微小核糖酸-107藉由抑制顆粒體的表現而增進PC-3前列腺癌細胞的放射敏感性

羅華成1, 2、許家豪2、賴亮全3、蔡孟勳4、莊曜宇2

1國防醫學院三軍總醫院松山分院泌尿外科;2國立台灣大學生醫電子與資訊學研究所,3生理學研究所,4生物科技研究所。

MicroRNA-107 Enhances Radiosensitivity by Suppressing Granulin in PC-3 Prostate Cancer Cells

Hua-Cheng Lo1,2, Jia-Hao Hsu2, Liang-Chuan Lai3, Mong-Hsun Tsai4, Eric Y. Chuang2

1Division of Urology, Tri-Service General Hospital Song-Shan Branch, National Defense Medical Center, Taipei, Taiwan; 2Graduate Institute of Biomedical Electronics and Bioinformatics, 3Graduate Institute of Physiology, College of Medicine, 4Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.

 

Purpose:

Prostate cancer (PCa) is the second leading cause of cancer-related mortality worldwide. Radiotherapy is often applied for the treatment of PCa, but radioresistance is a challenge in some PCa patients. MicroRNAs (miRNAs) have been reported to be involved in the DNA damage response induced by ionizing radiation (IR) and recent studies have reported miRNA-mediated radiosensitivity.

Materials and Methods:

The human prostate cancer cell lines, PC-3, LNCaP and DU145 were selected and compared after exposure to irradiations delivered by a 137Cs irradiator. PC-3 cells in exponential growth were irradiated at room temperature, and non-irradiated culture cells were handled in parallel with the irradiated samples. Cellular infection and transfection were applied to achieve microRNA-107 (miR-107) and granulin (GRN) overexpression. GRN knockdown were achieved by viral transfection of plasmid containing shRGN. The analysis of changes in phenotype were conducted by using qRT-PCR quantification, clonogenic assay, western blotting, cell proliferation assay, flow cytometry analysis of the cell cycle, annexin V analysis.

Results:

We found that miR-107 enhanced radiosensitivity by regulating GRN in prostate cancer (PC-3) cells. MiR-107 was downregulated and GRN was upregulated in response to IR in PC-3 cells. Overexpression of miR-107 and knockdown of GRN promoted the sensitivity of PC3 cells to IR. By rescue experiments of GRN, we revealed that radiosensitivity enhanced by miR-107 can be attenuated by GRN overexpression in PC3 cells. Furthermore, we showed that miR-107 enhanced radiation-induced G1/S phase arrest and G2/M phase transit, and identify delayed apoptosis by suppressing p21 and phosphorylation of CHK2.

Conclusion:

Collectively, these results highlight an unrecognized mechanism of miR-107-mediated GRN regulation in response to IR and may advance therapeutic strategies for the treatment of prostate cancer.

 

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    台灣泌尿科醫學會
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    2021-05-20 15:25:33
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    2021-05-20 15:38:51
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