miR‐4429 sensitized cervical cancer cells to irradiation by targeting RAD51

Abstract

Cervical cancer (CC) is a prevalent malignancy in women, with the feature of metastasis and easy recurrence is responsible for a large proportion of global cancer deaths. Radiotherapy is one of the common treatment tools for CC patients with unresectable tumors. However, radio‐resistance in patients could be a major reason for recurrence. Therefore, it is of significance to tunnel the molecular mechanism of radio‐resistance in CC. MicroRNAs (miRNAs) are increasingly reported in the regulation of cancer progression and cellular response to radiotherapy and chemotherapy. miR‐4429 is a newly discovered miRNA acting as a tumor‐suppressor gene in multiple cancers, but its function in CC has never been explored yet. The current study tried to explore the role of miR‐4429 in cell radio‐sensitivity in CC. First, we validated the downregulation of miR‐4429 in CC cells. Importantly, the association of miR‐4429 with radio‐resistance was validated by identifying the downregulation of miR‐4429 in radio‐resistant CC cells. Gain‐ and loss‐of‐function assays validated that miR‐4429 sensitized CC cells to irradiation. Through bioinformatics tools, RAD51 recombinase (RAD51) was identified to be a target for miR‐4429. RAD51 is known to be a crucial regulator for DNA damage repair and has been reported to influence cell radio‐resistance in cancers, including in CC. Luciferase reporter assay confirmed the interaction between miR‐4429 and RAD51. Finally, rescue assays indicated that miR‐4429 promoted CC cell radio‐sensitivity through RAD51. Consequently, our study showed that miR‐4429 sensitized CC cells to irradiation by targeting RAD51, providing a potential therapeutic target for CC patients.