NUCKS1 Promotes Proliferation, Invasion and Migration of Non-Small Cell Lung Cancer by Upregulating CDK1 Expression

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Dec 31

PMID 33380837

Citations 18

Authors

Shufen Zhao

Baiyao Wang

Yanning Ma

Junjie Kuang

Jiyun Liang

Yawei Yuan

Affiliations

Soon will be listed here.

Abstract

Background: Non-small cell lung cancer (NSCLC) is a predominant type of lung cancer with a high mortality rate.

Objective: The aim of this study is to investigate the roles of nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) in NSCLC and to identify the potential mechanisms.

Materials And Methods: The expression of NUCKS1 in several NSCLC cells was detected firstly. Then, NUCKS1 was overexpressed or silenced in both A549 and NCI-H460 cells, where cell proliferation, invasion and migration were, respectively, determined, using CCK-8, colony formation assay, transwell and wound healing assays. Cell cycle analysis was performed, and the expression-associated proteins were detected by Western blotting. Subsequently, NCI-H460 cells with NUCKS1 overexpression for the subsequent tumor-bearing experiment. And the NUCKS1 expression in tumor tissues was measured by means of immunohistochemistry and Western blotting. Additionally, the STRING database predicted that Cyclin-Dependent Kinase 1 (CDK1) would bind to NUSK1, which was verified by the co-immunoprecipitation assay. Then, CDK1 was silenced by transfection with short hairpin RNA (shRNA)-CDK-1 or by exposure to CDK1 inhibitor p2767-00. And the biological characteristics of proliferation, invasion and migration were examined.

Results: Results indicated that NUCKS1 was overly expressed in NSCLC cells, and its overexpression promoted proliferation, invasion and migration of both A549 and NCI-H460 cells while NUCKS1 knockdown displayed the opposite effects. Moreover, the results of the xenograft experiments revealed that NUCKS1-upregulation promoted the tumor growth. Furthermore, the immunoprecipitation assay verified CDK1's interaction with NUCKS1, and CDK1 knockdown alleviates the impact of NUCKS1 overexpression on NSCLC cell proliferation, invasion and migration.

Conclusion: Taken together, these findings demonstrated that NUCKS1 promotes proliferation, invasion and migration of NSCLC by upregulating CDK1, providing a novel putative target for the clinical treatment of NSCLC.

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References

ostvold A, Norum J, Mathiesen S, Wanvik B, Sefland I, Grundt K . Molecular cloning of a mammalian nuclear phosphoprotein NUCKS, which serves as a substrate for Cdk1 in vivo. Eur J Biochem. 2001; 268(8):2430-40. DOI: 10.1046/j.1432-1327.2001.02120.x. View

Reck M, Rabe K . Precision Diagnosis and Treatment for Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(9):849-861. DOI: 10.1056/NEJMra1703413. View

Huang Y, Kang W, Ma Z, Liu Y, Zhou L, Yu J . NUCKS1 promotes gastric cancer cell aggressiveness by upregulating IGF-1R and subsequently activating the PI3K/Akt/mTOR signaling pathway. Carcinogenesis. 2018; 40(2):370-379. DOI: 10.1093/carcin/bgy142. View

Liu Y, Li L, Wang X, Wang P, Wang Z . LncRNA TONSL-AS1 regulates miR-490-3p/CDK1 to affect ovarian epithelial carcinoma cell proliferation. J Ovarian Res. 2020; 13(1):60. PMC: 7229583. DOI: 10.1186/s13048-020-00657-0. View

Wang B, Hua P, Zhao B, Li J, Zhang Y . Circular RNA circDLGAP4 is involved in lung cancer development through modulating microRNA-143/CDK1 axis. Cell Cycle. 2020; 19(16):2007-2017. PMC: 7469555. DOI: 10.1080/15384101.2020.1786649. View

Tian Y, Zhang N, Chen S, Ma Y, Liu Y . The long non-coding RNA LSINCT5 promotes malignancy in non-small cell lung cancer by stabilizing HMGA2. Cell Cycle. 2018; 17(10):1188-1198. PMC: 6110604. DOI: 10.1080/15384101.2018.1467675. View

