Downregulation of miR‑10b‑5p facilitates the proliferation of uterine leiomyosarcoma cells: A microRNA sequencing‑based approach

Oncol Rep. 2023 May;49(5):86. doi: 10.3892/or.2023.8523. Epub 2023 Mar 17.

Abstract

Uterine leiomyosarcoma (ULMS) is one of the most aggressive gynecological malignancies. In addition, the molecular background of ULMS has not been fully elucidated due to its low incidence. Therefore, no effective treatment strategies have been established based on its molecular background. The present study aimed to investigate the roles of microRNAs (miRNAs/miRs) in the development of ULMS. Comprehensive miRNA sequencing was performed using six ULMS and three myoma samples, and revealed 53 and 11 significantly upregulated and downregulated miRNAs, respectively. One of the most abundant miRNAs in myoma samples was miR‑10b‑5p. The mean normalized read count of miR‑10b‑5p was 93,650 reads in myoma, but only 27,903 reads in ULMS. Subsequently, to investigate the roles of miR‑10b‑5p, gain‑of‑function analysis was performed using SK‑UT‑1 and SK‑LMS‑1 cell lines. The overexpression of miR‑10b‑5p suppressed cell proliferation and reduced the number of colonies. Moreover, miR‑10b‑5p increased the number of cells in the G1 phase. In conclusion, tumor‑suppressive miR‑10b‑5p was significantly downregulated in ULMS compared with in myoma; thus, miR‑10b‑5p may serve a specific role in sarcoma progression.

Keywords: cell cycle; miR‑10b‑5p; microRNA sequencing; proliferation; uterine leiomyosarcoma.

MeSH terms

  • Aged
  • Cell Line
  • Cell Proliferation / genetics
  • Down-Regulation*
  • Female
  • G1 Phase
  • Genes, Tumor Suppressor
  • Humans
  • Leiomyosarcoma* / genetics
  • Leiomyosarcoma* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Myoma / genetics
  • Myoma / pathology
  • Sequence Analysis, RNA
  • Uterine Neoplasms* / genetics
  • Uterine Neoplasms* / pathology

Substances

  • MicroRNAs

Grants and funding

This study was supported by JSPS KAKENHI (grant nos. 21H02721, 21H03075 and 21K16789) and the Fusion Oriented Research for Disruptive Science and Technology (FOREST) from Japan Science and Technology Agency (JST). Moreover, this study was supported by the YOKOYAMA Foundation for Clinical Pharmacology (grant no. YRY-2115), the Princess Takamatsu Cancer Research Fund (grant no. 20-25237), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (grant no. 202102016), Daiichi Sankyo Foundation of Life Science (grant no. 2021HrCK), the Uehara Memorial Foundation (grant no. 202110201), the Japan Research Foundation for Clinical Pharmacology (grant no. 2021A18), and the Foundation for Promotion of Cancer Research in Japan.