Knockdown of KIF3C Inhibits Epithelial-Mesenchymal Transition in Lung Cancer Cells A549
Download PDF

Keywords

KIF3C
A549
EMT
Lung cancer

DOI

10.26689/jcnr.v6i5.4360

Submitted : 2022-08-27
Accepted : 2022-09-11
Published : 2022-09-26

Abstract

The objective of this study is to reveal the role of KIF3C gene in the proliferation of lung cancer cells, and the regulation of epithelial mesenchymal transition (EMT) of tumor cells. The plate clone formation assay and cell scratch assay were used in this study to detect the changes of cell proliferation and migration ability after siKIF3C interference, while EMT-related protein expression after KIF3C downregulation was detected by Western blot. The cell clone formation assay showed that the number of clones of lung cancer cells A549 was significantly reduced after transfected with siKIF3C  (P<0.05); The scratch assay showed that the healing ability of cells was significantly reduced after transfected with siKIF3C (P<0.05); Western blot protein analysis revealed that the levels of EMT-related proteins, N-cadherin, Vimentin, Snail, and Slug were significantly down-regulated (P<0.05), however, E-cadherin protein levels were up-regulated after siKIF3C interference. In conclusion, KIF3C may promote the proliferation and invasive ability of lung cancer cells A549 through EMT.

References

Tan AC, Tan DSW, 2022, Targeted Therapies for Lung Cancer Patients with Oncogenic Driver Molecular Alterations. J Clin Oncol, 40(6): 611–625.

Yang SR, Schultheis AM, Yu H, et al., 2022, Precision Medicine in Non-Small Cell Lung Cancer: Current Applications and Future Directions. Semin Cancer Biol, 2022(84): 184–198.

Kevenaar ST, Bianchi S, Spronsen M, et al., 2016, Kinesinbinding Protein Controls Microtubule Dynamics and Cargo Trafficking by Regulating Kinesin Motor Activity. Current Biology, 26(7): 849–861.

Hirokawa N, Niwa S, Tanaka Y, 2010, Molecular Motors in Neurons: Transport Mechanisms and Roles in Brain Function, Development, and Disease. Neuron, 68(4): 610–638.

Yang Z, Goldstein LS, 1998, Characterization of the KIF3C Neural Kinesin-Like Motor from Mouse. Molecular Biology of the Cell, 9(2): 249–261.

Gumy LF, Chew DJ, Tortosa E, et al., 2013, The Kinesin-2 Family Member KIF3C Regulates Microtubule Dynamics and is Required for Axon Growth and Regeneration. J Neurosci, 33(28): 11329–11345.

Liu H, Liu R, Hao M, et al., 2021, Kinesin Family Member 3C (KIF3C) as a Novel Nonsmall Cell Lung Cancer (NSCLC) Oncogene whose Expression is Modulated by Microrna-150-5p (Mir-150-5p) And Microrna-186-3p (Mir-186-3p). Bioengineered, 12(1): 3077–3088.

Imyanitov EN, Iyevleva AG, Levchenko EN, 2021, Molecular Testing and Targeted Therapy for Non-Small Cell Lung Cancer: Current Status and Perspectives. Crit Rev Oncol Hematol, 2021(157): 103194.

Wang M, Herbst RS, Boshoff C, 2021, Toward Personalized Treatment Approaches For Non-Small-Cell Lung Cancer. Nat Med, 27(8): 1345–1356.

Hirokawa N, Noda Y, 2008, Intracellular Transport and Kinesin Superfamily Proteins, Kifs: Structure, Function, and Dynamics. Physiol Rev, 88(3): 1089–1118.

Wang C, Wang C, Wei Z, et al., 2015, Suppression of Motor Protein KIF3C Expression Inhibits Tumor Growth and Metastasis in Breast Cancer by Inhibiting TGF-? Signaling. Cancer Lett, 368 (1): 105–114.

Lens SMA, Voest EE, Medema RH, 2010, Shared and Separate Functions of Polo-Like Kinases and Aurora Kinases in Cancer. Nat Rev Cancer, 10(12): 825–841.

Rath O, Kozielski F, 2012, Kinesins and cancer. Nat Rev Cancer 12(8): 527–539.

Diefenbach RJ, Mackay JP, Armati PJ, et al., 1998, The C-Terminal Region of the Stalk Domain of Ubiquitous Human Kinesin Heavy Chain Contains the Binding Site for Kinesin Light Chain. Biochemistry, 37(47): 16663–16670.

Lucanus AJ, Yip GW, 2018, Kinesin Superfamily: Roles in Breast Cancer, Patient Prognosis, and Therapeutics. Oncogene, 37(7): 833–838.

De S, Cipriano R, Jackson MW, et al., 2009, Overexpression of Kinesins Mediates Docetaxel Resistance in Breast Cancer Cells. Cancer Res, 69(20): 8035–8042.

Li X, Huang W, Huang W, et al., 2020, Kinesin Family Members KIF2C/4A/10/11/14/18B/ 20A/23 Predict Poor Prognosis and Promote Cell Proliferation in Hepatocellular Carcinoma. Am J Transl Res, 12(5): 1614–1639.

Yao W, Jia X, Xu L, et al., 2021, Microrna-2053 Involves in the Progression of Esophageal Cancer by Targeting KIF3C. Cell Cycle, 2021, 20(12): 1163–1172.

Babaei G, Aziz SG, Jaghi NZZ, 2021, EMT, Cancer Stem Cells, and Autophagy: The Three Main Axes of Metastasis. Biomed Pharmacother, 2021(133): 110909.

Brabletz S, Schuhwerk H, Brabletz T, et al., 2021, Dynamic EMT: A Multi-Tool for Tumor Progression. EMBO J, 40(18): e108647.