Oncogenic miR-1825 promotes head and neck carcinogenesis via targeting FREM1


Capik O., GÜNDOĞDU B., TATAR A., ŞAHİN A., Chen F., Creighton C. J., ...Daha Fazla

JOURNAL OF CELLULAR BIOCHEMISTRY, cilt.124, sa.10, ss.1628-1645, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 124 Sayı: 10
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/jcb.30473
  • Dergi Adı: JOURNAL OF CELLULAR BIOCHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Veterinary Science Database
  • Sayfa Sayıları: ss.1628-1645
  • Anahtar Kelimeler: head and neck squamous cell carcinoma, miR-1825, oncogene, SQUAMOUS-CELL CARCINOMA, EMBRYONIC STEM-CELLS, EXPRESSION, CANCER, PROLIFERATION, MICRORNAS, 20Q11.21, SURVIVAL
  • Atatürk Üniversitesi Adresli: Evet

Özet

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant cancer type worldwide. Although the therapeutic modalities currently used for patients with HNSCC improved in recent decades, HNSCC prognosis is still poor. Therefore, it is an urgent necessity to understand the pathogenesis of HNSCC, to develop novel and effective treatment strategies, and to characterize and identify the oncogenes that are responsible for an aggressive HNSCC phenotype. In this study, we aimed to better understand the roles of miR-1825 in the pathogenesis of HNSCC. We examined the impacts of miR-1825 deregulation on the cancer-associated phenotypes using in vitro tests evaluating cell viability, clonogenicity, cell migration, invasion, apoptosis, and stem cell characteristics. In addition, we investigated the effects of miR-1825 overexpression on the tumor formation capacity of head and neck cancer cells in vivo using nude mice. We searched for potential targets of miR-1825 using microarray analysis and luciferase assay. We found that miR-1825 expression is upregulated in head and neck cells and clinical tumor samples in comparison to corresponding controls, where it potentially acts as an oncogene. We, then, showed that ectopic miR-1825 overexpression promotes cellular phenotypes related to head and neck cancer progression in vitro and has a stimulating potential on cancer formation in vivo. We also identified FREM1 as a direct target of miR-1825 and demonstrated its reduced expression in HNSCC samples using immunohistochemistry analysis. Collectively, we suggest that the miR-1825/FREM1 axis serves as an important mediator of HNSCC development, where miR-1825 acts as an oncogene.