miR-139 通过 Beclin-1 和 mTOR 信号蛋白调节前列腺癌细胞自噬。
Mir-139 Regulates Autophagy in Prostate Cancer Cells Through Beclin-1 and mTOR Signaling Proteins.
机构信息
Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Platform Biological Sciences, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
出版信息
Anticancer Res. 2020 Dec;40(12):6649-6663. doi: 10.21873/anticanres.14689. Epub 2020 Dec 7.
BACKGROUND/AIM: We previously identified a panel of five miRNAs (including miR-139) associated with biochemical recurrence and metastasis in prostate cancer patients.
MATERIALS AND METHODS
We examined miR-139 transfected PC3, DU145 and LNCaP cells by morphology as well as by cell-based assays, confocal microscopy and immunoblotting.
RESULTS
We found that treatment of prostate cancer cells with miR-139 resulted in phenotypic changes characteristic of autophagic cells. MiR-139 increased the autophagy-related conversion of the microtubule-associated protein light chain 3 (LC3-I to LC3-II) that was specifically inhibited by the miR-139 antagomir. The upregulation of LC3 II was further confirmed by confocal microscopy. miR-139 regulated activation of both mTOR and Beclin1 the two important autophagy-related molecules. We found that upon miR-139 treatment, the cargo adaptor protein p62 which is degraded during autophagy, accumulates.
CONCLUSION
These results suggest that miR-139 is inducing autophagic flux blockade leading to apoptosis in prostate cancer cells through the mTOR and Beclin-1 proteins.
背景/目的：我们之前确定了一组与前列腺癌患者生化复发和转移相关的五个 miRNAs（包括 miR-139）。
材料和方法
我们通过形态学以及细胞基础检测、共聚焦显微镜和免疫印迹法检查了转染 miR-139 的 PC3、DU145 和 LNCaP 细胞。
结果
我们发现，miR-139 处理前列腺癌细胞导致具有自噬细胞特征的表型变化。miR-139 增加了微管相关蛋白轻链 3（LC3-I 向 LC3-II）的自噬相关转化，该转化被 miR-139 反义寡核苷酸特异性抑制。共聚焦显微镜进一步证实了 LC3 II 的上调。miR-139 调节了两个重要的自噬相关分子 mTOR 和 Beclin1 的激活。我们发现，在用 miR-139 处理后，货物衔接蛋白 p62 在自噬过程中降解，其积累。
结论
这些结果表明，miR-139 通过 mTOR 和 Beclin-1 蛋白诱导前列腺癌细胞中自噬通量阻断，导致细胞凋亡。
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