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Research Article Association Between Lncrna GAS5, MEG3, and PCAT-1 Polymorphisms and Cancer Risk: a Meta-Analysis

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Research Article Association Between Lncrna GAS5, MEG3, and PCAT-1 Polymorphisms and Cancer Risk: a Meta-Analysis Hindawi Disease Markers Volume 2020, Article ID 6723487, 13 pages https://doi.org/10.1155/2020/6723487 Research Article Association between lncRNA GAS5, MEG3, and PCAT-1 Polymorphisms and Cancer Risk: A Meta-Analysis Xiaoyan Dong ,1 Wenyan Gao,2 Xiaoling LV ,3 Yazhen Wang ,3 Qing Wu ,3 Zhouxin Yang ,3 Genxiang Mao ,3 and Wenmin Xing 3 1Department of Pharmacy and Medicine Pharmacy, Jiang Su College of Nursing, Huian, 223003, China 2Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China 3Zhejiang Provincial Key Lab of Geriatrics, Department of Geriatrics, Zhejiang Hospital, Hangzhou 310013, China Correspondence should be addressed to Genxiang Mao; [email protected] and Wenmin Xing; [email protected] Received 27 June 2019; Revised 15 October 2019; Accepted 28 November 2019; Published 28 March 2020 Guest Editor: Ioannis Kosmas Copyright © 2020 Xiaoyan Dong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Purpose. Long noncoding RNAs (lncRNAs) have been widely studied, and single nucleotide polymorphisms (SNPs) in lncRNAs are considered to be genetic factors that influence cancer susceptibility. The lncRNA GAS5, MEG3, and PCAT-1 polymorphisms are shown to be possibly associated with cancer risk. The aim of this meta-analysis was to systematically evaluate this association. Methods. Studies were selected from PubMed, Web of Science, Embase, Google Scholar, Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM) through inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the random-effects model or fixed-effects model to assess the association between lncRNA polymorphisms and cancer susceptibility. Metaregression and publication bias analyses were also conducted. All analyses were performed using the Stata 12.0 software. Results. Sixteen articles (covering 13750 cases and 17194 controls) were included in this meta-analysis. A significant association between SNP rs145204276 and gastric cancer risk was observed (del vs. ins: OR = 0:79, 95%CI = 0:72‐0:86; del/del vs. ins/ins+del/ins: OR = 0:74, 95%CI = 0:59‐0:91; del/ins vs. ins/ins: OR = 0:84, 95%CI = 0:67‐1:05). For rs16901904, a decreased cancer risk was observed in three genetic models (C vs. T: OR = 0:79, 95%CI = 0:70‐0:90; CC vs. CT+TT: OR = 0:49, 95%CI = 0:37‐0:65; CC vs. TT: OR = 0:49, 95%CI = 0:37‐0:66). No statistical significance was found in the metaregression analysis. For all of the included SNPs, no publication bias was found in all genotype models. Conclusions. The rs145204276 SNP in lncRNA GAS5 is likely to be associated with gastric cancer risk, whereas the rs16901904 SNP in lncRNA PCAT-1 bears association with a decreased cancer risk. 1. Introduction cal mechanisms of cancer development, such as genetic bio- markers which can be used as prognostic factors for cancer Cancer has become a leading cause of death worldwide not patients [4]. only in high-income but also in middle-income countries High-throughput sequencing technologies have identi- [1, 2]. Due to the growth of the aging population, the cancer fied a great number of noncoding RNAs in the genome, burden is expanding in many countries; there were about which could be classified into small (18-200 nts) and long 18.1 million new cancer cases and 9.6 million cancer deaths (200 nts to >100 kb) noncoding RNAs (lncRNAs) [5]. in 2018 [3]. Many investigators have devoted much effort Although lncRNAs have once been viewed as “transcrip- to reducing cancer mortality and morbidity. For example, tional noise” or “dark matter” in the genome, an abnormal in clinical therapy, surgical resection is an effective treatment expression of lncRNAs virtually plays a vital role in cancer for localized tumors, but the disease could still exhibit poten- pathogenesis, such as in cancer initiation, progression, and tial regional or distant metastasis, or high resistance toward metastasis [6]. Studies suggested that genetic variation also conventional chemotherapy and radiotherapy. Therefore, played important roles in the development of many types of researchers have focused on the potential molecular biologi- cancer. Single nucleotide polymorphisms (SNPs), a common 2 Disease Markers type of genetic variation, present in lncRNAs have been in order to summarize all eligible studies and evaluate the found to be able to affect the structure, expression level, overall relation between cancer risk and lncRNA (GAS5, and function of lncRNAs by interfering with the correspond- PCAT-1, and MEG3) polymorphisms. ing target mRNAs [7]. Evidence has demonstrated that SNPs in lncRNA genes were related to the occurrence of various 2. Material and Methods diseases, particularly cancer [8]. Therefore, lncRNA poly- morphisms are considered to be potentially associated with 2.1. Search Strategy. Two investigators independently con- the mechanism underlying cancer susceptibility. ducted an electronic literature search (published before April Recently, research showed that GAS5 overexpression 20, 2019) using PubMed, Web of Science, Embase, Google could inhibit the invasive ability of hepatocarcinoma cells Scholar, Cochrane Library, the Chinese National Knowledge affecting the epithelial-mesenchymal transition (EMT) pro- Infrastructure (CNKI), and the Chinese Biomedical Literature cess, which is very important in early events of the metastatic Database (CBM). The restriction in publication languages spread of tumor cells and can make cells more active and inva- was selected as English and Chinese. During our search pro- sive [9]. Meanwhile, colorectal cancer (CRC) cell growth and cess, the following keywords were used: “lncRNA GAS5,” colony formation were also inhibited by the induction of cell “lncRNA MEG3,”“lncRNA PCAT-1,”“polymorphism,” cycle G0/G1 arrest and apoptosis [10], increasing casp9 “Single nucleotide polymorphism,”“genetic variant,”“can- mRNA and pho-Casp9 protein and decreasing extracellular- cer,”“tumor,”“malignancy,”“carcinoma,” and “neoplasm.” regulated protein kinases (ERK), Casp3 mRNA, p-Akt, All clearly irrelevant studies such as case reports and review p-ERK, and pho-Casp3 proteins [11]. However, the down- articles were excluded. The relevant studies cited in the regulation of GAS5 expression accelerates depletion of the references of review articles were also manually searched YBX1 protein and decreases the expression of p21, thereby for additional eligible studies. eliminating G1 arrest to control the proliferation of gastric cancer [12]. A functional 5-base pair (AGGCA/-) insertion/- 2.2. Study Selection. Two researchers independently evalu- deletion (indel) polymorphism (rs145204276) that exists in ated the titles and abstracts of the identified articles to decide the promoter region of lncRNA growth arrest-specific5 whether they met the study criteria. Differences were solved (lncRNA GAS5) has been investigated in multiple cancer by consensus. Both cross-sectional and longitudinal studies types [13–23]. A deletion (del) allele appears to enhance gene on the relationship between SNPs in lncRNAs GAS5, transcription activity when compared to an insertion (ins) MEG3, and PCAT-1 and cancer risk were included. Studies allele [15]. Zheng et al. performed a two-stage, case-control were included in this meta-analysis only when they met the study to investigate the association between lncRNA GAS5 following criteria: (1) the study evaluated the association of polymorphisms (rs145204276) and CRC risk, and the results SNPs in lncRNAs GAS5, MEG3, and PCAT-1 with cancer indicated that the del allele of rs145204276 was significantly risk; (2) the study was published in Chinese or English lan- associated with a 21% decreased risk of CRC [21]. However, guage; (3) the study had an original case-control design or logistic regression analysis showed that the deletion allele of was a cohort-designed study in humans; (4) the study pro- rs145204276 significantly increased the risk of hepatocellular vided sufficient genotyping data to estimate ORs and 95% carcinoma (HCC) in two independent case control sets CIs; (5) genotype frequencies of subjects in controls were in (1034 HCCs and 1054 controls) [18]. accordance with the Hardy-Weinberg equilibrium (HWE); Furthermore, lncRNAs such as GAS5, H19, MEG3, and (6) all cancer cases were diagnosed at any stage by pathology, TUSC7 play oncogenic or tumor suppressor roles in corre- but only primary tumor could be involved. If there was a lation with tumor suppressor protein P53 or oncoprotein parallel publication, we selected the study with a larger c-Myc, respectively [24]. Balci et al. discovered that PCAT-1, sample size. ANRIL, and H19 could inhibit glioblastoma (GBM) cell Studies were excluded if (1) they were not case-control proliferation, invasion, and migration. Conversely, primary studies; (2) they were case reports, comments, meta-analyses, tumors in GBMs displaying tumor progression were charac- or review articles; (3) they were a previous study that was terized by increased MEG3 and HOTAIR expression levels duplicated; (4) they were the control groups that did not con- [25]. SNPs in lncRNA prostate cancer-associated lncRNA form to HWE; (5) there were not enough genotyping data to transcript 1 (PCAT-1), such as rs1902432, rs16901904, calculate the ORs and 95% CIs; and (6) they were
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