Investigating the effectiveness of miR-4477a and metformin in regulating PD-L1, an immune checkpoint in colorectal cancer

Tülüce Y., Köstekci S.

Gene Reports, cilt.45, 2026 (ESCI, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 45
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.genrep.2026.102656
  • Dergi Adı: Gene Reports
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE
  • Anahtar Kelimeler: Colorectal cancer, Immune checkpoint, Immunotherapy, miR-4477a, PD-L1
  • Van Yüzüncü Yıl Üniversitesi Adresli: Evet

Özet

The study investigated suppressing the PD-L1 ligand, which plays a significant role in immunotherapy and is evaded by cancer cells, in colorectal cancer cells (HCT-116), using as independent interventions of miR-4477a or metformin. To achieve this objective, multi-database bioinformatics analyses were performed to identify potential candidate microRNAs (miRNAs) predicted to target the CD274 (PD-L1) mRNA transcript. The results of this analysis revealed that the mimic version of the microRNA, miR-4477a, possesses this activity. Consequently, KEGG and GO bioinformatics analyses were employed to identify the molecular pathways, signaling pathways, and cellular components affected by this microRNA within the cell. In order to validate the bioinformatics data, an MTT assay was used to determine the in vitro cytotoxic effect on HCT-116, and an ELISA assay was used to measure PD-L1 protein levels. Cellular analysis revealed that both the microRNA molecule, miR-4477a, and the drug metformin exhibited cytotoxic effects on colon cancer cells. It has been demonstrated that the application of miR-4477a at various doses results in a relative decrease in PD-L1 levels. Within the concept of drug repurposing, given metformin's cytotoxic effect and its anti-PD-L1 properties -albeit limited-the individual applications of miR-4477a or metformin exhibit promising cytotoxic and anti-PD-L1 properties in colorectal cancer cells may have a promising effect in further and more detailed studies.