Identification of MiR-423 and MiR-499 Polymorphisms on Affecting the Risk of Hepatocellular Carcinoma in a Large-scale Population

Overview

Journal Genet Test Mol Biomarkers

Specialties Genetics
Molecular Biology

Date 2014 May 24

PMID 24854593

Citations 21

Authors

Yanyun Ma

Rui Wang

Jun Zhang

Wenshuai Li

Chunfang Gao

Jie Liu

Jiucun Wang

Affiliations

Soon will be listed here.

Abstract

Aims: MicroRNAs (miRNAs) regulate gene expression and act as tumor suppressors or enhancers in oncogenesis. Single-nucleotide polymorphisms (SNPs) in miRNAs could alter the processing or actions of mature miRNA. So far, the association of miR-423 rs6505162 with cancers has not been explored, while the association of miR-499 rs3746444 was only reported in small-sized samples of different types of populations.

Methods: To evaluate the association of miR-499 rs3746444 and miR-423 rs6505162 with hepatocellular carcinoma (HCC), we performed a large-scale case-control study of 984 patients with HCC and 991 cancer-free controls.

Results: The risk of HCC was significantly higher with miR-499 rs3746444 TC+CC genotypes compared with those with the TT genotype (odds ratio [OR]=1.372, 95% confidence intervals [CI]=1.099-1.713, p=0.005), as was the risk of hepatitis B virus-related HCC (OR=1.437, 95% CI=1.128-1.831, p=0.003). Moreover, subjects with the TC+CC genotypes were more vulnerable to advanced HCC with larger tumor size (χ(2)=13.014, p=0.001) and/or higher total bilirubin (p=0.004), which suggested that a TT genotype or T allele might serve as a protective factor. miR-423 rs6505162 had no effect on the risk of HCC.

Conclusions: miR-499 rs3746444 may contribute to the risk and prognosis of HCC, indicating that this SNP could be developed as a biomarker for HCC prediction.

Citing Articles

The Association between Four Common Polymorphisms in microRNA and Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis.

Chen M, Lu Y, Wang X, Qin S, Chen H, Lu L Iran J Public Health. 2023; 52(11):2272-2285.

PMID: 38106842 PMC: 10719708. DOI: 10.18502/ijph.v52i11.14027.

Genetic Variation in MicroRNA-423 Promotes Proliferation, Migration, Invasion, and Chemoresistance in Breast Cancer Cells.

Morales-Pison S, Jara L, Carrasco V, Gutierrez-Vera C, Reyes J, Gonzalez-Hormazabal P Int J Mol Sci. 2022; 23(1).

PMID: 35008806 PMC: 8745459. DOI: 10.3390/ijms23010380.

MicroRNA polymorphism: A target for diagnosis and prognosis of hepatocellular carcinoma?.

Ma R, Zhao M, Zou X, Zhou J, Bai Z Oncol Lett. 2021; 21(4):324.

PMID: 33692856 PMC: 7933756. DOI: 10.3892/ol.2021.12586.

Functional mechanism and clinical implications of MicroRNA-423 in human cancers.

Ke R, Lv L, Zhang S, Zhang F, Jiang Y Cancer Med. 2020; 9(23):9036-9051.

PMID: 33174687 PMC: 7724490. DOI: 10.1002/cam4.3557.

Non-Coding RNAs as Potential Novel Biomarkers for Early Diagnosis of Hepatic Insulin Resistance.

Pielok A, Marycz K Int J Mol Sci. 2020; 21(11).

PMID: 32545342 PMC: 7313458. DOI: 10.3390/ijms21114182.

References

Saunders M, Liang H, Li W . Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci U S A. 2007; 104(9):3300-5. PMC: 1805605. DOI: 10.1073/pnas.0611347104. View

Xu Y, Liu L, Liu J, Zhang Y, Zhu J, Chen J . A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma. Int J Cancer. 2010; 128(2):412-7. DOI: 10.1002/ijc.25342. View

Lu X, Zhao H, Yang H, Mao Y, Sang X, Miao R . A prospective clinical study on early recurrence of hepatocellular carcinoma after hepatectomy. J Surg Oncol. 2009; 100(6):488-93. DOI: 10.1002/jso.21354. View

