长链非编码RNA H19在肿瘤研究中的进展

近年来研究发现长链非编码RNA H19在肿瘤发生发展中起到非常重要的作用。H19在胃癌、膀胱癌等肿瘤中发挥癌基因的作用,促进肿瘤增殖和转移;在肝癌和前列腺癌中却发挥抑癌基因的作用。H19的功能较为复杂,有可能作为肿瘤诊断、预后及药物敏感性的生物标记。本文结合国内外最新研究报道,对H19在肿瘤研究中的进展作一综述。     

长链非编码RNA H19表达与恶性肿瘤患者预后关系的Meta分析

目的 采用Meta分析方法综合评价长链非编码RNA(lncRNA)H19与恶性肿瘤患者预后的关系.方法 计算机检索PubMed、EMBASE、中国知网、万方数据库、维普数据库,检索日期截至2020年8月31日.采用Review Manager 5.3软件进行数据分析.结果 共纳入16篇文献,样本量为1741例.Meta...     

长链非编码RNA H19在肿瘤中的研究进展

摘 要：长链非编码RNA是目前肿瘤研究中的热点,在表观遗传学、基因转录和转录后调控等多方面影响肿瘤的发生发展。H19是一个典型的长链非编码RNA,在多种肿瘤中表达异常,而且在不同肿瘤中发挥的作用也不尽相同。同时,H19在肿瘤诊断和治疗方面的研究也显示其具有广泛的应用前景。本文归纳了H19的作用机制,并对其在肿瘤中的作用及在临床肿瘤诊治中的应用作一综述。     

长链非编码RNA在前列腺癌中的研究进展

长链非编码RNAs(long non-coding RNAs,lncRNAs)是类转录本长度超过200 nt、无蛋白编码功能的非编码RNA分子,lncRNAs可通过多种机制发挥生物学功能。LncRNAs与人类肿瘤的发生密切相关,可在表观遗传水平、转录水平及转录后水平调控基因的表达。目前有较多研究表明,lncRNAs广泛参与机体的生理和病理过程,在恶性肿瘤的发生和发展中起着重要作用。本文就lncRNAs在前列腺癌中的研究进展进行简要综述。     

长链非编码RNA H19在妇科肿瘤中的研究进展

随着研究进展,长链非编码RNAs在疾病中的作用越来越受到重视,成为最新研究热点.其中H19是第一个被发现与癌症密切相关的lncRNA,在胚胎时期高表达,出生后表达减退,而在肿瘤中又重新出现,并积极参与到肿瘤发生发展的各个环节.尽管越来越多的证据支持H19是重要的癌基因之一,但其在肿瘤中的作用一直存在争议.本文综述H19在常见妇科肿瘤领域的研究进展,为妇科常见肿瘤的诊断、治疗及预后评估提供新的依据和方向.     

长链非编码RNA与肺癌

长链非编码RNA（lncRNA）是一类转录本长度超过200个核苷酸的小分子RNA,不具有蛋白编码功能,起初被认为是基因组转录的“噪音”,近年来却被证实在生物体内对基因的表达具有调控作用,与肿瘤的发生发展密切相关。肺癌是一种严重危害人们健康的恶性肿瘤性疾病,研究发现lncRNA在肺肿瘤中表达失调,异常表达的lncRNA能作为关键的调控因子,参与多种生物学过程,影响肿瘤转移与侵袭、肺癌细胞的增殖和凋亡、肿瘤血管生成及调节肿瘤耐药,为肺癌临床治疗提供新思路。此外,lncRNA还可作为潜在的生物标志物用于肺癌早期诊断及评估肺癌预后。本文就lncRNA在肺癌研究中的进展进行综述。     

长链非编码RNA与肿瘤

长链非编码RNA （IncRNA）是重要的基因表达调控因子,它广泛参与多种生理及病理过程.近年来研究证实IncRNA与肿瘤密切相关,并显露出作为肿瘤诊断和治疗新靶点的潜能.     

