KIF2A participates in the progression of hepatocellular carcinoma and angiogenesis by interacting with Notch1

Wu,Qi; Ren,Xuting; Chen,Yun; Jin,Ye; Zhan,Xiaobo; Liu,Changfeng; Zhang,Bing

doi:10.3892/etm.2022.11619

KIF2A participates in the progression of hepatocellular carcinoma and angiogenesis by interacting with Notch1

Authors:
- Qi Wu
- Xuting Ren
- Yun Chen
- Ye Jin
- Xiaobo Zhan
- Changfeng Liu
- Bing Zhang
View Affiliations

Affiliations: Department of General Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China, Department of Stomatology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China
Published online on: September 22, 2022 https://doi.org/10.3892/etm.2022.11619
Article Number: 683
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Kinesin family member 2A (KIF2A) serves a vital role in the development of hepatocellular carcinoma (HCC); however, the biological effect of KIF2A on the malignant progression of HCC remains unclear. Therefore, the present study was conducted to systematically determine the biological role of KIF2A in HCC and to better understand the molecular mechanism. The differences of KIF2A expression in HHL‑5 normal human hepatocytes and the HCC cell lines Li‑7, Huh7 and MHCC97 were assessed by reverse transcription‑quantitative PCR and western blotting analysis. Moreover, viability, proliferation, migration and invasion of HCC cells were assessed by performing CCK‑8, 5‑ethynyl‑2'‑deoxyuridine staining, wound healing and Transwell assays. Additionally, the tube formation assay was performed to evaluate angiogenesis of HUVECs incubated with the conditioned media of HCC cells in vitro. The interaction between KIF2A and Notch1 was analyzed through co‑immunoprecipitation assay. KIF2A was revealed to be highly expressed in HCC cells. KIF2A knockdown suppressed HCC cell proliferation, migration and invasion, and impaired in vitro angiogenesis. Furthermore, it was revealed that KIF2A interacted with Notch1 and positively regulated Notch1 expression. The suppressive effects of KIF2A knockdown on HCC cell proliferation, migration, invasion and in vitro angiogenesis were partially reversed by Notch1 overexpression. Overall, KIF2A may act as an oncogene in HCC via activation of the Notch1 signaling pathway.

