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Up-Regulation of Kiss1 As a Novel Target of Let-7I in Melanoma Serves As a Potential Suppressor of Migration and Proliferation in Vitro Publisher Pubmed



Alkafaji HA1 ; Raji A1 ; Rahman HS2 ; Zekiy AO3 ; Adili A4 ; Jalili M5 ; Hojjatipour T6 ; Cidarregui A7 ; Shomali N5, 8 ; Tarzi S5 ; Tamjidifar R5 ; Heshmati R5 ; Marofi F8 ; Akbari M5 Show All Authors
Authors
  1. Alkafaji HA1
  2. Raji A1
  3. Rahman HS2
  4. Zekiy AO3
  5. Adili A4
  6. Jalili M5
  7. Hojjatipour T6
  8. Cidarregui A7
  9. Shomali N5, 8
  10. Tarzi S5
  11. Tamjidifar R5
  12. Heshmati R5
  13. Marofi F8
  14. Akbari M5
  15. Hasanzadeh A8
  16. Deljavanghodrati M5
  17. Jarahian M9
  18. Sandoghchian Shotorbani S5, 8
Show Affiliations
Authors Affiliations
  1. 1. College of medicine, University of Babylon, Babylon, Iraq
  2. 2. Department of Physiology, College of Medicine, University of Suleimanyah, Suleimanyah, Iraq
  3. 3. Sechenov First Moscow State Medical University, Moscow, Russian Federation
  4. 4. Department of Oncology, Tabriz University of Medical Sciences, Tabriz, Iran
  5. 5. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  6. 6. Department of Hematology and Blood Transfusion, Students Research Centre, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Targeted Tumor Vaccines Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
  8. 8. Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran
  9. 9. Toxicology and Chemotherapy Unit (G401), German Cancer Research Center, Heidelberg, Germany

Source: Journal of Cellular and Molecular Medicine Published:2021


Abstract

Melanoma is a kind of skin cancer that is begun by the alteration of melanocytes. miRNAs are small non-coding RNA molecules that regulate a variety of biological processes. KISS1, the metastasis-suppressor gene, encodes kisspeptins which inhibits migration and proliferation of cancers. This study was aimed to determine the role of Let-7i and KISS1 in melanoma cell migration and proliferation. At first, the expression of Let-7i and KISS1 was determined in patients with melanoma. In the in vitro part of the study, Let-7i mimics were transfected and the impact of its restoration on target gene expression, proliferation, migration and apoptosis of SK-MEL-3 melanoma cell line was assessed by real-time PCR and Western blotting, MTT assay, wound-healing assay and flow cytometry, respectively. Besides, KISS1 inhibitor siRNA alone and along with Let-7i was transfected to determine their probable correlation. The results revealed that either Let-7i or KISS1 were down-regulated in patients with melanoma. The results obtained from the in vitro part of the study revealed that restoration of Let-7i reduced the expression of metastasis- and proliferation-related target genes. Moreover, it was revealed that up-regulation of Let-7i attenuated migration and proliferation capability of SK-MEL-3 cells. Besides, it was demonstrated that Let-7i restoration induced apoptosis in melanoma cells. More importantly, the KISS1 inhibitor caused a prominent cell migration and proliferation, attenuated by Let-7i re-expression. To sum up, the present study revealed the impressive role of Let-7i restoration along with its correlation with KISS1 on melanoma carcinogenicity which may be applicable in future in vivo studies. © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.