MicroRNA-424/E2F6 Feedback Loop Modulates Cell Invasion, Migration and EMT in Endometrial Carcinoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Jan 27

PMID 29371986

Citations 18

Authors

Zheng Lu

Zhou Nian

Zhang Jingjing

Luo Tao

Li Quan

Affiliations

Soon will be listed here.

Abstract

Our previous study explored the roles of microRNA-424 (miR-424) in the development of endometrial carcinoma (EC) and analyzed the miR-424/E2F7 axis in EC cell growth. In this study, we investigated the status of miR-424 in human endometrial cancer tissues, which were collected from a cohort of Zunyi patients. We found that the expression level of miR-424 was associated with clinical tumor stage, cell differentiation, lymph node metastasis and cell migration ability. Cell function experiments demonstrated that miR-424 overexpression suppressed the invasion and migration abilities of endometrial carcinoma cells . Bioinformatic predictions and dual-luciferase reporter assays suggested E2F6 as a possible target of miR-424. RT-PCR and western blot assays demonstrated that miR-424 transfection reduced the expression level of E2F6, while inhibiting miR-424 with ASO-miR-424 (antisense oligonucleotides of miR-424) increased the expression level of E2F6. Cell function experiments indicated that E2F6 transfection rescued the EC cell phenotype induced by miR-424. In addition, we also found that E2F6 negatively regulated miR-424 expression in EC cells. In summary, our results demonstrated that the miR-424/E2F6 feedback loop modulates cell invasion, migration and EMT in EC and that the miR-424/E2Fs regulation network may serve as a new and potentially important therapeutic target in EC.

Citing Articles

Role of miR-424 in the carcinogenesis.

Ghafouri-Fard S, Askari A, Hussen B, Taheri M, Dilmaghani N Clin Transl Oncol. 2023; 26(1):16-38.

PMID: 37178445 PMC: 10761534. DOI: 10.1007/s12094-023-03209-2.

lncRNA XIST/miR‑129‑2‑3p axis targets CCP110 to regulate the proliferation, invasion and migration of endometrial cancer cells.

Chen S, Liang Y, Shen Y, Wang X Exp Ther Med. 2023; 25(4):159.

PMID: 36911384 PMC: 9996364. DOI: 10.3892/etm.2023.11858.

Deregulated E2F Activity as a Cancer-Cell Specific Therapeutic Tool.

Nakajima R, Zhao L, Zhou Y, Shirasawa M, Uchida A, Murakawa H Genes (Basel). 2023; 14(2).

PMID: 36833320 PMC: 9956157. DOI: 10.3390/genes14020393.

Emerging Role of E2F Family in Cancer Stem Cells.

Xie D, Pei Q, Li J, Wan X, Ye T Front Oncol. 2021; 11:723137.

PMID: 34476219 PMC: 8406691. DOI: 10.3389/fonc.2021.723137.

The Role of miRNAs in the Regulation of Endometrial Cancer Invasiveness and Metastasis-A Systematic Review.

Klicka K, Grzywa T, Klinke A, Mielniczuk A, Wlodarski P Cancers (Basel). 2021; 13(14).

PMID: 34298609 PMC: 8304659. DOI: 10.3390/cancers13143393.

References

Janda M, Gebski V, Davies L, Forder P, Brand A, Hogg R . Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women With Stage I Endometrial Cancer: A Randomized Clinical Trial. JAMA. 2017; 317(12):1224-1233. DOI: 10.1001/jama.2017.2068. View

Zhang M, Gao C, Yang Y, Li G, Dong J, Ai Y . MiR-424 Promotes Non-Small Cell Lung Cancer Progression and Metastasis through Regulating the Tumor Suppressor Gene TNFAIP1. Cell Physiol Biochem. 2017; 42(1):211-221. DOI: 10.1159/000477314. View

Thanapprapasr D, Thanapprapasr K . Molecular therapy as a future strategy in endometrial cancer. Asian Pac J Cancer Prev. 2013; 14(6):3419-23. DOI: 10.7314/apjcp.2013.14.6.3419. View

Bell D . Novel genetic targets in endometrial cancer. Expert Opin Ther Targets. 2014; 18(7):725-30. PMC: 4128487. DOI: 10.1517/14728222.2014.909414. View

