MicroRNA-92a promotes proliferation and invasiveness of gastric cancer cell by targeting FOXO1 gene

Jiawei Yu; Qingfeng Ni; Shu Zhang; Ruheng Hua; Ran Tao; Chong Tang; Shichun Feng

doi:10.14715/cmb/2019.66.1.16

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Vol. 66 No. 1: Issue 1

Issue Published : April 25, 2020

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MicroRNA-92a promotes proliferation and invasiveness of gastric cancer cell by targeting FOXO1 gene

https://doi.org/10.14715/cmb/2019.66.1.16

Jiawei Yu

Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Chongchuan District, Nantong City, Jiangsu Province, 226001, China

Qingfeng Ni

Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Chongchuan District, Nantong City, Jiangsu Province, 226001, China

Shu Zhang

Department of Pathology, Affiliated Hospital of Nantong University, 20 Xisi Road, Chongchuan District, Nantong City, Jiangsu Province, 226001, China

Ruheng Hua

Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Chongchuan District, Nantong City, Jiangsu Province, 226001, China

Ran Tao

Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Chongchuan District, Nantong City, Jiangsu Province, 226001, China

Chong Tang

Department of Gastrointestinal Surgery, Nantong First People's Hospital, No.6, North Haier Lane Road, Nantong City, Jiangsu Province, 226001, China

Shichun Feng

Department of Gastrointestinal Surgery, Nantong First People's Hospital, No.6, North Haier Lane Road, Nantong City, Jiangsu Province, 226001, China

Corresponding Author(s) : Shichun Feng

nhqzh0@163.com

Cellular and Molecular Biology, Vol. 66 No. 1: Issue 1
Article Published : April 20, 2020

Abstract

The aim of this study is to investigate the effect of miRNA-92a on GC cell proliferation, migration and invasiveness, and the mechanism(s) involved. Four GC cell lines (SGC-7901, BGC-823, MKN45 and HGC-27) and normal human gastric epithelial cells (GES1) were used in this study. MicroRNA-92a mimics or inhibitor were transfected into the cells. The results of transfection were assessed using real-time quantitative polymerase chain reaction (qRT-PCR). Cell proliferation, migration, invasiveness and apoptosis were determined using cell counting kit 8 (CCK-8), scratch test, Transwell invasion assay, and flow cytometric analysis, respectively. The protein target of miRNA-92a was predicted using Bioinformatics. The expression of FOXO1 protein was measured using Western blotting. The expression of miRNA-92a was significantly upregulated in GC cells, relative to normal gastric epithelial cells (p < 0.05). Overexpression of miRNA-92a significantly promoted the proliferation, migration and invasiveness of GC cells, but significantly inhibited their apoptosis (p < 0.05). MicroRNA-92a directly targeted FOXO1 gene, and significantly reduced its protein expression. Overexpression of miRNA-92a promotes the proliferation, migration and invasiveness of GC cells, and plays a role similar to that of oncogene. It directly targets FOXO1 gene by inhibiting its protein expression.

Keywords

Gastric cancer MicroRNA-92a Cell proliferation FOXO1 gene Expression.

Yu, J., Ni, Q., Zhang, S., Hua, R., Tao, R., Tang, C., & Feng, S. (2020). MicroRNA-92a promotes proliferation and invasiveness of gastric cancer cell by targeting FOXO1 gene. Cellular and Molecular Biology, 66(1), 95–100. https://doi.org/10.14715/cmb/2019.66.1.16