Drosos Y, Kouloukoussa M, Ostvold A, Grundt K, Goutas N, Vlachodimitropoulos D . NUCKS overexpression in breast cancer. Cancer Cell Int. 2009; 9:19. PMC: 2743642. DOI: 10.1186/1475-2867-9-19. View

Tian H, Zhou C, Yang J, Li J, Gong Z . Long and short noncoding RNAs in lung cancer precision medicine: Opportunities and challenges. Tumour Biol. 2017; 39(4):1010428317697578. DOI: 10.1177/1010428317697578. View

Zhao Y, Ye X, Chen R, Gao Q, Zhao D, Ling C . Sirtuin 7 promotes non‑small cell lung cancer progression by facilitating G1/S phase and epithelial‑mesenchymal transition and activating AKT and ERK1/2 signaling. Oncol Rep. 2020; 44(3):959-972. PMC: 7388485. DOI: 10.3892/or.2020.7672. View

10.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

11.

Kikuchi A, Ishikawa T, Mogushi K, Ishiguro M, Iida S, Mizushima H . Identification of NUCKS1 as a colorectal cancer prognostic marker through integrated expression and copy number analysis. Int J Cancer. 2012; 132(10):2295-302. DOI: 10.1002/ijc.27911. View

12.

Hao H, Zhou Z, Li S, Maquilan G, Folkert M, Iyengar P . Shell feature: a new radiomics descriptor for predicting distant failure after radiotherapy in non-small cell lung cancer and cervix cancer. Phys Med Biol. 2018; 63(9):095007. PMC: 5963260. DOI: 10.1088/1361-6560/aabb5e. View

13.

Schaner M, Ross D, Ciaravino G, Sorlie T, Troyanskaya O, Diehn M . Gene expression patterns in ovarian carcinomas. Mol Biol Cell. 2003; 14(11):4376-86. PMC: 266758. DOI: 10.1091/mbc.e03-05-0279. View

14.

Zhang L, Peng R, Sun Y, Wang J, Chong X, Zhang Z . Identification of key genes in non-small cell lung cancer by bioinformatics analysis. PeerJ. 2019; 7:e8215. PMC: 6911687. DOI: 10.7717/peerj.8215. View

15.

Wang X, Zhang H, Jiao K, Zhao C, Liu H, Meng Q . Effect of miR-205 on proliferation and migration of thyroid cancer cells by targeting CCNB2 and the mechanism. Oncol Lett. 2020; 19(3):2568-2574. PMC: 7039153. DOI: 10.3892/ol.2020.11275. View

16.

Yang F, Yan Y, Yang Y, Hong X, Wang M, Yang Z . MiR-210 in exosomes derived from CAFs promotes non-small cell lung cancer migration and invasion through PTEN/PI3K/AKT pathway. Cell Signal. 2020; 73:109675. DOI: 10.1016/j.cellsig.2020.109675. View

17.

Grana X, Reddy E . Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene. 1995; 11(2):211-9. View

18.

El-Aarag S, Mahmoud A, Hashem M, Abd Elkader H, Hemeida A, ElHefnawi M . In silico identification of potential key regulatory factors in smoking-induced lung cancer. BMC Med Genomics. 2017; 10(1):40. PMC: 5463402. DOI: 10.1186/s12920-017-0284-z. View

19.

Shen H, Wang L, Ge X, Jiang C, Shi Z, Li D . MicroRNA-137 inhibits tumor growth and sensitizes chemosensitivity to paclitaxel and cisplatin in lung cancer. Oncotarget. 2016; 7(15):20728-42. PMC: 4991488. DOI: 10.18632/oncotarget.8011. View

20.

Tang X, Zhang D, Jia L, Ji W, Zhao Y . lncRNA AFAP1-AS1 Promotes Migration and Invasion of Non-Small Cell Lung Cancer via Up-Regulating IRF7 and the RIG-I-Like Receptor Signaling Pathway. Cell Physiol Biochem. 2018; 50(1):179-195. DOI: 10.1159/000493967. View