Abstract 6685: miR-148a-3p acts as a potential radiosensitizer through integrin signaling pathway in head and neck cancer

Abstract Radioresistance remains an unsolved challenge in cancer treatments and links to radiation-induced bystander effects (RIBEs), hence facilitating tumorigenesis or metastasis. In our previous study, miR-148a-3p expression in plasma from head and neck cancer patients was related to radiotherapy. This study explored the roles of miR-148a-3p in radiation response and RIBEs while introducing a radiosensitizer in head and neck cancer. Radiation for cultured cells was provided by the Radiation Oncology Department at Landseed International Hospital. The in vitro study demonstrated how miR-148a-3p regulates cancer cell functions and DNA damage responses. Exosomes were isolated from conditioned media (CM) using chromatographic columns. To generate the radiosensitizer, exosomes from Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) were combined with miR-148a-3p mimics and sonicated. Following radiation, miR-148a-3p expression was decreased. The gain-of-function studies revealed that miR-148a-3p enhanced radiosensitivity by reducing cell proliferation and migration after radiation, promoting DNA damage and genomic instability, and inducing the G2/M phase arrest. Conversely, the miR-148a-3p sponges diminished the radiosensitivity of cancer cells. Furthermore, we perceived that miR-148a-3p was implicated in the RIBEs. Specifically, high miR-148a-3p levels in CM from irradiated cells effectively inhibited the RIBE-induced proliferation and migration of non-irradiated cancer cells. Consequently, we observed increased levels of miR-148a-3p in exosomes secreted by irradiated cells if we overexpressed miR-148a-3p mimics and exosomal miR-148a-3p suppressed cell migration and invasion, and also promoted DNA damage and genomic instability in non-irradiated cancer cells. In addition, the luciferase assay revealed that ITGA5, a member of integrin receptor family involved in various malignancies, is a direct target of miR-148a-3p. The upregulation of ITGA5 counteracted the radiosensitivity of miR-148a-3p, while ITGA5 knockdown increased radiation sensitivity. Finally, miR-148a-3p was loaded into WJMSC-derived exosomes to develop a radiosensitizer agent, which eliminated cancer cell migration during radiotherapy. This research indicated that miR-148a-3p enhanced the radiosensitivity and prevented RIBE activities in head and neck cancer cells by regulating ITGA5, suggesting a promising therapeutic radiosensitizer for head and neck cancer. Citation Format: Thien-Hoang Pham, Ming-Hua Wang, Tai-Yu Kuo, An-Lun Li, Kun-Lin Wu, Ching-Yun Chen, Nianhan Ma. miR-148a-3p acts as a potential radiosensitizer through integrin signaling pathway in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6685.