Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Cancer Res. 2019 Jul 15;79(14):3542-3556. doi: 10.1158/0008-5472.CAN-18-2900. Epub 2019 Mar 11.
Accumulating evidence suggests that long noncoding RNA (lncRNA) plays important regulatory roles in cancer biology. However, the involvement of lncRNA in colorectal carcinoma progression remains largely unknown, especially in colorectal carcinoma metastasis. In this study, we investigated the changes in lncRNA expression in colorectal carcinoma and identified a new lncRNA, the antisense transcript of SATB2 (), as a key regulator of colorectal carcinoma progression. was frequently downregulated in colorectal carcinoma cells and tissues, and patients whose tumors expressed at low levels had a shorter overall survival and poorer prognosis. Downregulation of significantly promoted cell proliferation, migration, and invasion and , demonstrating that it acts as a tumor suppressor in colorectal carcinoma. suppressed colorectal carcinoma progression by serving as a scaffold to recruit p300, whose acetylation of H3K27 and H3K9 at the promoter upregulated expression of , a suppressor of colorectal carcinoma growth and metastasis. SATB2 subsequently recruited HDAC1 to the promoter, repressing transcription and inhibiting epithelial-to-mesenchymal transition. Taken together, these data reveal as a novel regulator of the SATB2-Snail axis whose loss facilitates progression of colorectal carcinoma. SIGNIFICANCE: These data show that the lncRNA mediates epigenetic regulation of and expression to suppress colorectal cancer progression..
越来越多的证据表明，长非编码 RNA（lncRNA）在癌症生物学中发挥着重要的调控作用。然而，lncRNA 参与结直肠癌进展的机制在很大程度上尚不清楚，特别是在结直肠癌转移中。在本研究中，我们研究了 lncRNA 在结直肠癌中的表达变化，发现了一种新的 lncRNA，SATB2 的反义转录本（），是结直肠癌进展的关键调节因子。在结直肠癌细胞和组织中，表达下调，肿瘤表达水平低的患者总生存期和预后较差。下调显著促进了细胞增殖、迁移和侵袭，表明其在结直肠癌中起肿瘤抑制因子的作用。通过作为募集 p300 的支架，抑制结直肠癌的进展，p300 在 启动子上乙酰化 H3K27 和 H3K9，上调 的表达，抑制结直肠癌的生长和转移。SATB2 随后将 HDAC1 募集到 启动子上，抑制 转录，抑制上皮间质转化。总之，这些数据揭示了 作为 SATB2-Snail 轴的新型调节剂，其缺失促进了结直肠癌的进展。意义：这些数据表明，lncRNA 通过介导 的表观遗传调控来抑制结直肠癌的进展。
