The Wnt/β-Catenin/LEF1 Pathway Promotes Cell Proliferation at Least in Part Through Direct Upregulation of MiR-17-92 Cluster

Overview

Journal Front Genet

Date 2019 Jun 14

PMID 31191623

Citations 7

Authors

Fang Mu

Jiaxin Huang

Tianyu Xing

Yang Jing

Tingting Cui

Yaqi Guo

Xiaohong Yan

Hui Li

Ning Wang

Affiliations

Soon will be listed here.

Abstract

The miR-17-92 cluster is involved in animal development and homeostasis, and its dysregulation leads to human diseases such as cancer. In the present study, we investigated the functional link between miR-17-92 cluster and Wnt/β-catenin signaling pathway in ICP2 and DF1 cells. We demonstrated that ectopic expression of either LEF1 or β-catenin increased the promoter activity of the miR-17-92 cluster host gene (MIR17HG) and combined ectopic expression of LEF1 and β-catenin further enhanced the promoter activity; while knockdown of either LEF1 or β-catenin reduced the MIR17HG promoter activity. Both LEF1 and β-catenin could directly bind to the MIR17HG promoter. Furthermore, we demonstrated that low doses of lithium chloride (LiCl), an activator of Wnt/β-catenin signaling pathway, increased MIR17HG promoter activity and the endogenous expression of the miR-17-92 cluster, while high doses of LiCl had the opposite effects. Treatment with XAV-939, an inactivator of the Wnt/β-catenin pathway, reduced the endogenous expression of miR-17-92 cluster. Finally, we found that low doses of LiCl promoted the proliferation of ICP2 and DF1 cells, while high doses of LiCl inhibited the proliferation of ICP2 and DF1 cells. Taken together, our results reveal that MIR17HG is a target of LEF1 and the Wnt/β-catenin pathway and suggest that the miR-17-92 cluster may, at least in part, mediate the proliferation-promoting effect of the Wnt/β-catenin pathway in cell proliferation.

Citing Articles

Insight into dysregulated VEGF-related genes in diabetic retinopathy through bioinformatic analyses.

Wang X, He X, Li Z, Mu T, Pang L, Ma W Naunyn Schmiedebergs Arch Pharmacol. 2024; .

PMID: 39725717 DOI: 10.1007/s00210-024-03638-y.

CFTR represses a PDX1 axis to govern pancreatic ductal cell fate.

Rotti P, Yi Y, Gasser G, Yuan F, Sun X, Apak-Evans I iScience. 2024; 27(12):111393.

PMID: 39687022 PMC: 11647141. DOI: 10.1016/j.isci.2024.111393.

Identification of key transcription factors and their functional role involved in Salmonella typhimurium infection in chicken using integrated transcriptome analysis and bioinformatics approach.

Ahmad S, Bhat S, Shafi S, Dar M, Saleem A, Haq Z BMC Genomics. 2023; 24(1):214.

PMID: 37098463 PMC: 10127038. DOI: 10.1186/s12864-023-09315-3.

Circ_CLIP2 promotes glioma progression through targeting the miR-195-5p/HMGB3 axis.

Xiao B, Lv S, Wu M, Shen X, Tu W, Ye M J Neurooncol. 2021; 154(2):131-144.

PMID: 34357490 DOI: 10.1007/s11060-021-03814-7.

Loss of DEK Expression Induces Alzheimer's Disease Phenotypes in Differentiated SH-SY5Y Cells.

Greene A, Parks L, Solomon M, Privette Vinnedge L Front Mol Neurosci. 2020; 13:594319.

PMID: 33304240 PMC: 7701170. DOI: 10.3389/fnmol.2020.594319.

References

Eastman Q, Grosschedl R . Regulation of LEF-1/TCF transcription factors by Wnt and other signals. Curr Opin Cell Biol. 1999; 11(2):233-40. DOI: 10.1016/s0955-0674(99)80031-3. View

Shtutman M, Zhurinsky J, Simcha I, Albanese C, DAmico M, Pestell R . The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci U S A. 1999; 96(10):5522-7. PMC: 21892. DOI: 10.1073/pnas.96.10.5522. View

Hoeflich K, Luo J, Rubie E, Tsao M, Jin O, Woodgett J . Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature. 2000; 406(6791):86-90. DOI: 10.1038/35017574. View

Bartel D . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. View

Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S . Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res. 2004; 64(9):3087-95. DOI: 10.1158/0008-5472.can-03-3773. View

de Boer J, Wang H, van Blitterswijk C . Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng. 2004; 10(3-4):393-401. DOI: 10.1089/107632704323061753. View

Erdal E, Ozturk N, Cagatay T, Eksioglu-Demiralp E, Ozturk M . Lithium-mediated downregulation of PKB/Akt and cyclin E with growth inhibition in hepatocellular carcinoma cells. Int J Cancer. 2005; 115(6):903-10. DOI: 10.1002/ijc.20972. View

Hughes T, Brady H . Regulation of axin2 expression at the levels of transcription, translation and protein stability in lung and colon cancer. Cancer Lett. 2005; 233(2):338-47. DOI: 10.1016/j.canlet.2005.03.026. View

He L, Thomson J, Hemann M, Hernando-Monge E, Mu D, Goodson S . A microRNA polycistron as a potential human oncogene. Nature. 2005; 435(7043):828-33. PMC: 4599349. DOI: 10.1038/nature03552. View

10.

ODonnell K, Wentzel E, Zeller K, Dang C, Mendell J . c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005; 435(7043):839-43. DOI: 10.1038/nature03677. View

11.

Cao Q, Lu X, Feng Y . Glycogen synthase kinase-3beta positively regulates the proliferation of human ovarian cancer cells. Cell Res. 2006; 16(7):671-7. DOI: 10.1038/sj.cr.7310078. View

12.

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

13.

Sylvestre Y, De Guire V, Querido E, Mukhopadhyay U, Bourdeau V, Major F . An E2F/miR-20a autoregulatory feedback loop. J Biol Chem. 2006; 282(4):2135-43. DOI: 10.1074/jbc.M608939200. View

14.

Rulifson I, Karnik S, Heiser P, Ten Berge D, Chen H, Gu X . Wnt signaling regulates pancreatic beta cell proliferation. Proc Natl Acad Sci U S A. 2007; 104(15):6247-52. PMC: 1847455. DOI: 10.1073/pnas.0701509104. View

15.

Fontana L, Pelosi E, Greco P, Racanicchi S, Testa U, Liuzzi F . MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation. Nat Cell Biol. 2007; 9(7):775-87. DOI: 10.1038/ncb1613. View

16.

Eulalio A, Huntzinger E, Izaurralde E . Getting to the root of miRNA-mediated gene silencing. Cell. 2008; 132(1):9-14. DOI: 10.1016/j.cell.2007.12.024. View

17.

Ventura A, Young A, Winslow M, Lintault L, Meissner A, Erkeland S . Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008; 132(5):875-86. PMC: 2323338. DOI: 10.1016/j.cell.2008.02.019. View

18.

Yu Z, Wang C, Wang M, Li Z, Casimiro M, Liu M . A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol. 2008; 182(3):509-17. PMC: 2500136. DOI: 10.1083/jcb.200801079. View

19.

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

20.

Northcott P, Fernandez-L A, Hagan J, Ellison D, Grajkowska W, Gillespie Y . The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursors. Cancer Res. 2009; 69(8):3249-55. PMC: 2836891. DOI: 10.1158/0008-5472.CAN-08-4710. View