Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Overexpression of microRNA-612 Restrains the Growth, Invasion, and Tumorigenesis of Melanoma Cells by Targeting Espin

  • Zhu, Ying (Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University) ;
  • Zhang, Hao-liang (Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University) ;
  • Wang, Qi-ying (Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University) ;
  • Chen, Min-jing (Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University) ;
  • Liu, Lin-bo (Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University)
  • Received : 2017.09.22
  • Accepted : 2017.11.24
  • Published : 2018.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.

Keywords

References

  1. Alaoui-Jamali, M.A., Bismar, T.A., Gupta, A., Szarek, W.A., Su, J., Song, W., Xu, Y., Xu, B., Liu, G., Vlahakis, J.Z., et al. (2009). A novel experimental heme oxygenase-1-targeted therapy for hormonerefractory prostate cancer. Cancer Res. 69, 8017-8024. https://doi.org/10.1158/0008-5472.CAN-09-0419
  2. Deacu, E., Mori, Y., Sato, F., Yin, J., Olaru, A., Sterian, A., Xu, Y., Wang, S., Schulmann, K., Berki, A., et al. (2004). Activin type II receptor restoration in ACVR2-deficient colon cancer cells induces transforming growth factor-beta response pathway genes. Cancer Res. 64, 7690-7696. https://doi.org/10.1158/0008-5472.CAN-04-2082
  3. Donaudy, F., Zheng, L., Ficarella, R., Ballana, E., Carella, M., Melchionda, S., Estivill, X., Bartles, J.R., and Gasparini, P. (2006). Espin gene (ESPN) mutations associated with autosomal dominant hearing loss cause defects in microvillar elongation or organisation. J. Med. Genet. 43, 157-161.
  4. Cheerla, N., and Gevaert, O. (2017). MicroRNA based Pan-Cancer diagnosis and treatment recommendation. BMC Bioinformatics. 18, 32. https://doi.org/10.1186/s12859-016-1421-y
  5. Fahrioglu, U., Dodurga, Y., Elmas, L., and Secme, M. (2016). Ferulic acid decreases cell viability and colony formation while inhibiting migration of MIA PaCa-2 human pancreatic cancer cells in vitro. Gene 576, 476-482. https://doi.org/10.1016/j.gene.2015.10.061
  6. Li, B., Xie, Z., Li, Z., Chen, S., and Li, B. (2016). MicroRNA-613 targets FMNL2 and suppresses progression of colorectal cancer. Am. J. Transl. Res. 8, 5475-5484.
  7. Liu, Y., Liu, D.L., Dong, L.L., Wen, D., Shi, D.M., Zhou, J., Fan, J., and Wu, W.Z. (2016). miR-612 suppresses stem cell-like property of hepatocellular carcinoma cells by modulating Sp1/Nanog signaling. Cell Death Dis. 7, e2377. https://doi.org/10.1038/cddis.2016.282
  8. Kircher, D.A., Silvis, M.R., Cho, J.H., and Holmen, S.L. (2016). Melanoma Brain Metastasis: Mechanisms, Models, and Medicine. Int. J. Mol. Sci. 17(9). pii: E1468. https://doi.org/10.3390/ijms17091468
  9. Komina, A., Palkina, N., Aksenenko, M., Tsyrenzhapova, S., and Ruksha, T. (2016). Antiproliferative and Pro-Apoptotic Effects of MiR-4286 Inhibition in Melanoma Cells. PLoS One 11, e0168229. https://doi.org/10.1371/journal.pone.0168229
  10. Mao, Y., Shen, J., Lu, Y., Lin, K., Wang, H., Li, Y., Chang, P., Walker, M.G., and Li, D. (2017). RNA sequencing analyses reveal novel differentially expressed genes and pathways in pancreatic cancer. Oncotarget 8, 42537-42547.
  11. Pal, H.C., Hunt, K.M., Diamond, A., Elmets, C.A., and Afaq, F. (2016). Phytochemicals for the Management of Melanoma. Mini. Rev. Med. Chem. 16, 953-979. https://doi.org/10.2174/1389557516666160211120157
  12. Sekerkova, G., Zheng, L., Loomis, P.A., Mugnaini, E., and Bartles, J.R. (2006). Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli. Cell Mol. Life Sci. 63, 2329-2341. https://doi.org/10.1007/s00018-006-6148-x
  13. Sheng, L., He, P., Yang, X., Zhou, M., and Feng, Q. (2015). miR-612 negatively regulates colorectal cancer growth and metastasis by targeting AKT2. Cell Death Dis. 6, e1808. https://doi.org/10.1038/cddis.2015.184
