Common genetic variants in miR-1206 (8q24.2) and miR-612 (11q13.3) affect biogenesis of mature miRNA forms.
Common genetic variants in miR-1206 (8q24.2) and miR-612 (11q13.3) affect biogenesis of mature miRNA forms.
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DOI：
10.1371/journal.pone.0047454
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chanock SJ
中科院分区：
文献类型：
--
作者：
Kim HK;Prokunina-Olsson L;Chanock SJ
癌症全基因组关联研究（GWAS）已经确定了许多位于基因组非编码区的常见遗传标记。两个值得注意的例子是多癌症易感区域，8q24.2和11q13.3。由于这些GWAS信号定位于基因贫乏的区域，我们研究了前microRNA（pre-miRNA）转录本内的遗传变异，作为GWAS发现与相关分子表型之间的可能联系。在这两个包含37个miRNAs基因的区域中，我们通过调查公共数据库和进行靶向重测序来探索遗传变异。具体而言，我们研究了8q24.2上miR-1206内的一种常见单核苷酸多态性（SNP）和11q13.3上miR-612内的两种SNP。虽然这些变异体与已知的GWAS信号不相关，但我们证实它们可能对相应miRNA的功能很重要。为了测试这些遗传变体的功能意义，我们将miR-1206和miR-612 pre-miRNA的等位基因形式克隆到表达载体中，并评估成熟miRNA形式的生物发生。miR-612中的两个SNP以细胞类型特异性方式显著影响成熟miR-612的表达;在前列腺癌细胞系中增强，在结肠癌细胞中减少，而在乳腺癌细胞系中没有影响。miR-1206内的SNP也影响成熟miR-1206的表达，但不是以细胞类型特异性的方式。未来的研究应该确定miR-1206和miR-612的靶点，并帮助了解这些miRNA的生物学作用及其在致癌作用中的可能作用。
Cancer genome-wide association studies (GWAS) have identified many common genetic markers located in non-coding regions of the genome. Two notable examples are the multi-cancer susceptibility regions, 8q24.2 and 11q13.3. Since these GWAS signals localize to gene-poor regions, we investigated genetic variants within pre-microRNA (pre-miRNA) transcripts as a possible link between the GWAS findings and the associated molecular phenotypes. Across the two regions, which contain 37 miRNAs genes, we explored genetic variants by surveying public databases and conducting targeted resequencing. Specifically, we investigated one common single nucleotide polymorphism (SNP) within miR-1206 on 8q24.2 and two SNPs within miR-612 on 11q13.3. Though these variants are not correlated with known GWAS signals, we conjectured that they might be important for function of corresponding miRNAs. To test the functional significance of these genetic variants, we cloned both allelic forms of miR-1206 and miR-612 pre-miRNA into expression vectors and assessed biogenesis of mature miRNA-forms. The two SNPs within miR-612 significantly affected expression of mature miR-612 in a cell-type specific manner; enhancement in prostate cancer cell lines, reduction in colon cancer cells, and no effect in breast cancer cell lines. The SNP within miR-1206 also affected expression of mature miR-1206, but not in a cell-type specific manner. Future studies should identify targets of miR-1206 and miR-612 and help understand the biological roles of these miRNAs and their possible role in carcinogenesis.
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影响因子：
30.8
作者：
Kiemeney LA;Thorlacius S;Sulem P;Geller F;Aben KK;Stacey SN;Gudmundsson J;Jakobsdottir M;Bergthorsson JT;Sigurdsson A;Blondal T;Witjes JA;Vermeulen SH;Hulsbergen-van de Kaa CA;Swinkels DW;Ploeg M;Cornel EB;Vergunst H;Thorgeirsson TE;Gudbjartsson D;Gudjonsson SA;Thorleifsson G;Kristinsson KT;Mouy M;Snorradottir S;Placidi D;Campagna M;Arici C;Koppova K;Gurzau E;Rudnai P;Kellen E;Polidoro S;Guarrera S;Sacerdote C;Sanchez M;Saez B;Valdivia G;Ryk C;de Verdier P;Lindblom A;Golka K;Bishop DT;Knowles MA;Nikulasson S;Petursdottir V;Jonsson E;Geirsson G;Kristjansson B;Mayordomo JI;Steineck G;Porru S;Buntinx F;Zeegers MP;Fletcher T;Kumar R;Matullo G;Vineis P;Kiltie AE;Gulcher JR;Thorsteinsdottir U;Kong A;Rafnar T;Stefansson K
通讯作者：
Stefansson K
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
5.2
作者：
Huppi, Konrad;Volfovsky, Natalia;Caplen, Natasha J.
通讯作者：
Caplen, Natasha J.
DOI：
10.1073/pnas.0802682105
发表时间：
2008-05-20
影响因子：
11.1
作者：
Jazdzewski, Krystian;Murray, Elizabeth L.;de la Chapelle, Albert
通讯作者：
de la Chapelle, Albert