MicroRNA-10b Regulates Epithelial-mesenchymal Transition by Modulating KLF4/Notch1/E-cadherin in Cisplatin-resistant Nasopharyngeal Carcinoma Cells

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2016 May 18

PMID 27186392

Citations 31

Authors

Pei Zhang

Haiyu Hong

Xiaojin Sun

Hao Jiang

Shiyin Ma

Surong Zhao

Mengxiao Zhang

Zhiwei Wang

Chenchen Jiang

Hao Liu

Affiliations

Soon will be listed here.

Abstract

Epithelial-mesenchymal transition (EMT) is an initiating event in tumor cell invasion and metastasis that contributes to therapeutic resistance to compounds including cisplatin. MicroRNAs (miRNAs) have been associated with EMT as well as resistance to standard therapies. However, the underlying mechanisms by which miRNAs control the development of resistance to cisplatin (DDP), and the accompanying EMT-like properties are required to elucidate. Here we show that microRNA-10b (miR-10b) is up-regulated in HNE1/DDP cells, and inhibition of miR-10b expression reversed the EMT phenotype. However, over-expression of miR-10b was able to promote the acquisition of an EMT phenotype in HNE1 cells. Additionally, we identified that miR-10b expression inversely correlates with KLF4, which then controls expression of Notch1. Knock-down of Notch1 inhibited cell migration, invasion, and reversed EMT in HNE1/DDP cells, which was dependent on miR-10b. In summary, our results reveal that miR-10b regulates EMT by modulating KLF4/Notch1/E-cadherin expression, which promotes invasion and migration of nasal pharyngeal carcinoma cells.

Citing Articles

Inhibition of miR-10b treats metastatic breast cancer by targeting stem cell-like properties.

Halim A, Al-Qadi N, Kenyon E, Conner K, Mondal S, Medarova Z Oncotarget. 2024; 15:591-606.

PMID: 39189967 PMC: 11348941. DOI: 10.18632/oncotarget.28641.

Chromosomal structural rearrangements implicate long non-coding RNAs in rare germline disorders.

Andersen R, Alkuraya I, Ajeesh A, Sakamoto T, Mena E, Amr S Hum Genet. 2024; 143(7):921-938.

PMID: 39060644 PMC: 11294402. DOI: 10.1007/s00439-024-02693-y.

HOTTIP Mediated Therapy Resistance in Glioma Cells Involves Regulation of EMT-Related miR-10b.

Li Z, Li M, Xia P, Lu Z Front Oncol. 2022; 12:873561.

PMID: 35402278 PMC: 8987496. DOI: 10.3389/fonc.2022.873561.

Low miR-10b-3p associated with sorafenib resistance in hepatocellular carcinoma.

Shao Y, Chen P, Lin L, Lee B, Ling A, Cheng A Br J Cancer. 2022; 126(12):1806-1814.

PMID: 35236936 PMC: 9174288. DOI: 10.1038/s41416-022-01759-w.

The role of non-coding RNAs in chemotherapy for gastrointestinal cancers.

Dashti F, Mirazimi S, Rabiei N, Fathazam R, Rabiei N, Piroozmand H Mol Ther Nucleic Acids. 2021; 26:892-926.

PMID: 34760336 PMC: 8551789. DOI: 10.1016/j.omtn.2021.10.004.

References

Sun L, Yan W, Wang Y, Sun G, Luo H, Zhang J . MicroRNA-10b induces glioma cell invasion by modulating MMP-14 and uPAR expression via HOXD10. Brain Res. 2011; 1389:9-18. DOI: 10.1016/j.brainres.2011.03.013. View

Tiwari N, Meyer-Schaller N, Arnold P, Antoniadis H, Pachkov M, van Nimwegen E . Klf4 is a transcriptional regulator of genes critical for EMT, including Jnk1 (Mapk8). PLoS One. 2013; 8(2):e57329. PMC: 3581489. DOI: 10.1371/journal.pone.0057329. View

Kong D, Li Y, Wang Z, Banerjee S, Ahmad A, Kim H . miR-200 regulates PDGF-D-mediated epithelial-mesenchymal transition, adhesion, and invasion of prostate cancer cells. Stem Cells. 2009; 27(8):1712-21. PMC: 3400149. DOI: 10.1002/stem.101. View

