Downregulation of matrix metalloproteinase 14 by the antitumor miRNA, miR-150-5p, inhibits the aggressiveness of lung squamous cell carcinoma cells

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Bibliographic Information

Title
Downregulation of matrix metalloproteinase 14 by the antitumor miRNA, miR-150-5p, inhibits the aggressiveness of lung squamous cell carcinoma cells
Other Title
  • 癌抑制型マイクロRNA(miR-150-5p)はmatrix metalloproteinase 14 を制御して肺扁平上皮癌の増悪を抑制する
Author
Suetsugu, Takayuki
Alias Name
  • 末次, 隆行
  • スエツグ, タカユキ
University
鹿児島大学
Types of degree
博士(医学)
Grant ID
甲総研第559号
Degree year
2020-03-12

Description

In the present study, in order to elucidate the aggressive nature of lung squamous cell carcinoma (LUSQ), we investigated the oncogenic RNA networks regulated by antitumor microRNAs (miRNAs or miRs) in LUSQ cells. The analysis of our original miRNA expression signatures of human cancers revealed that microRNA‑150‑5p (miR‑150‑5p) was downregulated in various types of cancer, indicating that miR‑150‑5p acts as an antitumor miRNA by targeting several oncogenic genes. Thus, the aims of this study were to investigate the antitumor roles of miR‑150‑5p in LUSQ cells and to identify oncogenes regulated by miR‑150‑5p that are involved in the aggressive behavior of LUSQ. The downregulation of miR‑150‑5p was validated in clinical samples of LUSQ and cell lines (SK-MES‑1 and EBC‑1). The ectopic overexpression of miR‑150‑5p significantly suppressed cancer cell aggressiveness. Comprehensive gene expression analyses revealed that miR‑150‑5p regulated 9 genes in the LUSQ cells. Among these, matrix metalloproteinase 14 (MMP14) was found to be a direct target of miR‑150‑5p, as shown by luciferase reporter assay. The knockdown of MMP14 using siRNA against MMP14 (si-MMP14) significantly inhibited cancer cell migration and invasion. The overexpression of MMP14 was detected in clinical specimens of LUSQ by immunohistochemistry. On the whole, these findings suggest that the downregulation of miR‑150‑5p and the overexpression of MMP14 may be deeply involved in the pathogenesis of LUSQ. Takayuki Suetsugu, Keiichi Koshizuka, Naohiko Seki, Keiko Mizuno, Atsushi Okato, Takayuki Arai, Shunsuke Misono, Akifumi Uchida, Tomohiro Kumamoto, Hiromasa Inoue Downregulation of matrix metalloproteinase 14 by the antitumor miRNA, miR‑150‑5p, inhibits the aggressiveness of lung squamous cell carcinoma cells International Journal of Oncology 2018 52(3) 913-924 https://doi.org/10.3892/ijo.2017.4232

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2024-01-19 再収集

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