Tribollet Violaine, Barenton Bruno, Kroiss Auriane, Vincent Séverine, Zhang Ling, Forcet Christelle, Cerutti Catherine, Périan Séverine, Allioli Nathalie, Samarut Jacques, Vanacker Jean-Marc
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, Lyon, France.
Institut des Sciences Pharmaceutiques et Biologiques, Faculté de Pharmacie, Université de Lyon, Lyon, France.
PLoS One. 2016 May 26;11(5):e0156445. doi: 10.1371/journal.pone.0156445. eCollection 2016.
MicroRNA-135a (miR-135a) down-modulates parameters of cancer progression and its expression is decreased in metastatic breast cancers (as compared to non-metastatic tumors) as well as in prostate tumors relative to normal tissue. These expression and activity patterns are opposite to those of the Estrogen-Related Receptor α (ERRα), an orphan member of the nuclear receptor family. Indeed high expression of ERRα correlates with poor prognosis in breast and prostate cancers, and the receptor promotes various traits of cancer aggressiveness including cell invasion. Here we show that miR-135a down-regulates the expression of ERRα through specific sequences of its 3'UTR. As a consequence miR-135a also reduces the expression of downstream targets of ERRα. miR-135a also decreases cell invasive potential in an ERRα-dependent manner. Our results suggest that the decreased expression of miR-135a in metastatic tumors leads to elevated ERRα expression, resulting in increased cell invasion capacities.
微小RNA-135a（miR-135a）下调癌症进展参数，其在转移性乳腺癌（与非转移性肿瘤相比）以及前列腺肿瘤相对于正常组织中的表达降低。这些表达和活性模式与核受体家族的孤儿成员雌激素相关受体α（ERRα）相反。事实上，ERRα的高表达与乳腺癌和前列腺癌的不良预后相关，并且该受体促进包括细胞侵袭在内的各种癌症侵袭性特征。在这里，我们表明miR-135a通过其3'非翻译区的特定序列下调ERRα的表达。因此，miR-135a也降低了ERRα下游靶标的表达。miR-135a还以ERRα依赖的方式降低细胞侵袭潜力。我们的结果表明，转移性肿瘤中miR-135a表达的降低导致ERRα表达升高，从而导致细胞侵袭能力增加。
