COUP‑TFII promotes epithelial‑mesenchymal transition by inhibiting miR‑34a expression in colorectal cancer

Bao,Ying; Lu,Yongliang; Feng,Wenming; Yu,Hongbin; Guo,Huihui; Tao,Yulong; Shi,Qian; Chen,Wei; Wang,Xiang

doi:10.3892/ijo.2019.4718

COUP‑TFII promotes epithelial‑mesenchymal transition by inhibiting miR‑34a expression in colorectal cancer

Authors:
- Ying Bao
- Yongliang Lu
- Wenming Feng
- Hongbin Yu
- Huihui Guo
- Yulong Tao
- Qian Shi
- Wei Chen
- Xiang Wang
View Affiliations

Affiliations: First Affiliated Hospital, Huzhou University, The First People's Hospital of Huzhou, Huzhou, Zhejiang 313000, P.R. China, Department of Medicine, Huzhou University, Huzhou, Zhejiang 313000, P.R. China, Cancer Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang 310012, P.R. China
Published online on: February 18, 2019 https://doi.org/10.3892/ijo.2019.4718
Pages: 1337-1344

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chicken ovalbumin upstream promoter‑transcription factor II (COUP‑TFII) expression is upregulated in colorectal cancer and is associated with its progression and a poor prognosis. The aim of the present study was to determine whether COUP‑TFII regulates colorectal cancer cell (CRC) invasion and migration by inhibiting microRNA (miR)‑34a. Transwell system and wound healing assays were performed to examine cell invasiveness and migration, respectively. Reverse transcription polymerase chain reaction and western blotting were used to detect the RNA and protein levels of target molecules, respectively. The results revealed that COUP‑TFII knockdown significantly inhibited CRC invasion and migration. In addition, the expression of miR‑34a, a well‑known tumor suppressor was revealed to be inversely correlated with COUP‑TFII expression. The miR‑34a mimic significantly reduced CRC invasion and migration abilities, while the miR‑34a inhibitor enhanced CRC invasion and migration activity. There was no significant difference between the negative small interfering RNA and miR‑34a inhibitor groups following knockdown of COUP‑TFII. Furthermore, western blotting demonstrated that miR‑34a mimics inhibited the epithelial‑mesenchymal transition (EMT) process of CRCs, while the miR‑34a inhibitor had the opposite effect. Taken together, the results demonstrate that miR‑34a regulates CRC invasion and migration by examining the mechanism by which COUP‑TFII regulates EMT.

