Department of Surgery for Organ Function and Biological Regulation, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8602, Japan.
Biochem Biophys Res Commun. 2013 Jan 4;430(1):101-6. doi: 10.1016/j.bbrc.2012.11.005. Epub 2012 Nov 12.
It is now evident that changes in microRNA are involved in cancer progression, but the mechanisms of transcriptional regulation of miRNAs remain unknown. Ski-related novel gene (SnoN/SKIL), a transcription co-factor, acts as a potential key regulator within a complex network of p53 transcriptional repressors. SnoN has pro- and anti-oncogenic functions in the regulation of cell proliferation, senescence, apoptosis, and differentiation. We characterized the roles of SnoN in miRNA transcriptional regulation and its effects on cell proliferation using esophageal squamous cell carcinoma (ESCC) cells. Silencing of SnoN altered a set of miRNA expression profiles in TE-1cells, and the expression levels of miR-720, miR-1274A, and miR-1274B were modulated by SnoN. The expression of these miRNAs resulted in changes to the target protein p63 and a disintegrin and metalloproteinase domain 9 (ADAM9). Furthermore, silencing of SnoN significantly upregulated cell proliferation in TE-1 cells, indicating a potential anti-oncogenic function. These results support our observation that cancer tissues have lower expression levels of SnoN, miR-720, and miR-1274A compared to adjacent normal tissues from ESCC patients. These data demonstrate a novel mechanism of miRNA regulation, leading to changes in cell proliferation.
现在很明显，miRNA 的变化与癌症的进展有关，但 miRNA 的转录调控机制仍不清楚。Ski 相关新型基因（SnoN/SKIL）是一种转录共因子，作为 p53 转录阻遏物复杂网络中的一个潜在关键调节因子。SnoN 在调节细胞增殖、衰老、凋亡和分化方面具有促癌和抑癌作用。我们使用食管鳞状细胞癌（ESCC）细胞，对 SnoN 在 miRNA 转录调控中的作用及其对细胞增殖的影响进行了表征。SnoN 的沉默改变了 TE-1 细胞中一组 miRNA 的表达谱，miR-720、miR-1274A 和 miR-1274B 的表达水平受 SnoN 调节。这些 miRNA 的表达导致靶蛋白 p63 和解整合素金属蛋白酶域 9（ADAM9）的变化。此外，SnoN 的沉默显著上调了 TE-1 细胞的增殖，表明其具有潜在的抑癌功能。这些结果支持了我们的观察结果，即与 ESCC 患者的相邻正常组织相比，癌症组织中 SnoN、miR-720 和 miR-1274A 的表达水平较低。这些数据表明了一种 miRNA 调节的新机制，导致细胞增殖的变化。
