microRNA成員之一miR-125b的生物學(xué)功能是多方面的，即可作為一種腫瘤抑制基因,，也可作為促癌基因,。但到目前為止，MIR-125b的促凋亡作用及其機(jī)制仍未被探索,。
近日,，發(fā)表在Oncogene雜志上的一項(xiàng)研究中，過表達(dá)或抑制miR-125b表達(dá)實(shí)驗(yàn)表明miR-125b的表達(dá)不僅誘發(fā)肺和大腸癌等各種細(xì)胞系的轉(zhuǎn)移,，同時也使得癌細(xì)胞對不同凋亡刺激環(huán)境包括營養(yǎng)饑餓下和化療治療更敏感,，誘導(dǎo)癌細(xì)胞凋亡。
此外,，在肝細(xì)胞癌（HCC）組織中miR-125b處于下調(diào)狀態(tài),，其表達(dá)水平與與細(xì)胞凋亡率呈正相關(guān)。隨后研究發(fā)現(xiàn),，miR-125b的直接靶蛋白是Mcl-1,、Bcl-W等凋亡蛋白以及白細(xì)胞介素（IL）-6R。
恢復(fù)miR-125b的表達(dá)不僅直接降低了Mcl-1和Bcl-W的表達(dá),，但也間接地減少激活Mcl-1和Bcl-xL的IL-6信號傳導(dǎo)水平,。與這些結(jié)果一致的是，miR-125b表達(dá)會降低線粒體膜電位和促進(jìn)caspase-3裂解,。
這些數(shù)據(jù)表明miR-125b的表達(dá)可通過抑制抗凋亡蛋白Bcl-2家族促進(jìn)細(xì)胞凋亡,，miR-125b的表達(dá)下調(diào)可能促進(jìn)腫瘤的發(fā)展。這項(xiàng)研究發(fā)現(xiàn)提示miR-125b在細(xì)胞凋亡調(diào)控中的重要性， miR-125b或許可作為抗腫瘤治療的一個有前景的靶標(biāo),。（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.
