinghua [5 ]
Chen, Yougen [5 ]
机构
[1] Shandong Univ, Hosp 2, Cheeloo Coll Med, Dept Clin Lab, Jinan 250033, Shandong, Peoples R China
[2] Shandong Univ, Hosp 2, Cheeloo Coll Med, Dept Hematol, Jinan 250033, Shandong, Peoples R China
[3] Liaocheng Peoples Hosp, Dept Radiol, Liaocheng 252004, Shandong, Peoples R China
[4] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine & Breast Surg, Chongqing 400042, Peoples R China
[5] Shandong First Med Univ, Shandong Prov Hosp, Dept Urol, Jinan 250021, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
Never in Mitosis gene-A (NIMA)-related Kinase; 2 (NEK2); Clear cell renal cell carcinoma (ccRCC); Proliferation; Migration; Invasion; KINASE; SIRNA; GENE;
D O I
10.1016/j.gene.2022.147040
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Never in Mitosis gene-A (NIMA)-related Kinase 2 (NEK2) is a critical player in the mitotic processes. NEK2 is highly expressed in many kinds of human cancers and has been shown to participate in drug resistance, tumorigenesis, and tumor progression. However, the expression or function of NEK2 in clear cell renal cell carcinoma (ccRCC) has not yet been investigated.Methods: We used TCGA database to study the NEK2 expression in ccRCC. The expression of NEK2 in tumor tissues and adjacent tissues was examined by immunohistochemistry. We also analysed the correlation between NEK2 expression and clinical parameters of ccRCC. The mRNA and protein level of NEK2 expression were semi -quantified by qRT-PCR and western blotting analysis. Following NEK2 knockdown by RNA interference in Caki-1 cells, while NEK2 overexpression in A489 cells, CCK8 and transwell assay was used to confirm the prolifera-tion, migration and invasion, respectively. Finally, our in vivo study were carried out using nude mice to establish mouse model for kidney cancer.Results: We observed elevated expression of NEK2 both in ccRCC tumor tissues and cell lines. Together with clinical and pathological features, our analysis indicated a clear association of clinical outcomes between ccRCC patients with high and low NEK2 expression. Our in vitro studies demonstrated that NEK2 knockdown inhibits the proliferation, migration and invasion of Caki-1 cells, oppositely, overexpression of NEK2 promotes the pro-liferation, migration and invasion of A489 cells. In the end, our animal study demonstrated that deletion of NEK2 expression could impair tumor growth.Conclusion: Our data suggested that NEK2 was important in regulating ccRCC cell proliferation and metastasis, and indicated NEK2 as a potentially important target for the treatment of ccRCC.
引用
收藏
页数:8
相关论文
共 50 条
  • [1] Overexpression of NEK2 is correlated with poor prognosis in human clear cell renal cell carcinoma
    Wang, Chenfeng
    Huang, Yan
    Ma, Xin
    Wang, Baojun
    Zhang, Xu
    INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 2021, 35
  • [2] VCAN promotes clear cell renal cell carcinoma tumor progression and metastasis, and predicts poor prognosis
    Mitsui, Yozo
    Kato, Taku
    Maekawa, Shigekatsu
    Hashimoto, Yutaka
    Shiina, Marisa
    Sumida, Mitsuho Imai
    Wong, Ryan Kenji
    Yamamura, Soichiro
    Shahryari, Varahram
    Majid, Shahana
    Saini, Sharanjot
    Deng, Guoren
    Dahiya, Rajvir
    Nakajima, Koichi
    Tanaka, Yuichiro
    CANCER RESEARCH, 2017, 77
  • [3] Function of NEK2 in clear cell renal cell carcinoma and its effect on the tumor microenvironment
    Tang, Peng
    Zheng, Gangfu
    Xu, Congcong
    Yu, Nengfeng
    Du, Jiaqi
    Hu, Liqian
    Zhou, Zhan
    Zheng, Yichun
    MEDICINE, 2024, 103 (20) : E37939
  • [4] GENOMIC ALTERATIONS ASSOCIATED WITH METASTASIS AND POOR PROGNOSIS IN CLEAR CELL RENAL CELL CARCINOMA
    Sanjmyatav, Jimsgene
    Schwaenen, Carsten
    Wessendorf, Sven
    Kreuz, Markus
    Steiner, Thomas
    Wunderlich, Heiko
    Junker, Kerstin
    JOURNAL OF UROLOGY, 2010, 183 (04): : E243 - E243
  • [5] FABP5 is correlated with poor prognosis and promotes tumour cell growth and metastasis in clear cell renal cell carcinoma
    Wu, Guangzhen
    Xu, Yingkun
    Wang, Qifei
    Li, Jianyi
    Li, Lin
    Han, Chenglin
    Xia, Qinghua
    EUROPEAN JOURNAL OF PHARMACOLOGY, 2019, 862
  • [6] KRT8 upregulation promotes tumor metastasis and is predictive of a poor prognosis in clear cell renal cell carcinoma
    Tan, Hai-Song
    Jiang, Wei-Hua
    He, Yi
    Wang, De-Sheng
    Wu, Zhen-Jie
    Wu, Deng-Shuang
    Gao, Li
    Bao, Yi
    Shi, Jia-Zi
    Liu, Bing
    Ma, Li-Jun
    Wang, Lin-Hui
    ONCOTARGET, 2017, 8 (44) : 76189 - 76203
  • [7] Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma
    Heinzelmann, Joana
    Henning, Brenda
    Sanjmyatav, Jimsgene
    Posorski, Nicole
    Steiner, Thomas
    Wunderlich, Heiko
    Gajda, Mieczyslaw R.
    Junker, Kerstin
    WORLD JOURNAL OF UROLOGY, 2011, 29 (03) : 367 - 373
  • [8] Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma
    Joana Heinzelmann
    Brenda Henning
    Jimsgene Sanjmyatav
    Nicole Posorski
    Thomas Steiner
    Heiko Wunderlich
    Mieczyslaw R. Gajda
    Kerstin Junker
    World Journal of Urology, 2011, 29 : 367 - 373
  • [9] IDENTIFICATION OF GENOMIC ALTERATIONS ASSOCIATED WITH METASTASIS AND POOR PROGNOSIS IN CLEAR CELL RENAL CELL CARCINOMA
    Sanjmyatav, J.
    Schwaenen, C.
    Wessendorf, S.
    Kreuz, M.
    Gajda, M.
    Wunderlich, H.
    Junker, K.
    CELLULAR ONCOLOGY, 2010, 32 (03) : 190 - 191
  • [10] Decreased SATB2 expression is associated with metastasis and poor prognosis in human clear cell renal cell carcinoma
    Guo, Changcheng
    Xiong, Dabo
    Yao, Xudong
    Gu, Wenyu
    Zhang, Haimin
    Yang, Bin
    Peng, Bo
    Liu, Min
    Zheng, Junhua
    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY, 2015, 8 (04): : 3710 - 3718