MicroRNA sequence polymorphisms and the risk of different types of cancer

Hu, Ye; Yu, Chuangqi; Wang, Jilin; Guan, Jian; Chen, Haoyan; Fang, Jing‐Yuan

doi:10.1038/srep03648

Cited by 61 publications

(62 citation statements)

References 56 publications

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“…Mutations of the 3p arm of miR-142 (both-arm type) were recently found in acute myeloid leukemia (AML) 39 , and variation of the 3p arm of immune-related miR-146a has been reported to be associated with the risks of acquiring various types of cancer 40,41 (schematic of mutations in Fig. 8a).…”

Section: Asymmetry Alteration By Cancer-related Mirna Variationsmentioning

confidence: 99%

Small-RNA asymmetry is directly driven by mammalian Argonautes

Suzuki

Katsura

Yasuda

et al. 2015

Nat Struct Mol Biol

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Asymmetric selection of single-stranded guide RNAs from double-stranded RNA precursors is crucial in RNA silencing-mediated gene regulation. However, the precise mechanisms of small-RNA asymmetry are unclear, especially because asymmetric selection can still occur when the putative asymmetry sensors Drosophila R2D2 and mammalian Dicer are depleted. Here we report a direct contribution of mammalian Argonaute 2 (Ago2) to microRNA (miRNA) asymmetry. Ago2 selects strands with 5'-uridine or 5'-adenosine and thermodynamically unstable 5' ends in parallel through its two sensor regions, which contact the 5' nucleobases and 5'-phosphates of prospective guide strands. Hence, miRNA asymmetry shows superposed patterns reflecting 5'-end nucleotide identity ('digital' pattern) and thermodynamic stability ('analog' pattern). Furthermore, we demonstrate that cancer-associated miRNA variations reprogram asymmetric selection. Finally, our study presents a model of this universal principle, to aid in comprehensive understanding of miRNA function and development of new RNA-silencing therapies in precision medicine.

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Section: Asymmetry Alteration By Cancer-related Mirna Variationsmentioning

confidence: 99%

Small-RNA asymmetry is directly driven by mammalian Argonautes

Suzuki

Katsura

Yasuda

et al. 2015

Nat Struct Mol Biol

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“…MicroRNAs (miRNAs/miRs) are non-coding RNAs with complex biological functions that regulate the expression of numerous proteins through direct binding to the 3'-untranslated region of target genes (15,16). It has been well-documented that miRNAs are involved in a wide range of ovarian cancer tumorigenic processes, including malignant transformation, differentiation, proliferation and apoptosis (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer

Song

Zhao

et al. 2015

Oncology Letters

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Abstract. Polymorphisms in microRNA (miR) genes and their target sites are a distinct classification of variation in the human genome, which are rapidly being identified and investigated in human cancer. A polymorphism in the miR-196a-2 locus has demonstrated significant associations with various types of cancer, including lung, breast, esophageal and gastric tumors. However, miR-196a-2 has not been fully explored in ovarian cancer, which shares similar biological characteristics with other types of cancer. Therefore, the present study aimed to elucidate the association between a single nucleotide polymorphism (SNP) in the mature sequence of miR-196a-2 (rs11614913, T/C) and the clinical features of 479 Chinese patients with epithelial ovarian cancer (EOC). In addition, the biological significance of this polymorphism was investigated in the OVCAR3 ovarian cancer cell line. Risk association was evaluated in 479 cases of EOC patients and 431 controls. SNPs were analyzed by using polymerase chain reaction based restriction fragment length polymorphism assay. miR-196a expression was evaluated with reverse transcription polymerase chain reaction. The influence of miR-196a-2 rs11614913 T/C on EOC cell migration and invasion ability was further investigated in vitro. The results revealed significant differences in the homozygous CC genotype distribution in patients with EOC (n=479), compared with that of the control subjects (n=431; P=0.026). Analysis of the association between genotype and the risk of EOC revealed that individuals who carried the homozygous CC genotype were 1.34-fold more susceptible to EOC, compared with those carrying the wild-type TT and heterozygous CT genotypes [odds ratio, 1.34; 95% confidence interval, 1.04-2.17; P= 0.023].In addition, the role of this polymorphism in the production of mature miR-196a was investigated. Significantly enhanced production of mature miR-196a was revealed in the C-allelic compared with that of the T-allelic miR-196a-2 precursor (P<0.05). Further examination indicated that miR-196a significantly promoted cell migration and invasion ability in the human OVCAR3 ovarian cell line (P<0.05). In conclusion, the results indicated that the miR-196a-2 rs11614913 CC genotype may increase the risks of ovarian cancer by affecting the expression of mature miR-196a and enhancing cell migration/invasion. The current results provided evidence that the T>C polymorphism in the miR-196a-2 precursor may influence tumorigenesis and metastasis in EOC, and suggested that the functional SNP rs11614913 in the promoter region of pri-miR-196a-2 may be a potential indicator of EOC susceptibility in the population analyzed. IntroductionOvarian cancer only accounts for ~4% of cancer cases in women, but it is the eighth most common cause of cancerassociated mortality resulting from gynecological tumors worldwide (1,2). Epithelial ovarian cancer (EOC), which is categorized into serous, mucinous, endometrioid and non-clear cell types, accounts for 90% of all ovarian cancer (3,4). The earlier cancer ...