View Figures

View References

1	Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014. View Article : Google Scholar : PubMed/NCBI
2	Ait Ouakrim D, Pizot C, Boniol M, Malvezzi M, Boniol M, Negri E, Bota M, Jenkins MA, Bleiberg H and Autier P: Trends in colorectal cancer mortality in Europe: Retrospective analysis of the WHO mortality database. BMJ. 351:h49702015. View Article : Google Scholar : PubMed/NCBI
3	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
4	Wang LH, Tsai SY, Cook RG, Beattie WG, Tsai MJ and O'Malley BW: COUP transcription factor is a member of the steroid receptor superfamily. Nature. 340:163–166. 1989. View Article : Google Scholar : PubMed/NCBI
5	Tran P, Zhang XK, Salbert G, Hermann T, Lehmann JM and Pfahl M: COUP orphan receptors are negative regulators of retinoic acid response pathways. Mol Cell Biol. 12:4666–4676. 1992. View Article : Google Scholar : PubMed/NCBI
6	Cooney AJ, Tsai SY, O'Malley BW and Tsai MJ: Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors. Mol Cell Biol. 12:4153–4163. 1992. View Article : Google Scholar : PubMed/NCBI
7	Kliewer SA, Umesono K, Heyman RA, Mangelsdorf DJ, Dyck JA and Evans RM: Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. Proc Natl Acad Sci USA. 89:1448–1452. 1992. View Article : Google Scholar : PubMed/NCBI
8	Bailey P, Sartorelli V, Hamamori Y and Muscat GE: The orphan nuclear receptor, COUP-TF II, inhibits myogenesis by post-transcriptional regulation of MyoD function: COUP-TF II directly interacts with p300 and myoD. Nucleic Acids Res. 26:5501–5510. 1998. View Article : Google Scholar : PubMed/NCBI
9	Pereira FA, Tsai MJ and Tsai SY: COUP-TF orphan nuclear receptors in development and differentiation. Cell Mol Life Sci. 57:1388–1398. 2000. View Article : Google Scholar : PubMed/NCBI
10	Heery R, Finn SP, Cuffe S and Gray SG: Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells. Cancers (Basel). 9:92017. View Article : Google Scholar
11	Xu M, Qin J, Tsai SY and Tsai MJ: The role of the orphan nuclear receptor COUP-TFII in tumorigenesis. Acta Pharmacol Sin. 36:32–36. 2015. View Article : Google Scholar :
12	Feng Q, Wu X, Li F, Ning B, Lu X, Zhang Y, Pan Y and Guan W: miR-27b inhibits gastric cancer metastasis by targeting NR2F2. Protein Cell. 8:114–122. 2017. View Article : Google Scholar :
13	Qin J, Chen X, Xie X, Tsai MJ and Tsai SY: COUP-TFII regulates tumor growth and metastasis by modulating tumor angiogenesis. Proc Natl Acad Sci USA. 107:3687–3692. 2010. View Article : Google Scholar : PubMed/NCBI
14	Qin J, Chen X, Yu-Lee LY, Tsai MJ and Tsai SY: Nuclear receptor COUP-TFII controls pancreatic islet tumor angio-genesis by regulating vascular endothelial growth factor/vascular endothelial growth factor receptor-2 signaling. Cancer Res. 70:8812–8821. 2010. View Article : Google Scholar : PubMed/NCBI
15	Zheng J, Qin W, Jiao D, Ren J, Wei M, Shi S, Xi W, Wang H, Yang AG, Huan Y, et al: Knockdown of COUP-TFII inhibits cell proliferation and induces apoptosis through upregulating BRCA1 in renal cell carcinoma cells. Int J Cancer. 139:1574–1585. 2016. View Article : Google Scholar : PubMed/NCBI
16	Pereira FA, Qiu Y, Tsai MJ and Tsai SY: Chicken ovalbumin upstream promoter transcription factor (COUP-TF): Expression during mouse embryogenesis. J Steroid Biochem Mol Biol. 53:503–508. 1995. View Article : Google Scholar : PubMed/NCBI
17	Bao Y, Gu D, Feng W, Sun X, Wang X, Zhang X, Shi Q, Cui G, Yu H, Tang C, et al: COUP-TFII regulates metastasis of colorectal adenocarcinoma cells by modulating Snail1. Br J Cancer. 111:933–943. 2014. View Article : Google Scholar : PubMed/NCBI
18	Zhang W, Liu J, Qiu J, Fu X, Tang Q, Yang F, Zhao Z and Wang H: MicroRNA-382 inhibits prostate cancer cell proliferation and metastasis through targeting COUP-TFII. Oncol Rep. 36:3707–3715. 2016. View Article : Google Scholar : PubMed/NCBI
