miR-339-5p Increases Radiosensitivity of Lung Cancer Cells by Targeting Phosphatases of Regenerating Liver-1 (PRL-1)
Jia Wang, Mawei Jiang, Shian Xia
(Department of Oncology, Xinhua Hospital Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China (mainland))
Med Sci Monit 2018; 24:8408-8416
Radiotherapy is the most effective non-surgical modality in lung cancer treatment, and microRNAs (miRNAs) have been suggested as key regulators in radiosensitization. Herein, we explored the specific function of miR-339-5p in the radiosensitivity of lung cancer cells.
MATERIAL AND METHODS: Radiosensitivity was assessed by cell viability (CCK-8 assay), cell apoptosis, and cell cycle changes (flow cytometry). qRT-PCR and subsequent Western blot assays were used to determine the expression of miR-339-5p and other related proteins.
RESULTS: We demonstrated that ionizing radiation (IR) exposure impaired lung cancer cell viability, and found that miR-339-5p is a novel IR-inducible miRNA. Overexpression of miR-339-5p enhanced radiosensitivity of A549 and H460 cells by inhibiting cell viability, increasing apoptosis, inducing cell cycle arrest, and suppressing cell proliferation. Further exploration validated that miR-339-5p can target phosphatases of regenerating liver-1 (PRL-1) in lung cancer cells. Restoration of PRL-1 partially reverses the enhanced radiosensitivity of lung cancer cells induced by miR-339-5p.
CONCLUSIONS: Our data support that miR-339-5p has potential therapeutic value by sensitizing lung cancer cells to radiation via targeting of PRL-1.
Keywords: Apoptosis, Lung Neoplasms, MicroRNAs, Radiation Tolerance