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References

Fuyuhiro Y, Yashiro M, Noda S, Kashiwagi S, Matsuoka J, Doi Y, et al. Upregulation of cancer-associated myofibroblasts by TGF-Î² from scirrhous gastric carcinoma cells. Br J Cancer 2011; 105: 996.
Kubota E, Williamson CT, Ye R, Elegbede A, Peterson L, Lees-Miller SP, et al. Low ATM protein expression and depletion of p53 correlates with olaparib sensitivity in gastric cancer cell lines. Cell Cycle 2014; 13: 2129-2137.
Cuperus JT, Fahlgren N, Carrington JC. Evolution and functional diversification of MIRNA genes. The Plant Cell 2011; 23: 431-442.
Borkowski R, Du L, Zhao Z, McMillan E, Kosti A, Yang CR, et al. Genetic Mutation of p53 and Suppression of the miR-17 - 92 Cluster Are Synthetic Lethal in Non–Small Cell Lung Cancer due to Upregulation of Vitamin D Signaling. Cancer Res 2015; 75: 666-675.
Ke TW, Wei PL, Yeh KT, Chen WT, Cheng YW. MiR-92a promotes cell metastasis of colorectal cancer through PTEN-mediated PI3K/AKT pathway. Ann Surg Oncol 2015; 22: 2649-2655.
Shigoka M, Tsuchida A, Matsudo T, Nagakawa Y, Saito H, Suzuki Y, et al. Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development. Pathol Int 2010; 60: 351-357.
Baer C, Claus R, Plass C. Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res 2013; 73: 473-477.
Chandra S, Vimal D, Sharma D, Rai V, Gupta SC, Chowdhuri DK. Role of miRNAs in development and disease: Lessons learnt from small organisms. Life Sci 2017; 185: 8-14.
Mogilyansky E, Rigoutsos I. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ 2013; 20: 1603.
Tsuchida A, Ohno S, Wu W, Borjigin N, Fujita K, Aoki T, et al. miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer. Cancer Sci 2011; 102: 2264-2271.
Motawi TK, Rizk SM, Ibrahim TM, Ibrahim IA. Circulating microRNAs, miR-92a, miR-100 and miR-143, as non-invasive biomarkers for bladder cancer diagnosis. Cell Biochem Funct 2016; 34: 142-148.
Liu GH, Zhou ZG, Chen R, Wang MJ, Zhou B, Li Y, et al. Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer. Tumor Biol 2013; 34: 2175-2181.
Chen Z, Zhao X, Wang J, Li BZ, Wang Z, Sun J, et al. MicroRNA-92a promotes lymph node metastasis of human esophageal squamous cell carcinoma via E-cadherin. J Biol Chem 2011; 286: 10725-10734.
Ren C, Wang W, Han C, Chen H, Fu D, Luo Y, et al. Expression and prognostic value of miR-92a in patients with gastric cancer. Tumor Biol 2016; 37: 9483-9491.
Webb AE, Brunet A. FOXO transcription factors: key regulators of cellular quality control. Trends Biochem Sci 2014; 39: 159-169.
van der Vos KE, Coffer PJ. The extending network of FOXO transcriptional target genes. Antioxid Redox Signal 2011; 14: 579-592.
Kim SY, San-Ko Y, Park J, Choi Y, Park JW, Kim Y, et al. Forkhead transcription factor FOXO1 inhibits angiogenesis in gastric cancer in relation to SIRT1. Cancer Res Treat 2016; 48: 345.
Park J, San-Ko Y, Yoon J, Kim MA, Park JW, Kim WH, et al. The forkhead transcription factor FOXO1 mediates cisplatin resistance in gastric cancer cells by activating phosphoinositide 3-kinase/Akt pathway. Gastric Cancer 2014; 17: 423-430.
Kim SY, Yoon J, San-Ko Y, Chang MS, Park JW, Lee HE, et al. Constitutive phosphorylation of the FOXO1 transcription factor in gastric cancer cells correlates with microvessel area and the expressions of angiogenesis-related molecules. BMC Cancer 2011; 11: 264.
Stahl M, Dijkers PF, Kops GJPL, Lens SM, Coffer PJ, Burgering BM, et al. The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J Immunol 2002; 168: 5024-5031.
Procaccia S, Ordan M, Cohen I, Bendetz-Nezer S, Seger R. Direct binding of MEK1 and MEK2 to AKT induces Foxo1 phosphorylation, cellular migration and metastasis. Sci Rep 2017; 7: 43078.

References

Fuyuhiro Y, Yashiro M, Noda S, Kashiwagi S, Matsuoka J, Doi Y, et al. Upregulation of cancer-associated myofibroblasts by TGF-Î² from scirrhous gastric carcinoma cells. Br J Cancer 2011; 105: 996.

