MicroRNA 133B targets pro-survival molecules MCL-1 and BCL2L2 in lung cancer.

Lung cancer is the most frequent cause of cancer-related death in this country for men and women. MicroRNAs (miRNAs) are a family of small non-coding RNAs (approximately 21–25 nt long) capable of targeting genes for either degradation of mRNA or inhibition of translation. We identified aberrant expression of 41 miRNAs in lung tumor versus uninvolved tissue. MiR-133B had the lowest expression of miRNA in lung tumor tissue (28 fold reduction) compared to adjacent uninvolved tissue. We identified two members of the BCL-2 family of pro-survival molecules (MCL-1 and BCL2L2 (BCLw)) as predicted targets of miR-133B. Selective over-expression of miR-133B in adenocarcinoma (H2009) cell lines resulted in reduced expression of both MCL-1 and BCL2L2. We then confirmed that miR-133B directly targets the 3’UTRs of both MCL-1 and BCL2L2. Lastly, over-expression of miR-133B induced apoptosis following gemcitabine exposure in these tumor cells. To our knowledge, this represents the first observation of decreased expression of miR-133B in lung cancer and that it functionally targets members of the BCL-2 family.

在这个国家，肺癌是男性和女性癌症相关死亡的最常见原因。微小核糖核酸（miRNAs）是一类小分子非编码RNA（长度约为21 - 25个核苷酸），能够针对基因进行信使核糖核酸（mRNA）降解或翻译抑制。我们发现与未受累组织相比，在肺肿瘤中有41种miRNAs表达异常。与相邻的未受累组织相比，miR - 133B在肺肿瘤组织中的表达量最低（降低了28倍）。我们确定了促存活分子BCL - 2家族的两个成员（MCL - 1和BCL2L2（BCLw））是miR - 133B的预测靶点。在腺癌（H2009）细胞系中选择性过表达miR - 133B导致MCL - 1和BCL2L2的表达均降低。然后我们证实miR - 133B直接靶向MCL - 1和BCL2L2的3’非翻译区。最后，在这些肿瘤细胞中，miR - 133B的过表达在吉西他滨暴露后诱导了细胞凋亡。据我们所知，这是首次观察到miR - 133B在肺癌中表达降低，并且它在功能上靶向BCL - 2家族成员。