Skip to main content
Top
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Kidney Cancer | Primary research

Up-regulation of microRNA-200c-3p inhibits invasion and migration of renal cell carcinoma cells via the SOX2-dependent Wnt/β-catenin signaling pathway

Authors: Shuai Li, Ziyu Feng, Xuechong Zhang, Dongyang Lan, Yudong Wu

Published in: Cancer Cell International | Issue 1/2019

Login to get access

Abstract

Background

MicroRNA-200c-3p (miR-200c-3p) has been revealed to be related to renal cell carcinoma (RCC) progression, while the inner mechanisms remain unknown. In our study, we intend to unearth the capability of miR-200c-3p in RCC development via the Wnt/β-catenin signaling pathway through binding to SOX2.

Methods

miR-200c-3p, SOX2, β-catenin and GSK3β expression in both tissues and cells of RCC were detected by RT-qPCR or western blot analysis. miR-200c-3p was restored or silenced to determine their biological functions of RCC cells. Expression of SOX2 and related proteins in the Wnt/β-catenin signaling pathway were evaluated by RT-qPCR and western blot analysis. The effect of the combination of downregulated miR-200c-3p and downregulated SOX2 on cell biological behavior change was also determined.

Results

Initially, we found that miR-200c-3p was declined while SOX2, β-catenin and GSK3β was elevated in RCC tissues and cells. A498 cells with the largest difference in miR-200c-3p expression and OS-RC-2 cells with the smallest difference were selected for subsequent experiments. Additionally, upregulated miR-200c-3p and downregulated SOX2 was determined to suppress proliferation, migration, invasion and induce apoptosis of RCC cells. Furthermore, miR-200c-3p inhibited SOX2 to inactivate the Wnt/β-catenin signaling pathway.

