MiR-200b Inhibits Tumor Growth and Chemoresistance Via Targeting P70S6K1 in Lung Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2020 May 22

PMID 32435616

Citations 14

Authors

Hui-Fang Jin

Ju-Feng Wang

Ting-Ting Song

Jun Zhang

Lin Wang

Affiliations

Soon will be listed here.

Abstract

Downregulation of microRNA-200b (miR-200b) has been identified in a range of cancers, yet the specific mechanisms whereby it influences lung cancer growth require further exploration. We determined that lung cancer patient tumor samples exhibit decreased miR-200b expression, and we further found this miRNA to inhibit tumor growth via interfering with ERK1/2 and AKT signaling, targeting p70S6K1 to suppress HIF-1α expression. This miRNA further rendered H1299 cells more sensitive to cisplatin while impairing their proliferative and invasive potential through its ability to target and inhibit the activity of p70S6K1. These results were further confirmed in a murine xenograft model in which miR-200b also inhibited the growth of tumor and suppressed p70S6K1, p-AKT, p-ERK1/2, and HIF-1α expression. These findings clearly demonstrate a role for miR-200b in suppressing lung cancer development, making it a potentially relevant target for future diagnostic and therapeutic interventions.

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References

Ye F, Tang H, Liu Q, Xie X, Wu M, Liu X . miR-200b as a prognostic factor in breast cancer targets multiple members of RAB family. J Transl Med. 2014; 12:17. PMC: 3898994. DOI: 10.1186/1479-5876-12-17. View

Pearce L, Komander D, Alessi D . The nuts and bolts of AGC protein kinases. Nat Rev Mol Cell Biol. 2009; 11(1):9-22. DOI: 10.1038/nrm2822. View

Stewart D . Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer. Crit Rev Oncol Hematol. 2010; 75(3):173-234. PMC: 2888634. DOI: 10.1016/j.critrevonc.2009.11.006. View

Jiao A, Sui M, Zhang L, Sun P, Geng D, Zhang W . MicroRNA-200c inhibits the metastasis of non-small cell lung cancer cells by targeting ZEB2, an epithelial-mesenchymal transition regulator. Mol Med Rep. 2016; 13(4):3349-55. DOI: 10.3892/mmr.2016.4901. View

Du Y, Xu Y, Ding L, Yao H, Yu H, Zhou T . Down-regulation of miR-141 in gastric cancer and its involvement in cell growth. J Gastroenterol. 2009; 44(6):556-61. DOI: 10.1007/s00535-009-0037-7. View

Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90. DOI: 10.3322/caac.20107. View

Pretre V, Wicki A . Inhibition of Akt and other AGC kinases: A target for clinical cancer therapy?. Semin Cancer Biol. 2017; 48:70-77. DOI: 10.1016/j.semcancer.2017.04.011. View

Zhang H, Alshareef A, Wu C, Jiao J, Sorensen P, Lai R . miR-200b induces cell cycle arrest and represses cell growth in esophageal squamous cell carcinoma. Carcinogenesis. 2016; 37(9):858-869. PMC: 5008252. DOI: 10.1093/carcin/bgw079. View

Park S, Gaur A, Lengyel E, Peter M . 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. PMC: 2279201. DOI: 10.1101/gad.1640608. View

10.

Sun Q, Liu T, Yuan Y, Guo Z, Xie G, Du S . MiR-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting UBQLN1. Int J Cancer. 2014; 136(5):1003-12. DOI: 10.1002/ijc.29065. View

11.

Jemal A, Siegel R, Xu J, Ward E . Cancer statistics, 2010. CA Cancer J Clin. 2010; 60(5):277-300. DOI: 10.3322/caac.20073. View

12.

Zhao X, Dou W, He L, Liang S, Tie J, Liu C . MicroRNA-7 functions as an anti-metastatic microRNA in gastric cancer by targeting insulin-like growth factor-1 receptor. Oncogene. 2012; 32(11):1363-72. DOI: 10.1038/onc.2012.156. View

13.

Calin G, Croce C . MicroRNA signatures in human cancers. Nat Rev Cancer. 2006; 6(11):857-66. DOI: 10.1038/nrc1997. View

14.

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2013. CA Cancer J Clin. 2013; 63(1):11-30. DOI: 10.3322/caac.21166. View

15.

Yang W, Bai J, Liu D, Wang S, Zhao N, Che R . MiR-93-5p up-regulation is involved in non-small cell lung cancer cells proliferation and migration and poor prognosis. Gene. 2018; 647:13-20. DOI: 10.1016/j.gene.2018.01.024. View

16.

Li J, Tan Q, Yan M, Liu L, Lin H, Zhao F . miRNA-200c inhibits invasion and metastasis of human non-small cell lung cancer by directly targeting ubiquitin specific peptidase 25. Mol Cancer. 2014; 13:166. PMC: 4105889. DOI: 10.1186/1476-4598-13-166. View

17.

Pasquinelli A . MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet. 2012; 13(4):271-82. DOI: 10.1038/nrg3162. View

18.

Ceppi P, Mudduluru G, Kumarswamy R, Rapa I, Scagliotti G, Papotti M . Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer. Mol Cancer Res. 2010; 8(9):1207-16. DOI: 10.1158/1541-7786.MCR-10-0052. View

19.

Fenton T, Gout I . Functions and regulation of the 70kDa ribosomal S6 kinases. Int J Biochem Cell Biol. 2010; 43(1):47-59. DOI: 10.1016/j.biocel.2010.09.018. View

20.

Kopp F, Wagner E, Roidl A . The proto-oncogene KRAS is targeted by miR-200c. Oncotarget. 2013; 5(1):185-95. PMC: 3960200. DOI: 10.18632/oncotarget.1427. View