DOI QR코드

DOI QR Code

miR-124 Inhibits Growth and Invasion of Gastric Cancer by Targeting ROCK1

  • Hu, Cong-Bing (Department of General Surgery, The First Affiliated Hospital, Yangtze University) ;
  • Li, Qiao-Lin (Department of General Surgery, The First Affiliated Hospital, Yangtze University) ;
  • Hu, Jian-Fei (Department of General Surgery, The First Affiliated Hospital, Yangtze University) ;
  • Zhang, Qiang (Department of General Surgery, The First Affiliated Hospital, Yangtze University) ;
  • Xie, Jian-Ping (Department of General Surgery, The First Affiliated Hospital, Yangtze University) ;
  • Deng, Li (Department of General Surgery, The First Affiliated Hospital, Yangtze University)
  • Published : 2014.08.30

Abstract

MicroRNAs (miRNAs) act as critical regulators of genes involved in many biological processes. Aberrant alteration of miRNAs have been found in many cancers, including gastric cancer (GC), but the molecular mechanisms are not well understood. Herein, we investigated the role of miR-124 in GC. We found that its expression was significantly reduced in both GC tissue samples and cell lines. Forced expression of miR-124 suppressed GC cell proliferation, migration, and invasion. Furthermore, the Rho-associated protein kinase (ROCK1) was identified as a direct target of miR-124 in GC cells. Finally, silencing of ROCK1 showed similar effects as miR-124 overexpression, while supplementation of ROCK1 remarkably restored the cell growth and invasion inhibited by miR-124. Together, our data demonstrate that miR-124 acts as a tumor suppressor by targeting ROCK1, and posit miR-124 as a novel strategy for GC treatment.

Keywords

Gastric cancer;miR-124;ROCK1;proliferation;migration;invasion

References

  1. Chen G, Shen ZL, Wang L, et al (2013). Hsa-miR-181a-5p expression and effects on cell proliferation in gastric cancer. Asian Pac J Cancer Prev, 14, 3871-5. https://doi.org/10.7314/APJCP.2013.14.6.3871
  2. Chu D, Zhao Z, Li Y, et al (2014). Increased microRNA-630 expression in gastric cancer is associated with poor overall survival. PLoS One, 9, 90526. https://doi.org/10.1371/journal.pone.0090526
  3. DeSantis C, D Naishadham, A Jemal (2013). Cancer statistics for African Americans, 2013. CA Cancer J Clin, 63, 151-66. https://doi.org/10.3322/caac.21173
  4. Ding H, Wu YL, Wang YX, Zhu FF (2014). Characterization of the microRNA expression profile of cervical squamous cell carcinoma metastases. Asian Pac J Cancer Prev, 15, 1675-9. https://doi.org/10.7314/APJCP.2014.15.4.1675
  5. Hong L, Han Y, Yang J, et al (2014). MicroRNAs in gastrointestinal cancer: prognostic significance and potential role in chemoresistance. Expert Opin Biol Ther, 14, 1103-11. https://doi.org/10.1517/14712598.2014.907787
  6. Hsu TI, Hsu CH, Lee KH, et al (2014). MicroRNA-18a is elevated in prostate cancer and promotes tumorigenesis through suppressing STK4 in vitro and in vivo. Oncogenesis, 3, 99. https://doi.org/10.1038/oncsis.2014.12
  7. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  8. Lal A, Kim HH, Abdelmohsen K, et al (2008). p16(INK4a) translation suppressed by miR-24. PLoS One, 3, 1864. https://doi.org/10.1371/journal.pone.0001864
  9. Li J, Song Y, Wang Y, Luo J, Yu W (2013). MicroRNA-148a suppresses epithelial-to-mesenchymal transition by targeting ROCK1 in non-small cell lung cancer cells. Mol Cell Biochem, 380, 277-82. https://doi.org/10.1007/s11010-013-1682-y
  10. Li KK, Pang JC, Ching AK, et al (2009). miR-124 is frequently down-regulated in medulloblastoma and is a negative regulator of SLC16A1. Hum Pathol, 40, 1234-43. https://doi.org/10.1016/j.humpath.2009.02.003
  11. Li L, Luo J, Wang B, et al (2013). Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer. Mol Cancer, 12, 163. https://doi.org/10.1186/1476-4598-12-163
  12. Llaurado M, Majem B, Altadill T, et al (2014). MicroRNAs as prognostic markers in ovarian cancer. Mol Cell Endocrinol, 390, 73-84. https://doi.org/10.1016/j.mce.2014.03.006
  13. Lv Z, Yang L (2013). MiR-124 inhibits the growth of glioblastoma through the downregulation of SOS1. Mol Med Rep, 8, 345-9.
  14. Shin JY, Kim YI, Cho SJ, et al (2014). MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer. PLoS One, 9, 85205. https://doi.org/10.1371/journal.pone.0085205
  15. Wan X, Cheng Q, Peng R, et al (2014). ROCK1, a novel target of miR-145, promotes glioma cell invasion. Mol Med Rep, 9, 1877-82.
  16. Wang X, Yu H, Lu X, et al (2014). MiR-22 suppresses the proliferation and invasion of gastric cancer cells by inhibiting CD151. Biochem Biophys Res Commun, 445, 175-9. https://doi.org/10.1016/j.bbrc.2014.01.160
  17. Wen X, Ding L, Wang JJ, et al (2014). ROCK1 and LIM Kinase Modulate Retrovirus Particle Release and Cell-Cell Transmission Events. J Virol, 88, 6906-21. https://doi.org/10.1128/JVI.00023-14
  18. Wu YJ, Tang Y, Li ZF, et al (2013). Expression and significance of Rac1, Pak1 and Rock1 in gastric carcinoma. Asia Pac J Clin Oncol, 10, 33-9.
  19. Xia J, Guo X, Yan J, Deng K (2014). The role of miR-148a in gastric cancer. J Cancer Res Clin Oncol. [Epub ahead of print]
  20. Xia J, Wu Z, Yu C, et al (2012). miR-124 inhibits cell proliferation in gastric cancer through down-regulation of SPHK1. J Pathol, 227, 470-80. https://doi.org/10.1002/path.4030
  21. Xie L, Zhang Z, Tan Z, et al (2014). microRNA-124 inhibits proliferation and induces apoptosis by directly repressing EZH2 in gastric cancer. Mol Cell Biochem. [Epub ahead of print]
  22. Zhang C, Zhang S, Zhang Z, et al (2013). ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc. Oncogene. [Epub ahead of print]
  23. Zhang H, Wang Q, Zhao Q, Di W (2013). MiR-124 inhibits the migration and invasion of ovarian cancer cells by targeting SphK1. J Ovarian Res, 6, 84. https://doi.org/10.1186/1757-2215-6-84
  24. Zhang Y, Zheng L, Huang J, et al (2014). MiR-124 Radiosensitizes Human Colorectal Cancer Cells by Targeting PRRX1. PLoS One, 9, 93917. https://doi.org/10.1371/journal.pone.0093917
  25. Zhao WH, Wu SQ, Zhang YD (2013). Downregulation of miR- 124 promotes the growth and invasiveness of glioblastoma cells involving upregulation of PPP1R13L. Int J Mol Med, 32, 101-7.
  26. Zhou P, Huang G, Zhao Y, et al (2014). MicroRNA-363-mediated downregulation of S1PR1 suppresses the proliferation of hepatocellular carcinoma cells. Cell Signal, 26, 1347-54. https://doi.org/10.1016/j.cellsig.2014.02.020
  27. Zhou X, Wei M, Wang W (2013). MicroRNA-340 suppresses osteosarcoma tumor growth and metastasis by directly targeting ROCK1. Biochem Biophys Res Commun, 437, 653-8. https://doi.org/10.1016/j.bbrc.2013.07.033

