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Article

CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma

  • Authors:
    • Hanxu Yu
    • Jun Yao
    • Mingyu Du
    • Jinjun Ye
    • Xia He
    • Li Yin
  • View Affiliations / Copyright

    Affiliations: Department of Radiotherapy, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210000, P.R. China, Department of Radiotherapy, Yancheng Second People's Hospital, Yancheng, Jiangsu 22400, P.R. China
  • Pages: 542-548
    |
    Published online on: November 11, 2019
       https://doi.org/10.3892/ol.2019.11077
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Abstract

In China, esophageal squamous cell carcinoma (ESCC), capable of direct invasion and early metastasis, exhibits high mortality. Identification of the molecular basis driving ESCC progression and development of new diagnostic biomarkers are urgently needed. Cyclin‑dependent kinase inhibitor 3 (CDKN3) performs crucial roles in the modulation of tumor development. The present study aimed to explore the functions and underlying mechanism of CDKN3 in regulating ESCC cell proliferation and invasion. The expression levels of CDKN3 in ESCC cells were evaluated by reverse transcription‑quantitative PCR. Cell counting kit‑8 and colony forming assays were used to evaluate cell viability. Wound‑healing assay was performed to explore cell migration. Transwell invasion analysis was conducted to investigate the invasive capacity of ESCC cells. Protein levels were detected by western blot assay. The results demonstrated that the expression of CDKN3 was significantly upregulated in ESCC tissues, as predicted using the UALCAN and Gene Expression Omnibus databases. PCR and western blot assays confirmed that CDKN3 was upregulated in ESCC cell lines. Functional assays revealed that CDKN3 knockdown with small interfering RNA decreased the ability of ESCC cells to proliferate, invade and migrate and suppressed G1/S transition. Further mechanistic analyses demonstrated that CDKN3 promoted cell proliferation and invasion by activating the AKT signaling pathway in ESCC cells. To the best of our knowledge, the present study is the first to identify the functions of CDKN3 in ESCC and provide evidence that CDKN3 regulates tumor progression by activating the AKT signaling pathway. Therefore, CDKN3 may serve as a potential effective therapeutic target for ESCC treatment.
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1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Siegel RL, Miller KD and Jemal A: Cancer statistics. 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Zeng H, Zheng R, Zhang S, Zuo T, Xia C, Zou X and Chen W: Esophageal cancer statistics in China, 2011: Estimates based on 177 cancer registries. Thorac Cancer. 7:232–237. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Pennathur A, Gibson MK, Jobe BA and Luketich JD: Oesophageal carcinoma. Lancet. 381:400–412. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Zhang W, Li H, Chen X, Su M, Lin R and Zou C: Phase II study of concurrent chemoradiotherapy with a modified target volumes delineation method for inoperable oesophagealcancer patients. Br J Radiol. 90:201703282017. View Article : Google Scholar : PubMed/NCBI

7 

Lagergren J, Smyth E, Cunningham D and Lagergren P: Oesophageal cancer. Lancet. 390:2383–2396. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Cress WD, Yu P and Wu J: Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3 gene in human cancer. Int J Biochem Cell Biol. 91:98–101. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Liu D, Zhang J, Wu Y, Shi G, Yuan H, Lu Z, Zhu Q, Wu P, Lu C, Guo F, et al: YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway. Int J Cancer. 142:1392–1404. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Yu C, Cao H, He X, Sun P, Feng Y, Chen L and Gong H: Cyclin-dependent kinase inhibitor 3 (CDKN3) plays a critical role in prostate cancer via regulating cell cycle and DNA replication signaling. Biomed Pharmacother. 96:1109–1118. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Nalepa G, Barnholtz-Sloan J, Enzor R, Dey D, He Y, Gehlhausen JR, Lehmann AS, Park SJ, Yang Y, Yang X, et al: The tumor suppressor CDKN3 controls mitosis. J Cell Biol. 201:997–1012. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Song H, Hanlon N, Brown NR, Noble ME, Johnson LN and Barford D: Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2. Mol Cell. 7:615–626. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Yeh CT, Lu SC, Chao CH and Chao ML: Abolishment of the interaction between cyclin-dependent kinase 2 and Cdk-associated protein phosphatase by a truncated KAP mutant. Biochem Biophys Res Commun. 305:311–314. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Wang L, Sun L, Huang J and Jiang M: Cyclin-dependent kinase inhibitor 3 (CDKN3) novel cell cycle computational network between human non-malignancy associated hepatitis/cirrhosis and hepatocellular carcinoma (HCC) transformation. Cell Prolif. 44:291–299. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Barrón EV, Roman-Bassaure E, Sánchez-Sandoval AL, Espinosa AM, Guardado-Estrada M, Medina I, Juárez E, Alfaro A, Bermúdez M, Zamora R, et al: CDKN3 mRNA as a biomarker for survival and therapeutic target in cervical cancer. PLoS One. 10:e01373972015. View Article : Google Scholar : PubMed/NCBI

16 

Zang X, Chen M, Zhou Y, Xiao G, Xie Y and Wang X: Identifying CDKN3 gene expression as a prognostic biomarker in lung adenocarcinoma via meta-analysis. Cancer Inform. 14 (Suppl 2):S183–S191. 2015.

