Fibrillin 2 gene knockdown inhibits invasion and migration of lung cancer  cells

Qiaojun Hong; Rong Li; Yiyan Zhang; Kangsheng Gu

doi:10.14715/cmb/2020.66.7.29

Issue

Vol. 66 No. 7: Issue 7

Issue Published : November 9, 2020

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

Fibrillin 2 gene knockdown inhibits invasion and migration of lung cancer cells

https://doi.org/10.14715/cmb/2020.66.7.29

Qiaojun Hong

Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

Rong Li

Department of Oncology, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Department of Oncology, Taikang Xianlin Drum Tower Hospital Clinical College of Wuhan University, China

Yiyan Zhang

Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

Kangsheng Gu

Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

Corresponding Author(s) : Kangsheng Gu

zubp56@163.com

Cellular and Molecular Biology, Vol. 66 No. 7: Issue 7
Article Published : October 31, 2020

Abstract

To investigate the effect of Fibrillin 2 (FBN2) expression on the invasion and migration of lung cancer cells, and the underlying mechanism. Protein and mRNA expressions of FBN2 were assayed. The relationship between FBN2 protein expression and clinical characteristics of lung cancer patients was analyzed. Correlation between FBN2 expression level and patient survival time was analyzed. Moreover, the mRNA and protein expression of FBN2 in lung cancer cells and human normal lung epithelial cells were assayed. After constructing low-expressing FBN2 cells, the cell proliferation, clone formation, migration and invasion capabilities were tested. Lung cancer cells proliferation with low FBN2 expression in nude mice was measured with a nude mouse tumorigenic experiment. The mRNA and protein expressions of FBN2 in lung cancer tissues were significantly higher than those in para-cancerous tissues (p<0.05). FBN2 protein expression was significantly correlated with TNM stage, lymph node metastasis and histological type (p<0.05). Survival time was markedly reduced in patients with high FBN2 expression (p<0.001). The expressions of FBN2 mRNA and protein were markedly higher in lung cancer cells than in human normal lung epithelial cells. The proliferation, migration and invasion of lung cancer cells were significantly inhibited by FBN2 knockdown. The FBN2 knockdown significantly inhibited the protein expressions of p-FAK, p-MEK and p-ERK. FBN2 is highly expressed in lung cancer tissues, and as an oncogene, it affects the pathogenesis of lung cancer. The knockdown of the expression of FBN2 significantly inhibits the proliferation, invasion and migration abilities of lung cancer cells.

Keywords

Fibrillin 2 FBN2 Fibrillin 2 gene knockdown Lung cancer cells.

Hong, Q., Li, R., Zhang, Y., & Gu, K. (2020). Fibrillin 2 gene knockdown inhibits invasion and migration of lung cancer cells. Cellular and Molecular Biology, 66(7), 190–196. https://doi.org/10.14715/cmb/2020.66.7.29

Download Citation

References

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 60: 10-29.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statisticsin China, 2015. CA Cancer J Clin 2016; 66: 115-132.
Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res 2018; 30: 1-12.
Kulis M, Esteller M. DNA methylation and cancer. Adv Genet 2010; 70: 27.
Levenson VV. DNA methylation biomarkers of cancer: Moving toward clinical application. Pharmacogenomics 2016; 5: 699-707.
Wittenberger T, Sleigh S, Reisel D, Zikan M, Wahl B, Alunni-Fabbroni M, et al. DNA methylation makers for early detection of women's cancer: Promise and challenges. Epigenomics 2017; 6: 311.
Bakulski KM, Dolinoy DC, Sartor MA, Paulson HL, Konen JR, Lieberman AP, et al. Genome-wide DNA methylation difference between late-onset Alzheimr's disease and cognitively normal controls in human frontal cortex. J Alzheimers Dis 2017; 29: 571-588.
Yang Q, Ota K, Tian Y, Kumar A, Wada J, Kashihara N, et al. Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung. Dev Biol 1999; 212: 229-242.
Hagihara A, Miyamoto K, Furuta J, Hiraoka N, Wakazono K, Seki S, et al. Identification of 27 5' Cp G islands aberrantly methylated and 13 genes silenced in human pancreatic cancers. Oncogene 2004; 23: 8705-8710.
Cortese R, Hartmann O, Berlin K, Eckhardt F. Correlative gene expression and DNA methylation profiling in lung development nominate new biomarkers in lung cancer. Int J Biochem Cell Biol 2008; 40: 1494-1508.
Gou W, Zhou X, Liu Z, Wang L, Shen J, Xu X, et al. CD74-ROS1 G2032R mutation transcriptionally up-regulates Twist1 in non-small cell lung cancer cells leading to increased migration, invasion, and resistance to crizotinib. Cancer Lett 2018; 422: 19-28.
Li Y, Gao A, Yu L. Monitoring of TGF-beta 1-Induced Human Lung Adenocarcinoma A549 Cells Epithelial-Mesenchymal Transformation Process by Measuring Cell Adhesion Force with a Microfluidic Device. Appl Biochem Biotechnol 2016; 178: 114-125.
Geng F, Jiang Z, Song X, Zhou H, Zhao H. Mdig suppresses epithelial-mesenchymal transition and inhibits the invasion and metastasis of non-small cell lung cancer via regulating GSK-3ï¢/ï¢-catenin signaling. Int J Oncol 2017; 51: 1898-1908.
Chen JS, Li HS, Huang JQ, Dong SH, Huang ZJ, Yi W, et al. MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma. Cancer Lett 2016; 375: 73-83.
Peidl A, Perbal B, Leask A. Yin/Yang expression of CCN family members: Transforming growth factor beta 1, via ALK5/FAK/MEK, induces CCN1 and CCN2, yet suppresses CCN3, expression in human dermal fibroblasts. PLoS One 2019; 14: 218178.
Qi ZH, Xu HX, Zhang SR, Xu JZ, Li S, Gao HL, et al. RIPK4/PEBP1 axis promotes pancreatic cancer cell migration and invasion by activating RAF1/MEK/ERK signaling. Int J Oncol 2018; 52: 1105-1116.