19	Zhang C, Han Y, Huang H, Qu L and Shou C: High NR2F2 transcript level is associated with increased survival and its expression inhibits TGF-β-dependent epithelial-mesenchymal transition in breast cancer. Breast Cancer Res Treat. 147:265–281. 2014. View Article : Google Scholar : PubMed/NCBI
20	Eulalio A, Huntzinger E and Izaurralde E: Getting to the root of miRNA-mediated gene silencing. Cell. 132:9–14. 2008. View Article : Google Scholar : PubMed/NCBI
21	Deng B, Wang B, Fang J, Zhu X, Cao Z, Lin Q, Zhou L and Sun X: MiRNA-203 suppresses cell proliferation, migration and invasion in colorectal cancer via targeting of EIF5A2. Sci Rep. 6:283012016. View Article : Google Scholar : PubMed/NCBI
22	Wang JX, Zhang QJ, Pei SG and Yang BL: Effect and mechanism of miR-34a on proliferation, apoptosis and invasion of laryngeal carcinoma cells. Asian Pac J Trop Med. 9:494–498. 2016. View Article : Google Scholar : PubMed/NCBI
23	Xue F, Liu Y, Zhang H, Wen Y, Yan L, Tang Q, Xiao E and Zhang D: Let-7a enhances the sensitivity of hepatocellular carcinoma cells to cetuximab by regulating STAT3 expression. OncoTargets Ther. 9:7253–7261. 2016. View Article : Google Scholar
24	Dong X, Jin Z, Chen Y, Xu H, Ma C, Hong X, Li Y and Zhao G: Knockdown of long non-coding RNA ANRIL inhibits proliferation, migration, and invasion but promotes apoptosis of human glioma cells by upregulation of miR-34a. J Cell Biochem. 119:2708–2718. 2018. View Article : Google Scholar
25	Zhang D, Zhou J and Dong M: Dysregulation of microRNA-34a expression in colorectal cancer inhibits the phosphorylation of FAK via VEGF. Dig Dis Sci. 59:958–967. 2014. View Article : Google Scholar
26	Nguyen DX, Bos PD and Massagué J: Metastasis: From dissemination to organ-specific colonization. Nat Rev Cancer. 9:274–284. 2009. View Article : Google Scholar : PubMed/NCBI
27	Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff SJ, Ciciliano JC, Wells MN, Shah AM, et al: Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 339:580–584. 2013. View Article : Google Scholar : PubMed/NCBI
28	Peng Z, Wang CX, Fang EH, Wang GB and Tong Q: Role of epithelial-mesenchymal transition in gastric cancer initiation and progression. World J Gastroenterol. 20:5403–5410. 2014. View Article : Google Scholar : PubMed/NCBI
29	Hsu CY, Hsieh TH, Tsai CF, Chen HS, Liang PI, Hsu YL and Tsai EM: Synthetic Steroid Hormones Regulated Cell Proliferation Through MicroRNA-34a-5p in Human Ovarian Endometrioma. Biol Reprod. 94:602016. View Article : Google Scholar : PubMed/NCBI
30	Beg MS, Brenner AJ, Sachdev J, Borad M, Kang YK, Stoudemire J, Smith S, Bader AG, Kim S and Hong DS: Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Invest New Drugs. 35:180–188. 2017. View Article : Google Scholar
31	Imani S, Wei C, Cheng J, Khan MA, Fu S, Yang L, Tania M, Zhang X, Xiao X, Zhang X, et al: MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion. Oncotarget. 8:21362–21379. 2017. View Article : Google Scholar : PubMed/NCBI
32	Zhou B, Song J, Han T, Huang M, Jiang H, Qiao H, Shi J and Wang Y: MiR-382 inhibits cell growth and invasion by targeting NR2F2 in colorectal cancer. Mol Carcinog. 55:2260–2267. 2016. View Article : Google Scholar : PubMed/NCBI
33	Toiyama Y, Yasuda H, Saigusa S, Tanaka K, Inoue Y, Goel A and Kusunoki M: Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer. Carcinogenesis. 34:2548–2557. 2013. View Article : Google Scholar : PubMed/NCBI
34	Wang C, Zhou Y, Ruan R, Zheng M, Han W and Liao L: High expression of COUP-TF II cooperated with negative Smad4 expression predicts poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol. 8:7112–7121. 2015.PubMed/NCBI
35	Bringuier PP, Schalken JA, Hervieu V and Giroldi LA: Involvement of orphan nuclear receptor COUP-TFII in cadherin-6 and cadherin-11 regulation: Implications in development and cancer. Mech Dev. 136:64–72. 2015. View Article : Google Scholar : PubMed/NCBI