microRNA成员之一miR-125b的生物学功能是多方面的，即可作为一种肿瘤抑制基因，也可作为促癌基因。但到目前为止，MIR-125b的促凋亡作用及其机制仍未被探索。
近日，发表在Oncogene杂志上的一项研究中，过表达或抑制miR-125b表达实验表明miR-125b的表达不仅诱发肺和大肠癌等各种细胞系的转移，同时也使得癌细胞对不同凋亡刺激环境包括营养饥饿下和化疗治疗更敏感，诱导癌细胞凋亡。
此外，在肝细胞癌（HCC）组织中miR-125b处于下调状态，其表达水平与与细胞凋亡率呈正相关。随后研究发现，miR-125b的直接靶蛋白是Mcl-1、Bcl-W等凋亡蛋白以及白细胞介素（IL）-6R。
恢复miR-125b的表达不仅直接降低了Mcl-1和Bcl-W的表达，但也间接地减少激活Mcl-1和Bcl-xL的IL-6信号传导水平。与这些结果一致的是，miR-125b表达会降低线粒体膜电位和促进caspase-3裂解。
这些数据表明miR-125b的表达可通过抑制抗凋亡蛋白Bcl-2家族促进细胞凋亡，miR-125b的表达下调可能促进肿瘤的发展。这项研究发现提示miR-125b在细胞凋亡调控中的重要性， miR-125b或许可作为抗肿瘤治疗的一个有前景的靶标。（生物谷：Bioon.com）
doi:10.1038/onc.2012.318
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MicroRNA-125b promotes apoptosis by regulating the expression of Mcl-1, Bcl-w and IL-6R.
Gong J, Zhang JP, Li B, Zeng C, You K, Chen MX, Yuan Y, Zhuang SM.
The microRNA miR-125b is multi-faceted, with the ability to function as a tumor suppressor or an oncogene, depending on the cellular context. To date, the pro-apoptotic role of miR-125b and its underlying mechanisms are unexplored. In this study, both gain- and loss-of-function experiments revealed that miR-125b expression not only induced spontaneous apoptosis in various cell lines derived from the liver, lung and colorectal cancers, but also sensitized cancer cells to diverse apoptotic stimuli, including nutrient starvation and chemotherapeutic treatment. Furthermore, downregulation of miR-125b was a frequent event in hepatocellular carcinoma (HCC) tissues, and the miR-125b level was positively associated with the rate of apoptosis in HCC tissues. Subsequent investigations identified Mcl-1, Bcl-w and interleukin (IL)-6R as direct targets of miR-125b. Restoration of miR-125b expression not only diminished the expression of Mcl-1 and Bcl-w directly but also indirectly reduced the Mcl-1 and Bcl-xL levels by attenuating IL-6/signal transducer and activator of transcription 3 signaling. Consistent with these findings, introduction of miR-125b reduced the mitochondrial membrane potential and promoted the cleavage of pro-caspase-3. These data indicate that miR-125b may promote apoptosis by suppressing the anti-apoptotic molecules of the Bcl-2 family and miR-125b downregulation may facilitate tumor development by conferring upon cells the capability to survive under conditions of nutrient deprivation and chemotherapeutic treatment. Our findings highlight the importance of miR-125b in the regulation of apoptosis and suggest miR-125b as an attractive target for anti-cancer therapy.
