Abstract
Several studies have suggested that long non-coding RNA (lncRNA) gene polymorphisms are associated with cancer risk. In the present study, we conducted a meta-analysis related to studies on the association between lncRNA single-nucleotide polymorphisms (SNPs) and the overall risk of cancer. A total of 12 SNPs in five common lncRNA genes were finally included in the meta-analysis. In the lncRNA antisense non-coding RNA (ncRNA) in the INK4 locus (ANRIL), the rs1333048 A/C, rs4977574 A/G, and rs10757278 A/G polymorphisms, but not rs1333045 C/T, were correlated with overall cancer risk. Our study also demonstrated that other SNPs were correlated with overall cancer risk, namely, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1, rs619586 A/G), HOXA distal transcript antisense RNA (HOTTIP, rs1859168 A/C), and highly up-regulated in liver cancer (HULC, rs7763881 A/C). Moreover, four prostate cancer-associated ncRNA 1 (PRNCR1, rs16901946 G/A, rs13252298 G/A, rs1016343 T/C, and rs1456315 G/A) SNPs were in association with cancer risk. No association was found between the PRNCR1 (rs7007694 C/T) SNP and the risk of cancer. In conclusion, our results suggest that several studied lncRNA SNPs are associated with overall cancer risk. Therefore, they might be potential predictive biomarkers for the risk of cancer. More studies based on larger sample sizes and more lncRNA SNPs are warranted to confirm these findings.
Highlights
As a new class of functional non-coding RNAs, long ncRNAs are made up of over 200 nts and lack the ability of protein coding [1]
ANRIL, antisense non-coding RNA in the INK4 locus; CRS, created restriction site; HOTTIP, HOXA distal transcript antisense RNA; HULC, highly up-regulated in liver cancer; HWE, Hardy–Weinberg equilibrium; LD, linkage disequilibrium; long ncRNAs (lncRNAs), long non-coding RNA; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; ncRNA, non-coding RNA; NOS, Newcastle–Ottawa scale; OR, odds ratio; PRNCR1, prostate cancer-associated non-coding RNA 1; RFLP, restriction fragment length polymorphism; SNP, single-nucleotide polymorphism; T-ARMS, tetra-primer amplification refractory mutation system; 95% CI, 95% confidence interval
The extensive clinical application of long ncRNAs (lncRNAs) polymorphisms requires further study
Summary
As a new class of functional non-coding RNAs (ncRNAs), long ncRNAs (lncRNAs) are made up of over 200 nts and lack the ability of protein coding [1]. The association between lncRNA and human diseases, especially cancer, has been widely investigated. Compared with other ncRNAs, lncRNAs play an important role in numerous vital activities of cell, including the regulation of epigenetic modifications, cell cycle, cell differentiation, and stress response [2]. The most important function of lncRNA is involvement in the tumorigenesis as proto-oncogene [3] or anti-oncogene [4]. The differential expression of lncRNA may facilitate tumor cell proliferation, invasion, and metastasis [5]. It is predicted that the expression and function of lncRNAs are affected by SNPs [6]. Studies have suggested that polymorphism in lncRNA may influence the process of splicing and stability of mRNA conformation, leading to the modification of their interacting partners [7]. Several studies have assessed the associations amongst more than 20 lncRNA polymorphisms and susceptibility of cancers, but the results are inconsistent
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