miR-5088-5p inhibitor reduces radiation-induced malignancy by decreasing Slug

Abstract

Abstract Purpose Radiotherapy is widely used for cancer treatment, but paradoxically, surviving cancer cells can become malignant, leading to tumor recurrence or metastasis. Therefore, in order to increase the effectiveness of radiotherapy, efforts to reduce radiation-induced malignancy are absolutely necessary. As a tool, microRNA simultaneously regulates the expression of multiple target mRNAs, so it has significant potential as an effective therapeutic agent. The main objective of this study is to elucidate the malignant mechanism of radiation-induced miR-5088-5p and to prove the efficacy of miR-5088-5p inhibitor for mitigating malignancy, thereby demonstrating its applicability as a therapeutic agent to increase the efficiency of radiotherapy. Methods To analyze the relationship between radiation and miR-5088-5p expression, miR-5088-5p levels were determined by qRT-PCR in the plasma of breast and lung cancer patients with or without radiotherapy. MSP and qMSP assays were used to confirm the methylation of radiation-induced miR-5088-5p. To determine whether miR-5088-5p inhibitor reduces radiation-induced malignancy by decreasing Slug, we used wound healing, invasion, sphere formation, Western blot, qRT-PCR assays, and in vivo mouse xenograft metastatic model. Results It was confirmed at both the cellular and animal model that miR-5088-5p, which showed higher expression in the plasma of breast cancer and lung cancer patients with radiotherapy, enhances tumor malignancy by enhancing its expression through hypomethylation of its promoter by radiation. On the other hand, it was shown that miR-5088-5p inhibitor reduced the mechanism of radiation-induced malignancy. Conclusions Collectively, miR-5088-5p inhibitors have shown potential as a combination therapy to enhance radiotherapy effectiveness by reducing radiation-induced malignancy.