MiR-509–5p promotes colorectal cancer cell ferroptosis by targeting SLC7A11

Abstract

Background/AimColorectal 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. MethodsThe 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. ResultsCompared 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. ConclusionOur 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.