MYH9与长链非编码RNA基因PTCSC2结合，并在9q22甲状腺癌风险位点调控FOXE1。
MYH9 binds to lncRNA gene PTCSC2 and regulates FOXE1 in the 9q22 thyroid cancer risk locus.
作者信息
Wang Yanqiang, He Huiling, Li Wei, Phay John, Shen Rulong, Yu Lianbo, Hancioglu Baris, de la Chapelle Albert
机构信息
Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
Department of Cancer Biology and Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
出版信息
Proc Natl Acad Sci U S A. 2017 Jan 17;114(3):474-479. doi: 10.1073/pnas.1619917114. Epub 2017 Jan 3.
A locus on chromosome 9q22 harbors a SNP (rs965513) firmly associated with risk of papillary thyroid carcinoma (PTC). The locus also comprises the forkhead box E1 (FOXE1) gene, which is implicated in thyroid development, and a long noncoding RNA (lncRNA) gene, papillary thyroid cancer susceptibility candidate 2 (PTCSC2). How these might interact is not known. Here we report that PTCSC2 binds myosin-9 (MYH9). In a bidirectional promoter shared by FOXE1 and PTCSC2, MYH9 inhibits the promoter activity in both directions. This inhibition can be reversed by PTCSC2, which acts as a suppressor. RNA knockdown of FOXE1 in primary thyroid cells profoundly interferes with the p53 pathway. We propose that the interaction between the lncRNA, its binding protein MYH9, and the coding gene FOXE1 underlies the predisposition to PTC triggered by rs965513.
9号染色体q22区域的一个位点含有一个与甲状腺乳头状癌（PTC）风险密切相关的单核苷酸多态性（SNP，rs965513）。该位点还包含与甲状腺发育相关的叉头框E1（FOXE1）基因以及一个长链非编码RNA（lncRNA）基因——甲状腺乳头状癌易感性候选基因2（PTCSC2）。目前尚不清楚它们之间是如何相互作用的。在此，我们报告PTCSC2与肌球蛋白9（MYH9）结合。在FOXE1和PTCSC2共享的双向启动子中，MYH9会抑制两个方向的启动子活性。这种抑制作用可被作为抑制因子的PTCSC2逆转。在原代甲状腺细胞中敲低FOXE1的RNA会严重干扰p53信号通路。我们认为，lncRNA、其结合蛋白MYH9和编码基因FOXE1之间的相互作用是rs965513引发PTC易感性的基础。
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