Gasque Schoof C, Botelho E, Izzotti A, Dos Reis Vasques L . MicroRNAs in cancer treatment and prognosis. Am J Cancer Res. 2012; 2(4):414-33. PMC: 3410578. View

Mao L, Zhang Y, Deng X, Mo W, Yu Y, Lu H . Transcription factor KLF4 regulates microRNA-544 that targets YWHAZ in cervical cancer. Am J Cancer Res. 2015; 5(6):1939-53. PMC: 4529615. View

Banerjee S, Banerjee S . CCN5/WISP-2: A micromanager of breast cancer progression. J Cell Commun Signal. 2012; 6(2):63-71. PMC: 3368018. DOI: 10.1007/s12079-012-0158-2. View

Sun Y, Shen S, Liu X, Tang H, Wang Z, Yu Z . MiR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinoma. Mol Cell Biochem. 2014; 390(1-2):19-30. PMC: 3972435. DOI: 10.1007/s11010-013-1950-x. View

Zhang G, Zhu H, Wang Y, Yang S, Liu M, Zhang W . Krüppel-like factor 4 represses transcription of the survivin gene in esophageal cancer cell lines. Biol Chem. 2009; 390(5-6):463-9. DOI: 10.1515/BC.2009.060. View

Iorio M, Croce C . Causes and consequences of microRNA dysregulation. Cancer J. 2012; 18(3):215-22. PMC: 3528102. DOI: 10.1097/PPO.0b013e318250c001. View

10.

Lee J, Park M, Park J, Lee H, Shin D, Kang Y . Loss of the polycomb protein Mel-18 enhances the epithelial-mesenchymal transition by ZEB1 and ZEB2 expression through the downregulation of miR-205 in breast cancer. Oncogene. 2013; 33(10):1325-35. DOI: 10.1038/onc.2013.53. View

11.

Chen Q, Wen Y, Guo L, Liu H, Huang P, Mo H . Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst. 2011; 103(23):1761-70. DOI: 10.1093/jnci/djr432. View

12.

Xie M, Zhang L, He C, Xu F, Liu J, Hu Z . Activation of Notch-1 enhances epithelial-mesenchymal transition in gefitinib-acquired resistant lung cancer cells. J Cell Biochem. 2011; 113(5):1501-13. DOI: 10.1002/jcb.24019. View

13.

Ambros V . MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell. 2003; 113(6):673-6. DOI: 10.1016/s0092-8674(03)00428-8. View

14.

Latifi A, Luwor R, Bilandzic M, Nazaretian S, Stenvers K, Pyman J . Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: molecular phenotype of chemoresistant ovarian tumors. PLoS One. 2012; 7(10):e46858. PMC: 3466197. DOI: 10.1371/journal.pone.0046858. View

15.

Lin J, Teo S, Lam D, Jeyaseelan K, Wang S . MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme. Cell Death Dis. 2012; 3:e398. PMC: 3481123. DOI: 10.1038/cddis.2012.134. View

16.

Li Y, Ma J, Qian X, Wu Q, Xia J, Miele L . Regulation of EMT by Notch signaling pathway in tumor progression. Curr Cancer Drug Targets. 2013; 13(9):957-62. DOI: 10.2174/15680096113136660101. View

17.

Liu Z, Teng L, Bailey S, Frost A, Bland K, LoBuglio A . Epithelial transformation by KLF4 requires Notch1 but not canonical Notch1 signaling. Cancer Biol Ther. 2009; 8(19):1840-51. PMC: 2795010. DOI: 10.4161/cbt.8.19.9440. View

18.

Xiao H, Li H, Yu G, Xiao W, Hu J, Tang K . MicroRNA-10b promotes migration and invasion through KLF4 and HOXD10 in human bladder cancer. Oncol Rep. 2014; 31(4):1832-8. DOI: 10.3892/or.2014.3048. View

19.

Dong C, Wu W, Feng S, Wang X, Shao J, Qiao J . Co-inhibition of microRNA-10b and microRNA-21 exerts synergistic inhibition on the proliferation and invasion of human glioma cells. Int J Oncol. 2012; 41(3):1005-12. DOI: 10.3892/ijo.2012.1542. View

20.

Luo A, Kong J, Hu G, Liew C, Xiong M, Wang X . Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene. 2003; 23(6):1291-9. DOI: 10.1038/sj.onc.1207218. View