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“…5) [24][25][26][27][28]. For example, it has been proved by previous study that a higher level of miR-166 expression was observed within normal prostate tissues compared with cancer patients, which inhibited the growth of prostate tumor by regulating the expression of genes associated with cellular proliferation and cell cycle control, such as CDK1 and CDK2 [29].…”

Section: Cancer Cells Intrude Into the Blood And Lymphatic Vesselsmentioning

confidence: 90%

MicroRNAs used as novel biomarkers for detecting cancer metastasis

Han

Zhang

et al. 2014

Tumor Biol.

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The low survival rates of cancers are primarily due to late diagnosis and metastasis. Discriminating the metastasis is a crucial factor for prognosis and improving the survival rate of cancer patients. MicroRNAs (miRNAs) can regulate the expression of hundreds of downstream genes, which has a broad effect on the regulation of the whole cell cycle. Accumulating studies have found that the aberrant expression of miRNAs is associated with cancer genesis. The aim of this study is to evaluate the diagnostic value of miRNAs in detecting cancer metastasis. Medline, PubMed, Embase, and CNKI were searched for relevant articles. Sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR) and diagnostic odds ratio (DOR), the summary receiver operator characteristic (SROC) curve and the calculated AUC (area under the SROC curve) were applied to explore the diagnostic accuracy of miRNAs in metastasis. Seven hundred seventy-one metastatic cancer patients and 552 non-metastatic cancer controls from 14 articles were involved in our meta-analysis. A sensitivity of 0.75 (95% confidence interval (CI), 0.72-0.79) and a specificity of 0.80 (95% CI, 0.76-0.84) were observed from metastatic patients and non-metastatic controls in the combined analysis. And the AUC was 0.83 (95% CI, 0.79-0.86). In addition, results from subgroup analyses suggested that a higher diagnostic value for metastasis was acquired in tissue sample other than blood sample (sensitivity, 0.82 versus 0.73; specificity, 0.84 versus 0.79; PLR, 5.0 versus 3.5; NLR, 0.22 versus 0.34; DOR, 23 versus 10; AUC, 0.88 versus 0.80). In summary, this meta-analysis proved the relatively high diagnostic value of miRNA in metastasis, which might be applied as a novel screening tool to detect metastasis along with other biomarkers. We also illustrated that tissue-based miRNAs may have a better diagnostic accuracy than blood-based miRNAs.

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MicroRNA sequence polymorphisms and the risk of different types of cancer

Cited by 61 publications

References 56 publications

Small-RNA asymmetry is directly driven by mammalian Argonautes

Small-RNA asymmetry is directly driven by mammalian Argonautes

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer

MicroRNAs used as novel biomarkers for detecting cancer metastasis

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