Li Q, Qiu X, Li Q, Wang X, Li L, Xu M . MicroRNA-424 may function as a tumor suppressor in endometrial carcinoma cells by targeting E2F7. Oncol Rep. 2015; 33(5):2354-60. DOI: 10.3892/or.2015.3812. View

Tang Y, Zhu L, Li Y, Yu J, Wang J, Zeng X . Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis. Biomed Res Int. 2017; 2017:5905384. PMC: 5376924. DOI: 10.1155/2017/5905384. View

Tang H, Liu P, Yang L, Xie X, Ye F, Wu M . miR-185 suppresses tumor proliferation by directly targeting E2F6 and DNMT1 and indirectly upregulating BRCA1 in triple-negative breast cancer. Mol Cancer Ther. 2014; 13(12):3185-97. DOI: 10.1158/1535-7163.MCT-14-0243. View

Zheng H . The molecular mechanisms of chemoresistance in cancers. Oncotarget. 2017; 8(35):59950-59964. PMC: 5601792. DOI: 10.18632/oncotarget.19048. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

10.

Banno K, Yanokura M, Kisu I, Yamagami W, Susumu N, Aoki D . MicroRNAs in endometrial cancer. Int J Clin Oncol. 2013; 18(2):186-92. DOI: 10.1007/s10147-013-0526-9. View

11.

Shang C, Lu Y, Meng L . MicroRNA-125b down-regulation mediates endometrial cancer invasion by targeting ERBB2. Med Sci Monit. 2012; 18(4):BR149-55. PMC: 3560825. DOI: 10.12659/msm.882617. View

12.

Xu J, Li Y, Wang F, Wang X, Cheng B, Ye F . Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer. Oncogene. 2012; 32(8):976-87. DOI: 10.1038/onc.2012.121. View

13.

Wei S, Li Q, Li Z, Wang L, Zhang L, Xu Z . Correction: miR-424-5p promotes proliferation of gastric cancer by targeting Smad3 through TGF-β signaling pathway. Oncotarget. 2017; 8(20):34018. PMC: 5464930. DOI: 10.18632/oncotarget.17876. View

14.

Bhatnagar N, Li X, Padi S, Zhang Q, Tang M, Guo B . Downregulation of miR-205 and miR-31 confers resistance to chemotherapy-induced apoptosis in prostate cancer cells. Cell Death Dis. 2011; 1:e105. PMC: 3004480. DOI: 10.1038/cddis.2010.85. View

15.

Blenkiron C, Miska E . miRNAs in cancer: approaches, aetiology, diagnostics and therapy. Hum Mol Genet. 2007; 16 Spec No 1:R106-13. DOI: 10.1093/hmg/ddm056. View

16.

Lee J, Park Y, Choi J, Lee Y, Kim C, Choi C . The expression of the miRNA-200 family in endometrial endometrioid carcinoma. Gynecol Oncol. 2010; 120(1):56-62. DOI: 10.1016/j.ygyno.2010.09.022. View

17.

Boren T, Xiong Y, Hakam A, Wenham R, Apte S, Wei Z . MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis. Gynecol Oncol. 2008; 110(2):206-15. DOI: 10.1016/j.ygyno.2008.03.023. View

18.

Li L, Xu Q, Dong Y, Li G, Yang L, Wang L . MiR-181a upregulation is associated with epithelial-to-mesenchymal transition (EMT) and multidrug resistance (MDR) of ovarian cancer cells. Eur Rev Med Pharmacol Sci. 2016; 20(10):2004-10. View

19.

Wu C, Lin W, Chang Y, Lin P, Chen W, Chen M . DNMT1-dependent suppression of microRNA424 regulates tumor progression in human bladder cancer. Oncotarget. 2015; 6(27):24119-31. PMC: 4695174. DOI: 10.18632/oncotarget.4431. View

20.

Ratner E, Tuck D, Richter C, Nallur S, Patel R, Schultz V . MicroRNA signatures differentiate uterine cancer tumor subtypes. Gynecol Oncol. 2010; 118(3):251-7. PMC: 2918705. DOI: 10.1016/j.ygyno.2010.05.010. View