17 

Wang H, Chen H, Zhou H, Yu W and Lu Z: Cyclin-dependent kinase inhibitor 3 promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting p27. Oncol Res. 25:1431–1440. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Deng M, Wang J, Chen Y, Zhang L, Xie G, Liu Q, Zhang T, Yuan P and Liu D: Silencing cyclin-dependent kinase inhibitor 3 inhibits the migration of breast cancer cell lines. Mol Med Rep. 14:1523–1530. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Xu CQ, Zhu ST, Wang M, Guo SL, Sun XJ, Cheng R, Xing J, Wang WH, Shao LL and Zhang ST: Pathway analysis of differentially expressed genes in human esophageal squamous cell carcinoma. Eur Rev Med Pharmacol Sci. 19:1652–1661. 2015.PubMed/NCBI

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BVSK and Varambally S: UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 19:649–658. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Hu N, Clifford RJ, Yang HH, Wang C, Goldstein AM, Ding T, Taylor PR and Lee MP: Genome wide analysis of DNA copy number neutral loss of heterozygosity (CNNLOH) and its relation to gene expression in esophageal squamous cell carcinoma. BMC Genomics. 11:5762010. View Article : Google Scholar : PubMed/NCBI

23 

Chen YK, Tung CW, Lee JY, Hung YC, Lee CH, Chou SH, Lin HS, Wu MT and Wu IC: Plasma matrix metalloproteinase 1 improves the detection and survival prediction of esophageal squamous cell carcinoma. Sci Rep. 6:300572016. View Article : Google Scholar : PubMed/NCBI

24 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Lai MW, Chen TC, Pang ST and Yeh CT: Overexpression of cyclin-dependent kinase-associated protein phosphatase enhances cell proliferation in renal cancer cells. Urol Oncol. 30:871–878. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Chang SL, Chen TJ, Lee YE, Lee SW, Lin LC and He HL: CDKN3 expression is an independent prognostic factor and associated with advanced tumor stage in nasopharyngeal carcinoma. Int J Med Sci. 15:992–998. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Li Y, Ji S, Fu LY, Jiang T, Wu D and Meng FD: Knockdown of Cyclin-dependent kinase inhibitor 3 inhibits proliferation and invasion in human gastric cancer cells. Oncol Res. 25:721–731. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Dai W, Miao H, Fang S, Fang T, Chen N and Li M: CDKN3 expression is negatively associated with pathological tumor stage and CDKN3 inhibition promotes cell survival in hepatocellular carcinoma. Mol Med Rep. 14:1509–1514. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Wang J, Che W, Wang W, Su G, Zhen T and Jiang Z: CDKN3 promotes tumor progression and confers cisplatin resistance via RAD51 in esophageal cancer. Cancer Manag Res. 11:3253–3264. 2019. View Article : Google Scholar : PubMed/NCBI

30 

Liu J, Min L, Zhu S, Guo Q, Li H, Zhang Z, Zhao Y, Xu C and Zhang S: Cyclin-dependent kinase inhibitor 3 promoted cell proliferation by driving cell cycle from G1 to S phase in esophageal squamous cell carcinoma. J Cancer. 10:1915–1922. 2019. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yu H, Yao J, Du M, Ye J, He X and Yin L: CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma. Oncol Lett 19: 542-548, 2020.
APA
Yu, H., Yao, J., Du, M., Ye, J., He, X., & Yin, L. (2020). CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma. Oncology Letters, 19, 542-548. https://doi.org/10.3892/ol.2019.11077
MLA
Yu, H., Yao, J., Du, M., Ye, J., He, X., Yin, L."CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma". Oncology Letters 19.1 (2020): 542-548.
Chicago
Yu, H., Yao, J., Du, M., Ye, J., He, X., Yin, L."CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma". Oncology Letters 19, no. 1 (2020): 542-548. https://doi.org/10.3892/ol.2019.11077
Copy and paste a formatted citation
x
Spandidos Publications style
Yu H, Yao J, Du M, Ye J, He X and Yin L: CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma. Oncol Lett 19: 542-548, 2020.
APA
Yu, H., Yao, J., Du, M., Ye, J., He, X., & Yin, L. (2020). CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma. Oncology Letters, 19, 542-548. https://doi.org/10.3892/ol.2019.11077
MLA
Yu, H., Yao, J., Du, M., Ye, J., He, X., Yin, L."CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma". Oncology Letters 19.1 (2020): 542-548.
Chicago
Yu, H., Yao, J., Du, M., Ye, J., He, X., Yin, L."CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma". Oncology Letters 19, no. 1 (2020): 542-548. https://doi.org/10.3892/ol.2019.11077
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