Invaze karcinomu prostaty je podporována nedostatkem NDRG1 vyvolaným miR-96-5p prostřednictvím regulace NF-κB

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Authors: A. A. Soror ¹; R. Eshagh ¹; M. R. Fahim ¹; A. Jamshidian ^2,3; G. H. Monfared ^1,3
Authors‘ workplace: Department of Biology, Faculty of Biological Sciences, East Tehran Branch (Ghiamdasht), Islamic Azad University, Tehran, Iran ¹; Tehran Medical Genetics Laboratory, Tehran, Iran ²; Molecular Genetic and Reproductive Biology Department, Kowsar Poly-clinic, Tehran, Iran ³
Published in: Klin Onkol 2024; 38(2): 95-101
Category: Reviews
doi: https://doi.org/10.48095/ccko202495

Overview

Východiska: N-myc downstream-regulovaný gen 1 (NDRG1) má významnou funkci při progresi nádorů. U karcinomu prostaty (prostate cancer – PCa) však regulační mechanizmus NDRG1 zůstává nejasný. Materiál a metody: Hladiny exprese miR-96-5p a NDRG1 byly hodnoceny v buněčných liniích PCa a v tkáních prostaty a validovány ve veřejných databázích pomocí polymerázové řetězové reakce v reálném čase, analýzy western blot a imunohistochemie. Funkce miR-96-5p a NDRG1 byla zkoumána pomocí testů hojení ran a transwell testů in vitro a testu myšího xenoimplantátu in vivo. Dráha regulovaná pomocí NDRG1 byla testována technikou sekvenování nové generace. K detekci vztahu mezi miR-96-5p, NDRG1 a NF-kB dráhou byl použit imunofluorescenční test a test s luciferázou. Výsledky: Nadměrná exprese NDRG1 potlačuje migraci, invazi a epiteliálně-mezenchymální přechod (EMT) in vitro a inhibuje metastázy in vivo. Navíc miR-96-5p přispívá k deficitu NDRG1 a podporuje migraci a invazi buněk PCa. Kromě toho ztráta NDRG1 aktivuje dráhu NF-kB, která stimuluje fosforylaci p65 a IKBa a indukuje EMT v PCa. Závěr: MiR-96-5p podporuje migraci a invazi PCa tím, že cílí na NDRG1 a reguluje dráhu NF-kB.

Klíčová slova:

karcinom prostaty – NDRG1 – miR-96-5p – NF-kB – EMT

Sources

1. Sung H, Ferlay J, Siegel RL et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71 (3): 209–249. doi: 10.3322/caac.21660.

2. Zhang K, Bangma CH, Roobol MJ. Prostate cancer screening in Europe and Asia. Asian J Urol 2017; 4 (2): 86–95. doi: 10.1016/j.ajur.2016.08.010.

3. Fang BA, Kovacevic Z, Park KC et al. Molecular functions of the iron-regulated metastasis suppressor, NDRG1, and its potential as a molecular target for cancer therapy. Biochim Biophys Acta 2014; 1845 (1): 1–19. doi: 10.1016/ j.bbcan.2013.11.002.

4. Qu X, Zhai Y, Wei H et al. Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family. Mol Cell Biochem 2002; 229 (1–2): 35–44. doi: 10.1023/a: 1017934810825.

5. Nieto MA, Huang RY, Jackson RA et al. EMT: 2016. Cell 2016; 166 (1): 21–45. doi: 10.1016/j.cell.2016.06.028.

6. Thiery JP, Acloque H, Huang RYJ et al. Epithelial-mesenchymal transitions in development and disease. Cell 1999; 139 (5): 871–890. doi: 10.1016/j.cell.2009.11.007.

7. Liu W, Yue F, Zheng M et al. The proto-oncogene c-Src and its downstream signaling pathways are inhibited by the metastasis suppressor, NDRG1. Oncotarget 2015; 6 (11): 8851–8874. doi: 10.18632/oncotarget.3316.

8. Wangpu X, Lu J, Xi R et al. Targeting the metastasis suppressor, N-myc downstream regulated gene-1, with novel di-2-pyridylketone thiosemicarbazones: suppression of tumor cell migration and cell-collagen adhesion by inhibiting focal adhesion kinase/paxillin signaling. Mol Pharmacol 2016; 89 (5): 521–540. doi: 10.1124/mol.115.103044.

9. Jin R, Liu W, Menezes S et al. The metastasis suppressor NDRG1 modulates the phosphorylation and nuclear translocation of beta-catenin through mechanisms involving FRAT1 and PAK4. J Cell Sci 2014; 127 (14): 3116–3130. doi: 10.1242/jcs.147835.

