Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, People's Republic of China.
IUBMB Life. 2020 Feb;72(2):237-246. doi: 10.1002/iub.2158. Epub 2019 Sep 3.
Accumulating evidence suggests that long noncoding RNA (lncRNA) plays a fundamental role in cancer progression. However, its biological function in papillary thyroid carcinoma (PTC) has not been fully elucidated. Here, we deciphered the essential role of lncRNA SAMMSON in PTC. SAMMSON was identified to be notably upregulated in PTC cells, tissues, and plasma, and could be used as an effective diagnostic and prognostic biomarker for PTC patients. Knockdown of SAMMSON significantly inhibited PTC cell proliferation and invasion in vitro as well as tumorigenicity and metastasis in vivo. Mechanistically, SAMMSON was transcriptionally elevated by oncogenic Sp1, in turn, upregulated SAMMSON was capable of acting as a scaffold to recruit p300 to increase H3K9ac and H3K27ac levels on Sp1 promoter region, leading to transcriptional activation of Sp1, thereby facilitating PTC progression. Taken together, our data demonstrate that SAMMSON is an oncogenic lncRNA and unveil the crucial role of SAMMSON/Sp1 positive feedback loop in tumorigenesis and aggressiveness of PTC.
越来越多的证据表明，长非编码 RNA（lncRNA）在癌症进展中起着至关重要的作用。然而，其在甲状腺乳头状癌（PTC）中的生物学功能尚未完全阐明。在这里，我们揭示了 lncRNA SAMMSON 在 PTC 中的重要作用。SAMMSON 在 PTC 细胞、组织和血浆中明显上调，可作为 PTC 患者有效的诊断和预后生物标志物。SAMMSON 的敲低显著抑制了 PTC 细胞在体外的增殖和侵袭，以及体内的致瘤性和转移。从机制上讲，致癌 Sp1 转录上调 SAMMSON，反过来，上调的 SAMMSON 能够作为支架招募 p300，增加 Sp1 启动子区域上的 H3K9ac 和 H3K27ac 水平，导致 Sp1 的转录激活，从而促进 PTC 的进展。总之，我们的数据表明 SAMMSON 是一种致癌 lncRNA，并揭示了 SAMMSON/Sp1 正反馈环在 PTC 发生和侵袭性中的关键作用。
