Division in Anatomy and Developmental Biology, Department of Oral Biology, Brain Korea 21 Project, Oral Science Research Center, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemoon-Gu, Seoul, 120-752, Korea.
Cell Tissue Res. 2013 Sep;353(3):425-33. doi: 10.1007/s00441-013-1653-3. Epub 2013 Jun 4.
MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translational repression or RNA degradation. The aberrant expression of miRNAs might be involved in human diseases, including cancer. The expression of miR-206 in estrogen receptor alpha (ER-α)-positive human breast cancer tissues is well known. However, the expression and regulation of miR-206 in the developing mammary gland has not yet been studied. To understand the effects of miR-206 on mammary gland development, we have profiled gene expression in scramble-transfected and miR-206-overexpressing developing mammary buds. The genes that are potentially regulated by miR-206 in the mammary epithelium and/or mesenchyme, such as Tachykinin1 and Gata3, are known to be breast cancer markers. The expression of Wnt, which is involved in gland positioning, and of the transcription factors Tbx3 and Lef1, which are essential for mammary gland development, changes after miR-206 overexpression. Using a mammary bud in vitro culture system, we have demonstrated that miR-206 acts downstream of ER-α during mammary gland growth. Thus, miR-206 might be a novel candidate for morphogenesis during the initiation of mammary gland formation and the regulation of genes related to mammary gland development and breast cancer.
微小 RNA(miRNA)是一类小的非编码 RNA,通过靶向 mRNAs 并触发翻译抑制或 RNA 降解来控制基因表达。miRNA 的异常表达可能与人类疾病有关,包括癌症。miR-206 在雌激素受体 alpha(ER-α)阳性的人类乳腺癌组织中的表达是众所周知的。然而,miR-206 在乳腺发育中的表达和调节尚未得到研究。为了了解 miR-206 对乳腺发育的影响,我们对转染 scramble 和 miR-206 过表达的发育中的乳腺芽进行了基因表达谱分析。miR-206 在乳腺上皮和/或间充质中潜在调节的基因,如 Tachykinin1 和 Gata3,是已知的乳腺癌标志物。Wnt 的表达发生变化,其参与腺体定位,转录因子 Tbx3 和 Lef1 的表达对于乳腺发育是必不可少的,这些变化发生在 miR-206 过表达之后。使用乳腺芽体外培养系统,我们已经证明 miR-206 在乳腺生长过程中 ER-α 的下游发挥作用。因此,miR-206 可能是乳腺形成起始时形态发生和与乳腺发育和乳腺癌相关的基因调节的一个新的候选者。