References

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 60: 10-29.

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statisticsin China, 2015. CA Cancer J Clin 2016; 66: 115-132.

Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res 2018; 30: 1-12.

Kulis M, Esteller M. DNA methylation and cancer. Adv Genet 2010; 70: 27.

Levenson VV. DNA methylation biomarkers of cancer: Moving toward clinical application. Pharmacogenomics 2016; 5: 699-707.

Wittenberger T, Sleigh S, Reisel D, Zikan M, Wahl B, Alunni-Fabbroni M, et al. DNA methylation makers for early detection of women's cancer: Promise and challenges. Epigenomics 2017; 6: 311.

Bakulski KM, Dolinoy DC, Sartor MA, Paulson HL, Konen JR, Lieberman AP, et al. Genome-wide DNA methylation difference between late-onset Alzheimr's disease and cognitively normal controls in human frontal cortex. J Alzheimers Dis 2017; 29: 571-588.

Yang Q, Ota K, Tian Y, Kumar A, Wada J, Kashihara N, et al. Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung. Dev Biol 1999; 212: 229-242.

Hagihara A, Miyamoto K, Furuta J, Hiraoka N, Wakazono K, Seki S, et al. Identification of 27 5' Cp G islands aberrantly methylated and 13 genes silenced in human pancreatic cancers. Oncogene 2004; 23: 8705-8710.

Cortese R, Hartmann O, Berlin K, Eckhardt F. Correlative gene expression and DNA methylation profiling in lung development nominate new biomarkers in lung cancer. Int J Biochem Cell Biol 2008; 40: 1494-1508.

Gou W, Zhou X, Liu Z, Wang L, Shen J, Xu X, et al. CD74-ROS1 G2032R mutation transcriptionally up-regulates Twist1 in non-small cell lung cancer cells leading to increased migration, invasion, and resistance to crizotinib. Cancer Lett 2018; 422: 19-28.

Li Y, Gao A, Yu L. Monitoring of TGF-beta 1-Induced Human Lung Adenocarcinoma A549 Cells Epithelial-Mesenchymal Transformation Process by Measuring Cell Adhesion Force with a Microfluidic Device. Appl Biochem Biotechnol 2016; 178: 114-125.

Geng F, Jiang Z, Song X, Zhou H, Zhao H. Mdig suppresses epithelial-mesenchymal transition and inhibits the invasion and metastasis of non-small cell lung cancer via regulating GSK-3ï¢/ï¢-catenin signaling. Int J Oncol 2017; 51: 1898-1908.

Chen JS, Li HS, Huang JQ, Dong SH, Huang ZJ, Yi W, et al. MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma. Cancer Lett 2016; 375: 73-83.

Peidl A, Perbal B, Leask A. Yin/Yang expression of CCN family members: Transforming growth factor beta 1, via ALK5/FAK/MEK, induces CCN1 and CCN2, yet suppresses CCN3, expression in human dermal fibroblasts. PLoS One 2019; 14: 218178.

Qi ZH, Xu HX, Zhang SR, Xu JZ, Li S, Gao HL, et al. RIPK4/PEBP1 axis promotes pancreatic cancer cell migration and invasion by activating RAF1/MEK/ERK signaling. Int J Oncol 2018; 52: 1105-1116.

Author biographies is not available.