Bilbao-Aldaiturriaga Nerea, Gutierrez-Camino Angela, Martin-Guerrero Idoia, Pombar-Gomez Maria, Zalacain-Diez Marta, Patiño-Garcia Ana, Lopez-Lopez Elixabet, Garcia-Orad Africa
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Odontology, University of the Basque Country (UPV/EHU), Leioa, Spain.
Pediatr Blood Cancer. 2015 May;62(5):766-9. doi: 10.1002/pbc.25416. Epub 2015 Feb 7.
The possible associations between genetic variants and osteosarcoma risk have been analyzed without conclusive results. Those studies were focused mainly on genes of biologically plausible pathways. However, recently, another pathway has acquired relevance in cellular transformation and tumorigenesis, the microRNA (miRNA) processing pathway. Dysregulation of the expression levels of genes in this pathway has been described in cancer. Consequently, single nucleotide polymorphisms (SNPs) in genes that codify for proteins involved in the miRNA processing pathway may affect miRNAs, and therefore their target genes, which might be associated with cancer development and progression. The aim of this study was to evaluate whether SNPs in miRNA processing genes confer predisposition to osteosarcoma.
We analyzed 72 SNPs in 21 miRNA processing genes in a total of 99 osteosarcoma patients and 387 controls.
A total of three SNPs were associated with osteosarcoma susceptibility. Interestingly, these SNPs were located in miRNA processing genes (CNOT1, CNOT4 and SND1) which are part of the RISC complex. Among them, the association of rs11866002 in CNOT1 was nearly significant after Bonferroni correction.
This study suggests that SNPs in RISC complex genes may be involved in osteosarcoma susceptibility, especially rs11866002 in CNOT1.
已经分析了基因变异与骨肉瘤风险之间可能存在的关联，但结果尚无定论。这些研究主要集中在具有生物学合理性的信号通路相关基因上。然而，最近，另一条信号通路在细胞转化和肿瘤发生过程中变得愈发重要，即微小RNA（miRNA）加工信号通路。在癌症中已发现该信号通路中基因的表达水平失调。因此，编码参与miRNA加工信号通路蛋白质的基因中的单核苷酸多态性（SNP）可能会影响miRNA，进而影响其靶基因，这可能与癌症的发生和发展相关。本研究的目的是评估miRNA加工基因中的SNP是否会使人易患骨肉瘤。
我们分析了总共99例骨肉瘤患者和387例对照中21个miRNA加工基因中的72个SNP。
共有三个SNP与骨肉瘤易感性相关。有趣的是，这些SNP位于作为RNA诱导沉默复合体（RISC）一部分的miRNA加工基因（CNOT1、CNOT4和SND1）中。其中，CNOT1基因中的rs11866002在经过Bonferroni校正后关联接近显著。
本研究表明，RISC复合体基因中的SNP可能与骨肉瘤易感性有关，尤其是CNOT1基因中的rs11866002。