10. Tu LC, Yan X, Hood L et al. Proteomics analysis of the interactome of N-myc downstream-regulated gene 1 and its interactions with the androgen response program in prostate cancer cells. Mol Cell Proteomics 2007; 6 (4): 575–588. doi: 10.1074/mcp.M600249-MCP200.

11. Xi R, Pun IH, Menezes SV et al. Novel thiosemicarbazones inhibit lysine-rich carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) coisolated (LYRIC) and the LYRIC-induced epithelial-mesenchymal transition via upregulation of N-myc downstream-regulated gene 1 (NDRG1). Mol Pharmacol 2017; 91 (5): 499–517. doi: 10.1124/mol.116.107870.

12. Lee JC, Chung LC, YJ Chen et al. N-myc downstream-regulated gene 1 downregulates cell proliferation, invasiveness, and tumorigenesis in human oral squamous cell carcinoma. Cancer Lett 2014; 355 (2): 242–252. doi: 10.1016/j.canlet.2014.08.035.

13. Hu ZY, Xie WB, Yang F et al. NDRG1 attenuates epithelial-mesenchymal transition of nasopharyngeal cancer cells via blocking Smad2 signaling. Biochim Biophys Acta 2015; 1852 (9): 1876–1886. doi: 10.1016/j.bbadis.2015.06.009.

14. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136 (2): 215–233. doi: 10.1016/j.cell.2009.01.002.

15. Li J, Ye D, Shen P et al. Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway. J Exp Clin Cancer Res 2020; 39 (1): 212. doi: 10.1186/s13046-020-01718-4.

16. Ren D, Yang Q, Dai Y et al. Oncogenic miR-210-3p promotes prostate cancer cell EMT and bone metastasis via NF-kappaB signaling pathway. Mol Cancer 2017; 16 (1): 117. doi: 10.1186/s12943-017-0688-6.

17. Anderson O, Guttilla Reed IK. Regulation of cell growth and migration by miR-96 and miR-183 in a breast cancer model of epithelial-mesenchymal transition. PLoS One 2020; 15 (5): e0233187. doi: 10.1371/journal.pone.0233187.

18. Huang X, Lv W, Zhang JH et al. MiR96 functions as a tumor suppressor gene by targeting NUAK1 in pancreatic cancer. Int J Mol Med 2014; 34 (6): 1599–1605. doi: 10.3892/ijmm.2014.1940.

19. Liu ZM, Wu ZY, Li WH et al. MiR-96-5p promotes the proliferation, invasion, and metastasis f papillary thyroid carcinoma through down-regulating CCDC67. Eur Rev Med Pharmacol Sci 2019; 23 (8): 3421–3430. doi: 10.26355/eurrev_201904_17706.

20. Ress AL, Stiegelbauer V, Winter E et al. MiR-96-5p influences cellular growth and is associated with poor survival in colorectal cancer patients. Mol Carcinog 2015; 54 (11): 1442–1450. doi: 10.1002/mc.22218.

21. Yao Q, Pei Y, Zhang X et al. MicroRNA-96 acts as a tumor suppressor gene in human osteosarcoma via target regulation of EZRIN. Life Sci 2018; 203: 1–11. doi: 10.1016/j.lfs.2018.04.012.

22. He C, Zhang Q, Gu R et al. MiR-96 regulates migration and invasion of bladder cancer through epithelial-mesenchymal transition in response to transforming growth factor-beta1. J Cell Biochem 2018; 119 (9): 7807–7817. doi: 10.1002/jcb.27172.

23. Wang H, Ma N, Li W et al. MicroRNA-96-5p promotes proliferation, invasion and EMT of oral carcinoma cells by directly targeting FOXF2. Biol Open 2020; 9 (3): bio049478. doi: 10.1242/bio.049478.

24. Wei S, Zheng Y, Jiang Y et al. The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p. EBioMedicine 2019; 44: 182–193. doi: 10.1016/j.ebiom.2019.05.032.

25. Pudova EA, Krasnov GS, Nyushko KM et al. MiRNAs expression signature potentially associated with lymphatic dissemination in locally advanced prostate cancer. BMC Med Genomics 2020; 13 (Suppl 8): 129. doi: 10.1186/s12920-020-00788-e9.