  14. Shu, X., Hildebrandt, M.A., Gu, J., Tannir, N.M., Matin, S.F., Karam, J.A., Wood, C.G., and Wu, X. (2017). MicroRNA profiling in clear cell renal cell carcinoma tissues potentially links tumorigenesis and recurrence with obesity. Br. J. Cancer. 116, 77-84. https://doi.org/10.1038/bjc.2016.392
  15. Tang, J., Tao, Z.H., Wen, D., Wan, J.L., Liu, D.L., Zhang, S., Cui, J.F., Sun, H.C., et al. (2014). MiR-612 suppresses the stemness of liver cancer via Wnt/${\beta}$-catenin signaling. Biochem. Biophys. Res. Commun. 447, 210-215. https://doi.org/10.1016/j.bbrc.2014.03.135
  16. Tao, Z.H., Wan, J.L., Zeng, L.Y., Xie, L., Sun, H.C., Qin, L.X., Wang, L., Zhou, J., Ren, Z.G., Li, Y.X., et al. (2013). miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma. J. Exp. Med. 210, 789-803. https://doi.org/10.1084/jem.20120153
  17. Tas, F. (2012). Metastatic behavior in melanoma: timing, pattern, survival, and influencing factors. J. Oncol. 2012, 647684.
  18. Taura, A., Taura, K., Koyama, Y., Yamamoto, N., Nakagawa, T., Ito, J., and Ryan, A.F. (2016). Hair cell stereociliary bundle regeneration by espin gene transduction after aminoglycoside damage and hair cell induction by Notch inhibition. Gene Ther. 23, 415-423. https://doi.org/10.1038/gt.2016.12
  19. van Akkooi, A.C., Atkins, M.B., Agarwala, S.S., and Lorigan, P. (2016). Surgical Management and Adjuvant Therapy for High-Risk and Metastatic Melanoma. Am. Soc. Clin. Oncol. Educ. Book. 35, e505-e514.
  20. Wang, L., Zou, J., Shen, Z., Song, E., and Yang, J. (2012). Whirlin interacts with espin and modulates its actin-regulatory function: an insight into the mechanism of Usher syndrome type II. Hum. Mol. Genet. 21, 692-710. https://doi.org/10.1093/hmg/ddr503
  21. Waters, A.M., Stewart, J.E., Atigadda, V.R., Mroczek-Musulman, E., Muccio, D.D., Grubbs, C.J., and Beierle, E.A. (2015). Preclinical Evaluation of a Novel RXR Agonist for the Treatment of Neuroblastoma. Mol. Cancer Ther. 14, 1559-1569. https://doi.org/10.1158/1535-7163.MCT-14-1103
  22. Xu, D., Chen, X., He, Q., and Luo, C. (2016). MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1. Onco. Targets Ther. 9, 7047-7057. https://doi.org/10.2147/OTT.S107235
  23. Yanagishita, T., Yajima, I., Kumasaka, M., Kawamoto, Y., Tsuzuki, T., Matsumoto, Y., Watanabe, D., and Kato, M. (2014). Actin-binding protein, Espin: a novel metastatic regulator for melanoma. Mol. Cancer Res. 12, 440-446. https://doi.org/10.1158/1541-7786.MCR-13-0468-T
  24. Zhang, K., Wu, X., Wang, J., Lopez, J., Zhou, W., Yang, L., Wang, S.E., Raz, D.J., and Kim, J.Y. (2016). Circulating miRNA profile in esophageal adenocarcinoma. Am. J. Cancer Res. 6, 2713-2721.
  25. Zheng, L., Sekerkova, G., Vranich, K., Tilney, L.G., Mugnaini, E., and Bartles, J.R. (2000). The deaf jerker mouse has a mutation in the gene encoding the espin actin-bundling proteins of hair cell stereocilia and lacks espins. Cell 102, 377-385. https://doi.org/10.1016/S0092-8674(00)00042-8

Cited by

  1. An actin-binding protein ESPN is an independent prognosticator and regulates cell growth for esophageal squamous cell carcinoma vol.18, pp.None, 2018, https://doi.org/10.1186/s12935-018-0713-x
  2. Metformin Treatment Suppresses Melanoma Cell Growth and Motility through Modulation of microRNA Expression vol.11, pp.2, 2018, https://doi.org/10.3390/cancers11020209
  3. NFKB1-miR-612-FAIM2 pathway regulates tumorigenesis in neurofibromatosis type 1 vol.55, pp.7, 2018, https://doi.org/10.1007/s11626-019-00370-3
  4. MicroRNA‐612 inhibits cervical cancer progression by targeting NOB1 vol.24, pp.5, 2018, https://doi.org/10.1111/jcmm.14985
  5. Simultaneous microRNA-612 restoration and 5-FU treatment inhibit the growth and migration of human PANC-1 pancreatic cancer cells vol.20, pp.None, 2018, https://doi.org/10.17179/excli2020-2900
  6. Actin-Binding Proteins as Potential Biomarkers for Chronic Inflammation-Induced Cancer Diagnosis and Therapy vol.2021, pp.None, 2018, https://doi.org/10.1155/2021/6692811