Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

p53R248Q Induces Invasion and Migration Through Overexpression of miR-182-5p in Cancer

Version 1 : Received: 11 July 2023 / Approved: 12 July 2023 / Online: 12 July 2023 (12:10:37 CEST)

A peer-reviewed article of this Preprint also exists.

Madrigal, T.; Ortega-Bernal, D.; Herrera, L.A.; González-De la Rosa, C.H.; Domínguez-Gómez, G.; Aréchaga-Ocampo, E.; Díaz-Chávez, J. Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells. Cells 2023, 12, 2506. Madrigal, T.; Ortega-Bernal, D.; Herrera, L.A.; González-De la Rosa, C.H.; Domínguez-Gómez, G.; Aréchaga-Ocampo, E.; Díaz-Chávez, J. Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells. Cells 2023, 12, 2506.

Abstract

Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function. Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) in the Saos-2 cell line (null p53) transfected as compared with p53WT transfected cells. The association between these miRNAs and the signaling pathways in which they might participate was performed through the miRPath Software. QRT-PCR was employed to validate the miRNAs profiles. In addition, we explored if the induction of cell migration and invasion by the p53R48Q mutant was dependent on the miR-182-5p. We observed that p53 mutants have an overall negative effect on miRNA expression. Likewise, we found miRNAs differentially expressed associated with regulating Oncogenic signaling pathways. We found overexpression of miR-182-5p, which is associated with processes such as cell migration and invasion. Inhibition of mutant p53R248Q and miR-182-5p increased FOXF2-MTSS1 levels and decreased cell migration and invasion. Our results suggest that p53 mutants increase the expression of miR-182-5p, and this miRNA is also necessary to induce cell migration and invasion by the p53R248Q mutant in a cancer cell model.

Keywords

miRNAs; Mutant p53; Gain of function; Cancer

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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