View Figures

View References

1	Sivasudhan E, Blake N, Lu ZL, Meng J and Rong R: Dynamics of m6A RNA methylome on the hallmarks of hepatocellular carcinoma. Front Cell Dev Biol. 9(642443)2021.PubMed/NCBI View Article : Google Scholar
2	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021.PubMed/NCBI View Article : Google Scholar
3	Xu G, Zhang P, Liang H, Xu Y, Shen J, Wang W, Li M, Huang J, Ni C, Zhang X, et al: Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma. Cancer Cell Int. 21(212)2021.PubMed/NCBI View Article : Google Scholar
4	Yuan P, Mu J, Wang Z, Ma S, Da X, Song J, Zhang H, Yang L, Li J and Yang J: Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation. Cell Death Dis. 12(361)2021.PubMed/NCBI View Article : Google Scholar
5	Moodley S, Lian EY, Crupi MJF, Hyndman BD and Mulligan LM: RET isoform-specific interaction with scaffold protein Ezrin promotes cell migration and chemotaxis in lung adenocarcinoma. Lung Cancer. 142:123–131. 2020.PubMed/NCBI View Article : Google Scholar
6	Maia AF, Tanenbaum ME, Galli M, Lelieveld D, Egan DA, Gassmann R, Sunkel CE, van den Heuvel S and Medema RH: Genome-wide RNAi screen for synthetic lethal interactions with the C. elegans kinesin-5 homolog BMK-1. Sci Data. 2(150020)2015.PubMed/NCBI View Article : Google Scholar
7	Wang W, Zhang R, Wang X, Wang N, Zhao J, Wei Z, Xiang F and Wang C: Suppression of KIF3A inhibits triple negative breast cancer growth and metastasis by repressing Rb-E2F signaling and epithelial-mesenchymal transition. Cancer Sci. 111:1422–1434. 2020.PubMed/NCBI View Article : Google Scholar
8	Welburn JP and Cheeseman IM: The microtubule-binding protein Cep170 promotes the targeting of the kinesin-13 depolymerase Kif2b to the mitotic spindle. Mol Biol Cell. 23:4786–4795. 2012.PubMed/NCBI View Article : Google Scholar
9	Zhang X, Ma C, Wang Q, Liu J, Tian M, Yuan Y, Li X and Qu X: Role of KIF2A in the progression and metastasis of human glioma. Mol Med Rep. 13:1781–1787. 2016.PubMed/NCBI View Article : Google Scholar
10	Wang Z, Liu X, Liu X and Niu D: Long non-coding RNA BLACAT1 promotes the tumorigenesis of gastric cancer by sponging microRNA-149-5p and targeting KIF2A. Cancer Manag Res. 12:6629–6640. 2020.PubMed/NCBI View Article : Google Scholar
11	Wang YF, Li MY, Tang YF, Jia M, Liu Z and Li HQ: Circular RNA circEIF3I promotes papillary thyroid carcinoma progression through competitively binding to miR-149 and upregulating KIF2A expression. Am J Cancer Res. 10:1130–1139. 2020.PubMed/NCBI
12	Zhu Y, Ma C, Lv A and Kou C: Circular RNA circ_0010235 sponges miR-338-3p to play oncogenic role in proliferation, migration and invasion of non-small-cell lung cancer cells through modulating KIF2A. Ann Med. 53:693–706. 2021.PubMed/NCBI View Article : Google Scholar
13	Liu W, Xu C, Meng Q and Kang P: The clinical value of kinesin superfamily protein 2A in hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 45(101527)2021.PubMed/NCBI View Article : Google Scholar
14	Chen J, Li S, Zhou S, Cao S, Lou Y, Shen H, Yin J and Li G: Kinesin superfamily protein expression and its association with progression and prognosis in hepatocellular carcinoma. J Cancer Res Ther. 13:651–659. 2017.PubMed/NCBI View Article : Google Scholar
15	Capaccione KM and Pine SR: The notch signaling pathway as a mediator of tumor survival. Carcinogenesis. 34:1420–1430. 2013.PubMed/NCBI View Article : Google Scholar
16	Bazzoni R and Bentivegna A: Role of notch signaling pathway in glioblastoma pathogenesis. Cancers (Basel). 11(292)2019.PubMed/NCBI View Article : Google Scholar
17	Zhang L, Chen J, Yong J, Qiao L, Xu L and Liu C: An essential role of RNF187 in Notch1 mediated metastasis of hepatocellular carcinoma. J Exp Clin Cancer Res. 38(384)2019.PubMed/NCBI View Article : Google Scholar
18	Jue C, Lin C, Zhisheng Z, Yayun Q, Feng J, Min Z, Haibo W, Youyang S, Hisamitsu T, Shintaro I, et al: Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling. Oncotarget. 8:2501–2513. 2017.PubMed/NCBI View Article : Google Scholar
19	Huang Q, Li J, Zheng J and Wei A: The carcinogenic role of the notch signaling pathway in the development of hepatocellular carcinoma. J Cancer. 10:1570–1579. 2019.PubMed/NCBI View Article : Google Scholar
20	Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehár J, Kryukov GV, Sonkin D, et al: The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 483:603–607. 2012.PubMed/NCBI View Article : Google Scholar
21	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.PubMed/NCBI View Article : Google Scholar
22	Yehya AHS, Asif M, Petersen SH, Subramaniam AV, Kono K, Majid AMSA and Oon CE: Angiogenesis: Managing the culprits behind tumorigenesis and metastasis. Medicina (Kaunas). 54(8)2018.PubMed/NCBI View Article : Google Scholar
23	Zhang YC, Xu Z, Zhang TF and Wang YL: Circulating microRNAs as diagnostic and prognostic tools for hepatocellular carcinoma. World J Gastroenterol. 21:9853–9862. 2015.PubMed/NCBI View Article : Google Scholar
24	Wang ZX, Ren SC, Chang ZS and Ren J: Identification of kinesin family member 2A (KIF2A) as a promising therapeutic target for osteosarcoma. Biomed Res Int. 2020(7102757)2020.PubMed/NCBI View Article : Google Scholar
25	Zhang X, Wang Y, Liu X, Zhao A, Yang Z, Kong F, Sun L, Yu Y and Jiang L: KIF2A promotes the progression via AKT signaling pathway and is upregulated by transcription factor ETV4 in human gastric cancer. Biomed Pharmacother. 125(109840)2020.PubMed/NCBI View Article : Google Scholar
26	Lu L, Liu S, Dong Q and Xin Y: Salidroside suppresses the metastasis of hepatocellular carcinoma cells by inhibiting the activation of the Notch1 signaling pathway. Mol Med Rep. 19:4964–4972. 2019.PubMed/NCBI View Article : Google Scholar
27	Liu Y, Su C, Shan Y, Yang S and Ma G: Targeting Notch1 inhibits invasion and angiogenesis of human breast cancer cells via inhibition nuclear Factor-κB signaling. Am J Transl Res. 8:2681–2692. 2016.PubMed/NCBI