长链非编码RNA与乳腺癌关系的研究进展

乳腺癌作为女性最常见的恶性肿瘤,严重威胁女性的生命健康。研究表明,多种长链非编码RNA通过靶点基因的上调或下调,在乳腺癌细胞中异常表达,进而调控乳腺癌细胞的增殖、转移、凋亡及耐药等。     

长链非编码RNA PVT1在肿瘤中的研究进展

长链非编码RNA（lncRNA）在肿瘤的发生、发展过程中起着重要作用。lncRNA PVT1在乳腺癌、肝细胞癌、胃癌、结肠癌等多种肿瘤中高表达,并发挥多种生物学功能,如竞争内源性RNA、维持重要癌基因蛋白的稳定性、参与肿瘤化疗耐药等。本文对lncRNA PVT1在肿瘤中的表达形式、所发挥的生物学功能及其分子机制作一综述。     

Significant association of methylenetetrahydrofolate reductase single nucleotide polymorphisms with prostate cancer susceptibility in taiwan

Prostate cancer is the most common cause of cancer death in men and is a major health problem worldwide. Methylene tetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and is also an important source of DNA methylation and DNA synthesis (nucleotide synthesis). To assess the association and interaction of genotypic polymorphisms in MTHFR and lifestyle factors with prostate cancer in Taiwan, we investigated two well-known polymorphic variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), analyzed the association of specific genotypes with prostate cancer susceptibility, and discussed their joint effects with individual habits on prostate cancer risk. In total, 218 patients with prostate cancer and 436 healthy controls recruited from the China Medical Hospital in central Taiwan were genotyped for these polymorphisms with prostate cancer susceptibility. We found the MTHFR C677T but not the A1298C genotype was differently distributed between the prostate cancer and control groups. The T allele of MTHFR C677T conferred a significantly (p=0.0011) decreased risk of prostate cancer. As for the A1298C polymorphism, there was no difference in distribution between the prostate cancer and control groups. Gene interactions with smoking were significant for MTHFR C677T polymorphism. The MTHFR C677T CT and TT genotypes in association with smoking conferred a decreased risk of 0.501 (95% confidence interval=0.344-0.731) for prostate cancer. Our results provide the first evidence that the C allele of MTHFR C677T may be associated with the development of prostate cancer and may be a novel useful marker for primary prevention and anticancer intervention.     

Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility to prostate cancer.

The endothelial cell-specific form of nitric oxide synthases (ecNOS) is localized at 7q35-q36 and is involved in vascular development and tumour growth in human prostate cancer. We have conducted a case-control study to investigate the prevalence of two polymorphisms at intron 4 (ecNOS4a/b) and exon 7 (Glu-Asp298) of ecNOS gene in 125 prostate cancer (PCa) patients and in 153 controls. We observed that the a-allele (aa or ab genotypes from ecNOS4a/b) was over-presented in the group of PCa with Gleason histological grade >or=7 (P=0.041). With regard to the Glu-Asp298 polymorphism, patients with the T-allele were younger than patients with no T-allele (P=0.037), and a statistically significant difference was noted in the Glu-Asp298 genotype distribution between cases with advanced disease and cases with localized disease (P=0.0013). When comparing cases and controls with logistic regression analysis we observed that the presence of the a-allele is associated with prostate cancer risk (odds ratio (OR) 1.83; 95% confidence interval (CI) 1.06-3.17; P=0.029), to high histological grade (Gleason >or=7) of PCa (OR 2.18; 95% CI 0.95-4.98; P=0.062) and with the risk of progression of the cancer disease (OR 2.85; 95% CI 1.19-6.82; P=0.018). Furthermore, we found that carriers with the combination of the a-allele (aa and ab ecNOS4a/b genotypes) and T-allele (GT and TT from Glu-Asp298) have a threefold increase in prostate cancer risk (OR 3.13; 95% CI 1.41-6.91, P=0.004). In summary, we have identified an NO-related genetic risk factor for prostate cancer that may help in understanding the molecular mechanism involved in the individual susceptibility to prostate cancer.     

