PDF(Pubmed)
Abstract：
We previously showed that MYC promoted Burkitt lymphoma (BL) growth by inhibiting the tumor suppressor miR-150, resulting in release of miR-150 targets MYB and ZDHHC11. The ZDHHC11 gene encodes three different transcripts including a mRNA (pcZDHHC11), a linear long non-coding RNA (lncZDHHC11) and a circular RNA (circZDHHC11). All transcripts contain the same region with 18 miR-150 binding sites. Here we studied the relevance of circZDHHC11, including this miR-150 binding site region, for growth of BL cells. CircZDHHC11 was mainly present in the cytoplasmic fraction in BL cells and its localization was not altered upon miR-150 overexpression. Knockdown of circZDHHC11 caused a strong inhibition of BL growth without affecting the expression levels of MYC, MYB, miR-150 and other genes. Overexpression of circZDHHC11 neither affected cell growth, nor rescued the phenotype induced by miR-150 overexpression. Genomic deletion of the miR-150 binding site region did not affect growth, nor did it change the effect of circZDHHC11 knockdown. This indicated that the miR-150 binding site region is dispensable for the growth promoting role of circZDHHC11. To conclude, our results show that circZDHHC11 is a crucial factor supporting BL cell growth independent of its ability to sponge miR-150.
摘要：
我们先前表明MYC通过抑制肿瘤抑制因子miR-150促进伯基特淋巴瘤（BL）的生长，导致miR-150靶标MYB和ZDHHC11的释放。ZDHHC11基因编码三种不同的转录本，包括mRNA（pcZDHHC11），线性长非编码RNA(lncZDHHC11)和环状RNA(circZDHHC11)。所有转录物含有具有18个miR-150结合位点的相同区域。在这里，我们研究了circZDHHC11的相关性，包括这个miR-150结合位点区域，用于BL细胞的生长。CircZDHHC11主要存在于BL细胞的细胞质部分中，其定位在miR-150过表达后没有改变。敲除circZDHHC11引起对BL生长的强烈抑制，而不影响MYC的表达水平，MYB,miR-150等基因。circZDHHC11的过表达既不影响细胞生长，也拯救了miR-150过表达诱导的表型。miR-150结合位点区域的基因组缺失不影响生长，也没有改变circZDHHC11敲低的效果。这表明miR-150结合位点区域对于circZDHHC11的生长促进作用是不必要的。最后，我们的结果表明circZDHHC11是支持BL细胞生长的关键因素，而与其海绵miR-150的能力无关。