Kubota E, Williamson CT, Ye R, Elegbede A, Peterson L, Lees-Miller SP, et al. Low ATM protein expression and depletion of p53 correlates with olaparib sensitivity in gastric cancer cell lines. Cell Cycle 2014; 13: 2129-2137.

Cuperus JT, Fahlgren N, Carrington JC. Evolution and functional diversification of MIRNA genes. The Plant Cell 2011; 23: 431-442.

Borkowski R, Du L, Zhao Z, McMillan E, Kosti A, Yang CR, et al. Genetic Mutation of p53 and Suppression of the miR-17 - 92 Cluster Are Synthetic Lethal in Non–Small Cell Lung Cancer due to Upregulation of Vitamin D Signaling. Cancer Res 2015; 75: 666-675.

Ke TW, Wei PL, Yeh KT, Chen WT, Cheng YW. MiR-92a promotes cell metastasis of colorectal cancer through PTEN-mediated PI3K/AKT pathway. Ann Surg Oncol 2015; 22: 2649-2655.

Shigoka M, Tsuchida A, Matsudo T, Nagakawa Y, Saito H, Suzuki Y, et al. Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development. Pathol Int 2010; 60: 351-357.

Baer C, Claus R, Plass C. Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res 2013; 73: 473-477.

Chandra S, Vimal D, Sharma D, Rai V, Gupta SC, Chowdhuri DK. Role of miRNAs in development and disease: Lessons learnt from small organisms. Life Sci 2017; 185: 8-14.

Mogilyansky E, Rigoutsos I. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ 2013; 20: 1603.

Tsuchida A, Ohno S, Wu W, Borjigin N, Fujita K, Aoki T, et al. miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer. Cancer Sci 2011; 102: 2264-2271.

Motawi TK, Rizk SM, Ibrahim TM, Ibrahim IA. Circulating microRNAs, miR-92a, miR-100 and miR-143, as non-invasive biomarkers for bladder cancer diagnosis. Cell Biochem Funct 2016; 34: 142-148.

Liu GH, Zhou ZG, Chen R, Wang MJ, Zhou B, Li Y, et al. Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer. Tumor Biol 2013; 34: 2175-2181.

Chen Z, Zhao X, Wang J, Li BZ, Wang Z, Sun J, et al. MicroRNA-92a promotes lymph node metastasis of human esophageal squamous cell carcinoma via E-cadherin. J Biol Chem 2011; 286: 10725-10734.

Ren C, Wang W, Han C, Chen H, Fu D, Luo Y, et al. Expression and prognostic value of miR-92a in patients with gastric cancer. Tumor Biol 2016; 37: 9483-9491.

Webb AE, Brunet A. FOXO transcription factors: key regulators of cellular quality control. Trends Biochem Sci 2014; 39: 159-169.

van der Vos KE, Coffer PJ. The extending network of FOXO transcriptional target genes. Antioxid Redox Signal 2011; 14: 579-592.

Kim SY, San-Ko Y, Park J, Choi Y, Park JW, Kim Y, et al. Forkhead transcription factor FOXO1 inhibits angiogenesis in gastric cancer in relation to SIRT1. Cancer Res Treat 2016; 48: 345.

Park J, San-Ko Y, Yoon J, Kim MA, Park JW, Kim WH, et al. The forkhead transcription factor FOXO1 mediates cisplatin resistance in gastric cancer cells by activating phosphoinositide 3-kinase/Akt pathway. Gastric Cancer 2014; 17: 423-430.

Kim SY, Yoon J, San-Ko Y, Chang MS, Park JW, Lee HE, et al. Constitutive phosphorylation of the FOXO1 transcription factor in gastric cancer cells correlates with microvessel area and the expressions of angiogenesis-related molecules. BMC Cancer 2011; 11: 264.

Stahl M, Dijkers PF, Kops GJPL, Lens SM, Coffer PJ, Burgering BM, et al. The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J Immunol 2002; 168: 5024-5031.

Procaccia S, Ordan M, Cohen I, Bendetz-Nezer S, Seger R. Direct binding of MEK1 and MEK2 to AKT induces Foxo1 phosphorylation, cellular migration and metastasis. Sci Rep 2017; 7: 43078.

Author biographies is not available.