microRNA-100 inhibits cell division in human non-small cell lung cancer via a CDC25A signaling mechanism.

Lung cancer is one of the most common malignancies worldwide, and the prognosis remains unsatisfactory with conventional treatments. Our research revealed that miR-100 is significantly decreased in non-small cell lung cancer (NSCLC) tissues and cell lines, indicating its potential role in NSCLC development. The upregulation of miR-100 expression inhibited the growth of L18 NSCLC cells, while its downregulation increased the growth of A549 NSCLC cells. Cell cycle dysregulation is a key factor in NSCLC development. CDC25A is a vital cell cycle regulator that promotes cell cycle progression. Our objective was to determine the function of the CDC25A protein and its effect on the prognosis of NSCLC patients. The luciferase reporter gene assay demonstrated direct targeting of the 3' non-coding sequence of CDC25A by miR-100-3p. Western blot analysis confirmed that the protein expression levels of cyclin D1, CDK6, pRb, and E2F3 decreased upon miR-100 overexpression. Furthermore, cell cycle analysis demonstrated that miR-100 overexpression led to G1 phase arrest and a concomitant reduction in S phase entry in NSCLC cells. In vivo studies using a xenograft mouse model demonstrated that miR-100 overexpression inhibited tumor growth, while its inhibition accelerated it. Rescue experiments confirmed that CDC25A partially reversed the cell cycle arrest and growth suppression mediated by miR-100. This study's findings suggest that miR-100 can inhibit NSCLC progression by specifically targeting CDC25A, a cell cycle regulator, and its downstream molecular targets. Hence, miR-100 may have significant therapeutic potential against NSCLC.