26. Siu MK, Tsai YC, Chang YS et al. Transforming growth factor-beta promotes prostate bone metastasis through induction of microRNA-96 and activation of the mTOR pathway. Oncogene 2015; 34 (36): 4767–4776. doi: 10.1038/onc.2014.414.

27. Tsai YC, Chen WY, Siu MK et al. Epidermal growth factor receptor signaling promotes metastatic prostate cancer through microRNA-96-mediated downregulation of the tumor suppressor ETV6. Cancer Lett 2017; 384: 1–8. doi: 10.1016/j.canlet.2016.10.014.

28. Voss G, Haflidadottir BS, Jaremo H et al. Regulation of cell-cell adhesion in prostate cancer cells by microRNA-96 through upregulation of E-Cadherin and EpCAM. Carcinogenesis 2020; 41 (7): 865–874. doi: 10.1093/carcin/bgz191.

29. Miettinen PJ, Ebner R, Lopez AR et al. TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. J Cell Biol 1994; 127 (6 Pt 2): 2021–2036. doi: 10.1083/jcb.127.6.2021.

30. Wang M, Ren D, Guo W et al. N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell--like traits via ErbB signaling in prostate cancer cells. Int J Oncol 2016; 48 (2): 595–606. doi: 10.3892/ijo.2015.3270.

31. Hoesel B, Schmid JA. The complexity of NF-kappaB signaling in inflammation and cancer. Mol Cancer 2013; 12: 86. doi: 10.1186/1476-4598-12-86.

32. Liu W, Wang S, Sun Q et al. DCLK1 promotes epithelial-mesenchymal transition via the PI3K/Akt/NF-kappaB pathway in colorectal cancer. Int J Cancer 2018; 142 (10): 2068–2079. doi: 10.1002/ijc.31232.

33. Mei LL, Wang WJ, Qiu YT et al. MiR-145-5p suppresses tumor cell migration, invasion, and epithelial to mesenchymal transition by regulating the Sp1/NF-kappaB signaling pathway in esophageal squamous cell carcinoma. Int J Mol Sci 2017; 18 (9): 1833. doi: 10.3390/ijms180 91833.

34. Wang J, Tian L, Khan MN et al. Ginsenoside Rg3 sensitize hypoxic lung cancer cells to cisplatin via the blocking of NF-kappaB mediated epithelial-mesenchymal transition and stemness. Cancer Lett 2018; 415: 73–85. doi: 10.1016/j.canlet.2017.11.037.

35. Zhang J, Kuang Y, Wang Y et al. Notch-4 silencing inhibits prostate cancer growth and EMT via the NF-kappaB pathway. Apoptosis 2017; 22 (6): 877–884. doi: 10.1007/s10495-017-1368-0.

36. Li Y, Pan P, Qiao P et al. Downregulation of N-myc downstream-regulated gene1 caused by the methylation of CpG islands of NDRG1 promoter promotes proliferation and invasion of prostate cancer cells. Int J Oncol 2015; 47 (3): 1001–1008. doi: 10.3892/ijo.2015. 3086.

37. Oncomine Solution for Next-Generation Sequencing. [online]. Available from: https: //www.oncomine.com/

38. Find more NCBI PubMed artoicles. [online]. Available from: https: //www.genomenon.com/mastermind-lp-gads-ncbi-search/?gad_source=1&gclid=Cj0KCQjwq86wBhDiARIsAJhuphnPBfH4VPcdKhN3WeYSBB_e3Qv0QTZVqyzyBROks11l4SHktBX9ZqAaAicbEALw_wcB.

39. NIH National Cancer Institute. [online]. Available from: https: //www.cancer.gov/

40. Liu R, Li J, Teng Z et al. Overexpressed microRNA-182 promotes proliferation and invasion in prostate cancer PC-3 cells by down-regulating N-myc downstream-regulated gene 1 (NDRG1). PLoS One 2013; 8 (7): e68982. doi: 10.1371/journal.pone.0068982.

41. http: //www.targetscan.org.

42. Bandyopadhyay S, Pai SK, Hirota S et al. Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression. Oncogene 2004; 23 (33): 5675–5681. doi: 10.1038/sj.onc.1207734.

43. Matsugaki T, Zenmyo M, Hiraoka K et al. N-myc downstream-regulated gene 1/Cap43 expression promotes cell differentiation of human osteosarcoma cells. Oncol Rep 2010; 24 (3): 721–725. doi: 10.3892/or_00000913.

44. Mi L, Zhu F, Yang X et al. The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells. Oncogene 2017; 36 (30): 4323–4335. doi: 10.1038/onc.2017.74.