c-Myc 是个转录因子在它的转基因小鼠中过表c-Myc 会导致乳腺癌。为了检测确切的mirRNA调节了 c-Myc 诱导的小鼠乳腺癌生成作用, 我们在MMTV-c-myc 转基因小鼠诱导的乳腺癌中进行mirRNA表达谱,结果发现与野生型泌乳乳腺相比有50个 mirRNA表达上升和 59个 mirRNA表达下降。由于具有相同的染色体定位和可能有相同的原始RNA转录本，其中的24个mirRNA 可以归为8 类。表达上升的 mir-20a, mir-20b 及mir-9 和表达下降的mir-222 一样都经过 RT-PCR, real-time RT-PCR, 和 cDNA 测序所证实。此外，我们意外的鉴定了一个新的非编码RNA，它的表达水平在MMTV-c-myc 转基因小鼠的增值乳腺中表达下调，但是在乳腺癌中没有检出。将该RNA测序发现它由小鼠19号染色体的一段区域转录，该区域包含有非蛋白编码基因：肺癌转移伴随因子转录本-1 (Malat-1) 。这些结果提示：一些确定的mirRNA和19号染色体衍生的非编码RNA调节了c-myc诱导的小鼠乳腺癌生成作用。

1: Breast Cancer Res Treat. 2008 Sep 7. [Epub ahead of print]

Sun Y, Wu J, Wu SH, Thakur A, Bollig A, Huang Y, Joshua Liao D.

Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.

c-Myc is a transcription factor overexpression of which induces mammary cancer in transgenic mice. To explore whether certain microRNAs (mirRNA) mediate c-Myc induced mammary carcinogenesis, we studied mirRNA expression profile in mammary tumors developed from MMTV-c-myc transgenic mice, and found 50 and 59 mirRNAs showing increased and decreased expression, respectively, compared with lactating mammary glands of wild type mice. Twenty-four of these mirRNAs could be grouped into eight clusters because they had the same chromosomal localizations and might be processed from the same primary RNA transcripts. The increased expression of mir-20a, mir-20b, and mir-9 as well as decreased expression of mir-222 were verified by RT-PCR, real-time RT-PCR, and cDNA sequencing. Moreover, we fortuitously identified a novel non-coding RNA, the level of which was decreased in proliferating mammary glands of MMTV-c-myc mice was further decreased to undetectable level in the mammary tumors. Sequencing of this novel RNA revealed that it was transcribed from a region of mouse chromosome 19 that harbored the metastasis associated lung adenocarcinoma transcript-1 (Malat-1), a non-protein-coding gene. These results suggest that certain mirRNAs and the chromosome 19 derived non-coding RNAs may mediate c-myc induced mammary carcinogenesis.

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