Conclusion

Collectively, this study highlights that upregulated miR-200c-3p inhibits expression of SOX2, thereby inhibiting development of RCC cells via modulating the Wnt/β-catenin signaling pathway activation.
Literature
1.
go back to reference Wang X, et al. microRNA-200c modulates the epithelial-to-mesenchymal transition in human renal cell carcinoma metastasis. Oncol Rep. 2013;30(2):643–50.CrossRef Wang X, et al. microRNA-200c modulates the epithelial-to-mesenchymal transition in human renal cell carcinoma metastasis. Oncol Rep. 2013;30(2):643–50.CrossRef
2.
go back to reference Macleod LC, et al. Risk factors for renal cell carcinoma in the VITAL study. J Urol. 2013;190(5):1657–61.CrossRef Macleod LC, et al. Risk factors for renal cell carcinoma in the VITAL study. J Urol. 2013;190(5):1657–61.CrossRef
3.
go back to reference Wang X, et al. miR-200c targets CDK2 and suppresses tumorigenesis in renal cell carcinoma. Mol Cancer Res. 2015;13(12):1567–77.CrossRef Wang X, et al. miR-200c targets CDK2 and suppresses tumorigenesis in renal cell carcinoma. Mol Cancer Res. 2015;13(12):1567–77.CrossRef
4.
go back to reference Yoshino H, et al. Epithelial-mesenchymal transition-related microRNA-200 s regulate molecular targets and pathways in renal cell carcinoma. J Hum Genet. 2013;58(8):508–16.CrossRef Yoshino H, et al. Epithelial-mesenchymal transition-related microRNA-200 s regulate molecular targets and pathways in renal cell carcinoma. J Hum Genet. 2013;58(8):508–16.CrossRef
5.
go back to reference Park SM, et al. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22(7):894–907.CrossRef Park SM, et al. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22(7):894–907.CrossRef
6.
go back to reference Nakada C, et al. Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c. J Pathol. 2008;216(4):418–27.CrossRef Nakada C, et al. Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c. J Pathol. 2008;216(4):418–27.CrossRef
7.
go back to reference White NM, et al. miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol. 2011;186(3):1077–83.CrossRef White NM, et al. miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol. 2011;186(3):1077–83.CrossRef
8.
go back to reference Liu H, et al. Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma. BMC Syst Biol. 2010;4:51.CrossRef Liu H, et al. Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma. BMC Syst Biol. 2010;4:51.CrossRef
9.
go back to reference Chang I, et al. Loss of miR-200c up-regulates CYP1B1 and confers docetaxel resistance in renal cell carcinoma. Oncotarget. 2015;6(10):7774–87.PubMedPubMedCentral Chang I, et al. Loss of miR-200c up-regulates CYP1B1 and confers docetaxel resistance in renal cell carcinoma. Oncotarget. 2015;6(10):7774–87.PubMedPubMedCentral
10.
go back to reference Weina K, Utikal J. SOX2 and cancer: current research and its implications in the clinic. Clin Transl Med. 2014;3:19.CrossRef Weina K, Utikal J. SOX2 and cancer: current research and its implications in the clinic. Clin Transl Med. 2014;3:19.CrossRef
11.
go back to reference Taranova OV, et al. SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes Dev. 2006;20(9):1187–202.CrossRef Taranova OV, et al. SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes Dev. 2006;20(9):1187–202.CrossRef
12.
go back to reference Sarkar A, Hochedlinger K. The sox family of transcription factors: versatile regulators of stem and progenitor cell fate. Cell Stem Cell. 2013;12(1):15–30.CrossRef Sarkar A, Hochedlinger K. The sox family of transcription factors: versatile regulators of stem and progenitor cell fate. Cell Stem Cell. 2013;12(1):15–30.CrossRef
13.
go back to reference Adameyko I, et al. Sox2 and Mitf cross-regulatory interactions consolidate progenitor and melanocyte lineages in the cranial neural crest. Development. 2012;139(2):397–410.CrossRef Adameyko I, et al. Sox2 and Mitf cross-regulatory interactions consolidate progenitor and melanocyte lineages in the cranial neural crest. Development. 2012;139(2):397–410.CrossRef
14.
go back to reference Neumann J, et al. SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer. BMC Cancer. 2011;11:518.CrossRef Neumann J, et al. SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer. BMC Cancer. 2011;11:518.CrossRef
15.
