Cordeiro Anna, Navarro Alfons, Gaya Anna, Díaz-Beyá Marina, Gonzalez-Farré Blanca, Castellano Joan Josep, Fuster Dolors, Martínez Carmen, Martínez Antonio, Monzó Mariano
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
Hematology Department, Hospital Clinic Barcelona, IDIBAPS, Barcelona, Spain.
Oncotarget. 2016 Jul 19;7(29):46002-46013. doi: 10.18632/oncotarget.10015.
PiwiRNAs, small non-coding RNAs processed by Piwi proteins, are involved in maintaining genome stability in germline cells. Recently, piwiRNA expression has been identified in some tumors. We have examined the potential reactivation of the Piwi/piwiRNA pathway in classical Hodgkin lymphoma (cHL). We found that Piwi proteins and three selected piwiRNAs, including piR-651, were expressed in cHL patients and cell lines, indicating that the Piwi/piwiRNA pathway is active in cHL. Interestingly, low levels of piR-651 were associated with lack of complete response to first-line treatment, as well as shorter disease-free and overall survival in a cohort of 94 cHL patients. At diagnosis, piR-651 was underexpressed in cHL serum samples compared to healthy controls, while after complete remission, piR-651 levels increased to levels similar to healthy controls. This is the first evidence that piwiRNAs are active in tumor and serum samples and impact prognosis in cHL.
PiwiRNAs是由Piwi蛋白加工而成的小型非编码RNA,参与维持生殖细胞中的基因组稳定性。最近,在一些肿瘤中已鉴定出piwiRNA表达。我们研究了经典型霍奇金淋巴瘤(cHL)中Piwi/piwiRNA途径的潜在重新激活。我们发现Piwi蛋白和三种选定的piwiRNAs,包括piR-651,在cHL患者和细胞系中表达,表明Piwi/piwiRNA途径在cHL中是活跃的。有趣的是,在一组94例cHL患者中,低水平的piR-651与一线治疗缺乏完全缓解以及无病生存期和总生存期较短相关。在诊断时,与健康对照相比,cHL血清样本中piR-651表达不足,而在完全缓解后,piR-651水平升高至与健康对照相似的水平。这是piwiRNAs在肿瘤和血清样本中活跃并影响cHL预后的首个证据。