Cited by

  1. MicroRNA-144 inhibits migration and proliferation in rectal cancer by downregulating ROCK-1 vol.12, pp.5, 2015, https://doi.org/10.3892/mmr.2015.4391
  2. Association between the DICER rs1057035 Polymorphism and Cancer Risk: Evidence from a Meta-analysis of 1,2675 Individuals vol.16, pp.1, 2015, https://doi.org/10.7314/APJCP.2015.16.1.119
  3. MicroRNAs May Serve as Emerging Molecular Biomarkers for Diagnosis and Prognostic Assessment or as Targets for Therapy in Gastric Cancer vol.16, pp.12, 2015, https://doi.org/10.7314/APJCP.2015.16.12.4813
  4. MicroRNA-124 rs531564 Polymorphism and Cancer Risk: A Meta-analysis vol.16, pp.17, 2015, https://doi.org/10.7314/APJCP.2015.16.17.7905
  5. miR-124 interacts with the Notch1 signalling pathway and has therapeutic potential against gastric cancer vol.20, pp.2, 2015, https://doi.org/10.1111/jcmm.12724
  6. miR-124 inhibits cell proliferation, migration and invasion by directly targeting SOX9 in lung adenocarcinoma vol.35, pp.5, 2016, https://doi.org/10.3892/or.2016.4648
  7. Novel Insights into the Roles of Rho Kinase in Cancer vol.64, pp.4, 2016, https://doi.org/10.1007/s00005-015-0382-6
  8. miR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ β-catenin/EMT signaling cascade in gastric cancer vol.17, pp.1, 2017, https://doi.org/10.1186/s12885-017-3875-3
  9. MicroRNA-124 suppresses proliferation and glycolysis in non–small cell lung cancer cells by targeting AKT–GLUT1/HKII vol.39, pp.5, 2017, https://doi.org/10.1177/1010428317706215
  10. Inhibition of the Hedgehog signaling pathway suppresses cell proliferation by regulating the Gli2/miR-124/AURKA axis in human glioma cells vol.50, pp.5, 2017, https://doi.org/10.3892/ijo.2017.3946
  11. In vivo and in vitro effects of microRNA-124 on human gastric cancer by targeting JAG1 through the Notch signaling pathway pp.07302312, 2017, https://doi.org/10.1002/jcb.26413
  12. ROCK1-PredictedmicroRNAs Dysregulation Contributes to Tumor Progression in Ewing Sarcoma pp.1532-2807, 2017, https://doi.org/10.1007/s12253-017-0374-4
  13. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer vol.17, pp.6, 2016, https://doi.org/10.3390/ijms17060945
  14. Proposed Molecular and miRNA Classification of Gastric Cancer vol.19, pp.6, 2018, https://doi.org/10.3390/ijms19061683