go back to reference Yang F, et al. Elevated expression of SOX2 and FGFR1 in correlation with poor prognosis in patients with small cell lung cancer. Int J Clin Exp Pathol. 2013;6(12):2846–54.PubMedPubMedCentral Yang F, et al. Elevated expression of SOX2 and FGFR1 in correlation with poor prognosis in patients with small cell lung cancer. Int J Clin Exp Pathol. 2013;6(12):2846–54.PubMedPubMedCentral
16.
go back to reference Forghanifard MM, et al. Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma. Med Oncol. 2014;31(4):922.CrossRef Forghanifard MM, et al. Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma. Med Oncol. 2014;31(4):922.CrossRef
17.
go back to reference Wang S, et al. SOX2, a predictor of survival in gastric cancer, inhibits cell proliferation and metastasis by regulating PTEN. Cancer Lett. 2015;358(2):210–9.CrossRef Wang S, et al. SOX2, a predictor of survival in gastric cancer, inhibits cell proliferation and metastasis by regulating PTEN. Cancer Lett. 2015;358(2):210–9.CrossRef
18.
go back to reference Gu W, et al. SOX2 and SOX12 are predictive of prognosis in patients with clear cell renal cell carcinoma. Oncol Lett. 2018;15(4):4564–70.PubMedPubMedCentral Gu W, et al. SOX2 and SOX12 are predictive of prognosis in patients with clear cell renal cell carcinoma. Oncol Lett. 2018;15(4):4564–70.PubMedPubMedCentral
19.
go back to reference Liu Y, et al. Comprehensive analysis of clinical significance of stem-cell related factors in renal cell cancer. World J Surg Oncol. 2011;9:121.CrossRef Liu Y, et al. Comprehensive analysis of clinical significance of stem-cell related factors in renal cell cancer. World J Surg Oncol. 2011;9:121.CrossRef
20.
go back to reference Katoh M. Expression and regulation of WNT1 in human cancer: up-regulation of WNT1 by beta-estradiol in MCF-7 cells. Int J Oncol. 2003;22(1):209–12.PubMed Katoh M. Expression and regulation of WNT1 in human cancer: up-regulation of WNT1 by beta-estradiol in MCF-7 cells. Int J Oncol. 2003;22(1):209–12.PubMed
21.
go back to reference Wen JL, et al. UBE3C promotes growth and metastasis of renal cell carcinoma via activating Wnt/beta-catenin pathway. PLoS ONE. 2015;10(2):e0115622.CrossRef Wen JL, et al. UBE3C promotes growth and metastasis of renal cell carcinoma via activating Wnt/beta-catenin pathway. PLoS ONE. 2015;10(2):e0115622.CrossRef
22.
go back to reference Tutar Y. miRNA and cancer; computational and experimental approaches. Curr Pharm Biotechnol. 2014;15(5):429.CrossRef Tutar Y. miRNA and cancer; computational and experimental approaches. Curr Pharm Biotechnol. 2014;15(5):429.CrossRef
23.
go back to reference Majid S, et al. MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer. Cancer Res. 2011;71(7):2611–21.CrossRef Majid S, et al. MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer. Cancer Res. 2011;71(7):2611–21.CrossRef
24.
go back to reference Yi Z, et al. Differential expression of miRNA patterns in renal cell carcinoma and nontumorous tissues. J Cancer Res Clin Oncol. 2010;136(6):855–62.CrossRef Yi Z, et al. Differential expression of miRNA patterns in renal cell carcinoma and nontumorous tissues. J Cancer Res Clin Oncol. 2010;136(6):855–62.CrossRef
25.
go back to reference Gregory PA, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601.CrossRef Gregory PA, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601.CrossRef
26.
go back to reference Kim T, et al. p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med. 2011;208(5):875–83.CrossRef Kim T, et al. p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med. 2011;208(5):875–83.CrossRef
27.
go back to reference Lengerke C, et al. Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma. BMC Cancer. 2011;11:42.CrossRef Lengerke C, et al. Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma. BMC Cancer. 2011;11:42.CrossRef
28.
go back to reference Stolzenburg S, et al. Targeted silencing of the oncogenic transcription factor SOX2 in breast cancer. Nucleic Acids Res. 2012;40(14):6725–40.CrossRef Stolzenburg S, et al. Targeted silencing of the oncogenic transcription factor SOX2 in breast cancer. Nucleic Acids Res. 2012;40(14):6725–40.CrossRef
29.
go back to reference Ji J, Zheng PS. Expression of Sox2 in human cervical carcinogenesis. Hum Pathol. 2010;41(10):1438–47.CrossRef Ji J, Zheng PS. Expression of Sox2 in human cervical carcinogenesis. Hum Pathol. 2010;41(10):1438–47.CrossRef
30.