Ye Y, Wang K, Gu J, Yang H, Lin J, Ajani J . Genetic variations in microRNA-related genes are novel susceptibility loci for esophageal cancer risk. Cancer Prev Res (Phila). 2009; 1(6):460-9. PMC: 2768267. DOI: 10.1158/1940-6207.CAPR-08-0135. View

Blum H . Hepatocellular carcinoma: therapy and prevention. World J Gastroenterol. 2006; 11(47):7391-400. PMC: 4725160. DOI: 10.3748/wjg.v11.i47.7391. View

Guled M, Lahti L, Lindholm P, Salmenkivi K, Bagwan I, Nicholson A . CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma -A miRNA microarray analysis. Genes Chromosomes Cancer. 2009; 48(7):615-23. DOI: 10.1002/gcc.20669. View

Smith R, Jedlinski D, Gabrovska P, Weinstein S, Haupt L, Griffiths L . A genetic variant located in miR-423 is associated with reduced breast cancer risk. Cancer Genomics Proteomics. 2012; 9(3):115-8. View

Croce C . Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009; 10(10):704-14. PMC: 3467096. DOI: 10.1038/nrg2634. View

Guo J, Jin M, Zhang M, Chen K . A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies. PLoS One. 2012; 7(1):e30585. PMC: 3265498. DOI: 10.1371/journal.pone.0030585. View

10.

Wang J, Jiao J, Li Q, Long B, Wang K, Liu J . miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nat Med. 2010; 17(1):71-8. DOI: 10.1038/nm.2282. View

11.

Alshatwi A, Shafi G, Hasan T, Syed N, Al-Hazzani A, Alsaif M . Differential expression profile and genetic variants of microRNAs sequences in breast cancer patients. PLoS One. 2012; 7(2):e30049. PMC: 3282723. DOI: 10.1371/journal.pone.0030049. View

12.

Xing J, Wan S, Zhou F, Qu F, Li B, Myers R . Genetic polymorphisms in pre-microRNA genes as prognostic markers of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2011; 21(1):217-27. PMC: 3253954. DOI: 10.1158/1055-9965.EPI-11-0624. View

13.

Wen J, Friedman J . miR-122 regulates hepatic lipid metabolism and tumor suppression. J Clin Invest. 2012; 122(8):2773-6. PMC: 3408753. DOI: 10.1172/JCI63966. View

14.

Lafferty-Whyte K, Cairney C, Jamieson N, Oien K, Keith W . Pathway analysis of senescence-associated miRNA targets reveals common processes to different senescence induction mechanisms. Biochim Biophys Acta. 2009; 1792(4):341-52. DOI: 10.1016/j.bbadis.2009.02.003. View

15.

Buonocore F, Hill M, Campbell C, Oladimeji P, Jeffries A, Troakes C . Effects of cis-regulatory variation differ across regions of the adult human brain. Hum Mol Genet. 2010; 19(22):4490-6. PMC: 3298852. DOI: 10.1093/hmg/ddq380. View

16.

Farazi T, Horlings H, Ten Hoeve J, Mihailovic A, Halfwerk H, Morozov P . MicroRNA sequence and expression analysis in breast tumors by deep sequencing. Cancer Res. 2011; 71(13):4443-53. PMC: 3129492. DOI: 10.1158/0008-5472.CAN-11-0608. View

17.

Duan S, Mi S, Zhang W, Dolan M . Comprehensive analysis of the impact of SNPs and CNVs on human microRNAs and their regulatory genes. RNA Biol. 2009; 6(4):412-25. PMC: 2783774. DOI: 10.4161/rna.6.4.8830. View

18.

Kontorovich T, Levy A, Korostishevsky M, Nir U, Friedman E . Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high-risk women. Int J Cancer. 2009; 127(3):589-97. DOI: 10.1002/ijc.25065. View

19.

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

20.

Zhang J, Wang R, Ma Y, Chen L, Jin B, Yu H . Association between single nucleotide polymorphisms in miRNA196a-2 and miRNA146a and susceptibility to hepatocellular carcinoma in a Chinese population. Asian Pac J Cancer Prev. 2014; 14(11):6427-31. DOI: 10.7314/apjcp.2013.14.11.6427. View