miR-509-5p promotes colorectal cancer cell ferroptosis by targeting SLC7A11.

Autor: Elrebehy MA; Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt. Electronic address: mahmoud.elrebeihy@buc.edu.eg., Abdelghany TM; Department of Pharmacology and Toxicology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo 11231, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt., Elshafey MM; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt., Gomaa MH; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt., Doghish AS; Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt. Electronic address: ahmed_doghish@azhar.edu.eg.
Jazyk: angličtina
Zdroj: Pathology, research and practice [Pathol Res Pract] 2023 Jul; Vol. 247, pp. 154557. Date of Electronic Publication: 2023 May 20.
DOI: 10.1016/j.prp.2023.154557
Abstrakt: Background/aim: Colorectal cancer (CRC), is characterized by aberrant microRNA (miRNA) expression during their development and progression. Recently, miR-509-5p's role as a regulator of several malignancies has been highlighted. Its function in CRC, however, is exposed. This research aimed to determine the relative abundance of miR-509-5p and its biological function in colorectal cancer.
Methods: The expression of miR-509-5p in CRC cell lines and tissues, as well as neighboring normal tissues, was evaluated using real-time quantitative polymerase chain reaction (RT-PCR). 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-2 H-tetrazolium bromide (MTT) was used to assess cell viability. The association between miR-509-5p and its predicted target in CRC cells was analyzed using bioinformatics tools. The levels of Solute carrier family seven number 11 (SLC7A11) were assessed using enzyme-linked immunosorbent assay (ELISA), while malondialdehyde (MDA) and iron content levels were determined colorimetrically.
Results: Compared to adjacent normal tissue and normal colorectal cell, there was a significant reduction in miR-509-5p expression in both CRC tissues and cells. miR-509-5p upregulation inhibited Caco-2 cell viability. SLC7A11 was predicted to be the cellular target of miR-509-5p. Interestingly, miR-509-5p's overexpression suppressed both mRNA and protein levels of SLC7A11, whereas its downregulation boosted SLC7A11 gene expression. Finally, overexpressing miR-509-5p resulted in increased MDA and iron levels.
Conclusion: Our results demonstrate that miR-509-5p has CRC tumor suppressor functions through controlling the expression of SLC7A11 and promotion of ferroptosis providing a new therapeutic target for the treatment of CRC.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors have declared that no competing interests exist.
(Copyright © 2023 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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