go back to reference Su J, et al. MicroRNA-200a suppresses the Wnt/beta-catenin signaling pathway by interacting with beta-catenin. Int J Oncol. 2012;40(4):1162–70.PubMed Su J, et al. MicroRNA-200a suppresses the Wnt/beta-catenin signaling pathway by interacting with beta-catenin. Int J Oncol. 2012;40(4):1162–70.PubMed
31.
go back to reference Chen S, et al. miR-195-5p is critical in REGgamma-mediated regulation of wnt/beta-catenin pathway in renal cell carcinoma. Oncotarget. 2017;8(38):63986–4000.PubMedPubMedCentral Chen S, et al. miR-195-5p is critical in REGgamma-mediated regulation of wnt/beta-catenin pathway in renal cell carcinoma. Oncotarget. 2017;8(38):63986–4000.PubMedPubMedCentral
32.
go back to reference Heavner WE, Andoniadou CL, Pevny LH. Establishment of the neurogenic boundary of the mouse retina requires cooperation of SOX2 and WNT signaling. Neural Dev. 2014;9:27.CrossRef Heavner WE, Andoniadou CL, Pevny LH. Establishment of the neurogenic boundary of the mouse retina requires cooperation of SOX2 and WNT signaling. Neural Dev. 2014;9:27.CrossRef
33.
go back to reference Yang N, et al. Overexpression of SOX2 promotes migration, invasion, and epithelial-mesenchymal transition through the Wnt/beta-catenin pathway in laryngeal cancer Hep-2 cells. Tumour Biol. 2014;35(8):7965–73.CrossRef Yang N, et al. Overexpression of SOX2 promotes migration, invasion, and epithelial-mesenchymal transition through the Wnt/beta-catenin pathway in laryngeal cancer Hep-2 cells. Tumour Biol. 2014;35(8):7965–73.CrossRef
34.
go back to reference Li X, et al. SOX2 promotes tumor metastasis by stimulating epithelial-to-mesenchymal transition via regulation of WNT/beta-catenin signal network. Cancer Lett. 2013;336(2):379–89.CrossRef Li X, et al. SOX2 promotes tumor metastasis by stimulating epithelial-to-mesenchymal transition via regulation of WNT/beta-catenin signal network. Cancer Lett. 2013;336(2):379–89.CrossRef
35.
go back to reference He J, et al. Sox2 inhibits Wnt-beta-catenin signaling and metastatic potency of cisplatin-resistant lung adenocarcinoma cells. Mol Med Rep. 2017;15(4):1693–701.CrossRef He J, et al. Sox2 inhibits Wnt-beta-catenin signaling and metastatic potency of cisplatin-resistant lung adenocarcinoma cells. Mol Med Rep. 2017;15(4):1693–701.CrossRef
36.
go back to reference Thu KL, et al. SOX15 is a candidate tumor suppressor in pancreatic cancer with a potential role in Wnt/beta-catenin signaling. Oncogene. 2014;33(3):279–88.CrossRef Thu KL, et al. SOX15 is a candidate tumor suppressor in pancreatic cancer with a potential role in Wnt/beta-catenin signaling. Oncogene. 2014;33(3):279–88.CrossRef
37.
go back to reference Chen J, et al. Downregulation of miR200c3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2. Oncol Rep. 2018;40(6):3821–9.PubMed Chen J, et al. Downregulation of miR200c3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2. Oncol Rep. 2018;40(6):3821–9.PubMed
38.
go back to reference Peng C, et al. A unilateral negative feedback loop between miR-200 microRNAs and Sox2/E2F3 controls neural progenitor cell-cycle exit and differentiation. J Neurosci. 2012;32(38):13292–308.CrossRef Peng C, et al. A unilateral negative feedback loop between miR-200 microRNAs and Sox2/E2F3 controls neural progenitor cell-cycle exit and differentiation. J Neurosci. 2012;32(38):13292–308.CrossRef
40.
go back to reference Liao X, et al. Matched miRNA and mRNA signatures from an hESC-based in vitro model of pancreatic differentiation reveal novel regulatory interactions. J Cell Sci. 2013;126(Pt 17):3848–61.CrossRef Liao X, et al. Matched miRNA and mRNA signatures from an hESC-based in vitro model of pancreatic differentiation reveal novel regulatory interactions. J Cell Sci. 2013;126(Pt 17):3848–61.CrossRef
41.
go back to reference Banerjee P, Dutta S, Pal R. Dysregulation of Wnt-signaling and a candidate set of miRNAs Underlie the effect of metformin on neural crest cell development. Stem Cells. 2016;34(2):334–45.CrossRef Banerjee P, Dutta S, Pal R. Dysregulation of Wnt-signaling and a candidate set of miRNAs Underlie the effect of metformin on neural crest cell development. Stem Cells. 2016;34(2):334–45.CrossRef
Metadata
Title
Up-regulation of microRNA-200c-3p inhibits invasion and migration of renal cell carcinoma cells via the SOX2-dependent Wnt/β-catenin signaling pathway
Authors
Shuai Li
Ziyu Feng
Xuechong Zhang
Dongyang Lan
Yudong Wu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0944-5

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine