1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2].
Nat Genet. 2013 Nov;45(11):1392-8. doi: 10.1038/ng.2771. Epub 2013 Sep 29.
Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority. The molecular basis for this clinical heterogeneity remains incompletely understood. Here we characterize a long noncoding RNA termed SChLAP1 (second chromosome locus associated with prostate-1; also called LINC00913) that is overexpressed in a subset of prostate cancers. SChLAP1 levels independently predict poor outcomes, including metastasis and prostate cancer-specific mortality. In vitro and in vivo gain-of-function and loss-of-function experiments indicate that SChLAP1 is critical for cancer cell invasiveness and metastasis. Mechanistically, SChLAP1 antagonizes the genome-wide localization and regulatory functions of the SWI/SNF chromatin-modifying complex. These results suggest that SChLAP1 contributes to the development of lethal cancer at least in part by antagonizing the tumor-suppressive functions of the SWI/SNF complex.
前列腺癌在多数患者中呈惰性生长，但在少数患者中具有侵袭性。这种临床异质性的分子基础仍不完全清楚。在这里，我们描述了一种长非编码 RNA，称为 SChLAP1（与前列腺相关的第二号染色体位点 1；也称为 LINC00913），其在一部分前列腺癌中过度表达。SChLAP1 水平独立预测不良预后，包括转移和前列腺癌特异性死亡率。体外和体内功能获得和功能丧失实验表明，SChLAP1 对于癌细胞的侵袭和转移至关重要。从机制上讲，SChLAP1 拮抗 SWI/SNF 染色质修饰复合物的全基因组定位和调节功能。这些结果表明，SChLAP1 通过拮抗 SWI/SNF 复合物的肿瘤抑制功能，至少在一定程度上促进了致命性癌症的发展。