N-acetyltransferase-2 gene polymorphisms and prostate cancer susceptibility in Latin American patients

We investigated the role of N-acetyltransferases (NAT) in prostate cancer (PCa) susceptibility. NAT are polymorphic in the population and metabolize important carcinogenic products directly involved in the tumor initiation process. This prospective case-control study utilized the polymerase chain reaction-based restriction fragment length polymorphism method and comprised a cohort of consecutive 478 individuals: 126 men with prostate cancer; 101 men with benign prostatic hyperplasia (BPH); and a control health population of 177 female and 74 male blood donors from the same region. NAT2 slow or fast acetylators genotypes were determined by the combination of four variant alleles. Lifetime occupational history, dietary patterns, cigarette smoking and other anamnestic data were obtained by interviews. We were not able to find any correlation among smoking, dietary patterns, parameters of tumor aggressiveness or patient outcome and any NAT2 genotypes or phenotypes considered in separate or in different combinations. However, there was an association between NAT2T481C (OR?=?0.47; 95% CI?=?0.26-0.84; P?=?0.01) and NAT2A803G (OR?=?0.57; 95% CI?=?0.33-0.97; P?=?0.04) polymorphisms and PCa protection. Conversely, the presence of NAT2G857A genotype increased the risk of PCa more than 3 times (OR?=?3.57; 95% CI?=?1.39-9.15; P?=?0.005). Slow acetylator NAT2*7A and NAT2*6B genotypes occurred in 10.31% of PCa but in none of BPH patients (P?=?0.0007). The control health population confirmed the results and allowed the exclusion of possible biases caused by gender influence on genotype inheritance and by the inclusion of not diagnosed prostate diseases patients among the control individuals. We suggest that the investigation of germline polymorphisms of NAT2 gene may be useful in the assessment of Latin American patients at risk of BPH and PCa.     

Possible association of β2- and β3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer

Background  

The involvement of β₂-adrenergic receptor (ADRB2) and β₃-adrenergic receptor (ADRB3) in both adipocyte lipolysis and thermogenic activity suggests that polymorphisms in the encoding genes might be linked with interindividual variation in obesity, an important risk factor for postmenopausal breast cancer. In order to examine the hypothesis that genetic variations in ADRB2 and ADRB3 represent interindividual susceptibility factors for obesity and breast cancer, we conducted a hospital-based, case-control study in the Aichi Cancer Center, Japan.     

Single nucleotide polymorphisms in breast cancer susceptibility gene 1 are associated with susceptibility to lung cancer

BRCA1 is a tumor suppressor that has been found to be involved DNA synthesis during cell replication. In a recent study, the single nucleotide polymorphism (SNP), rs799917, in BRCA1 was found to be associated with the development and progression of various types of tumor. In the present study, the association between rs799917 and susceptibility to lung cancer was evaluated in a Han Chinese population in the Liaoning Province of China. The BRCA1 rs799917 genotypes (C/C, C/T and T/T) were analyzed using TaqMan quantitative PCR in 682 patients with lung cancer and 694 healthy controls, and the results were analyzed using a Student''s t-test, a χ² test and logistic regression analysis. Individuals carrying the C/T or T/T genotype had a lower risk of lung cancer compared with those carrying the C/C genotype [odds ratio (OR), 0.741; P=0.021; and OR, 0.610; P=0.011, respectively). The C/T + T/T genotype group had an even lower risk (OR, 0.709; P=0.005) compared with that in the C/C genotype group. In the stratified analyses of non-smokers, individuals with the C/T or T/T genotype had a lower risk of developing lung cancer compared with that in those carrying the C/C genotype (OR, 0.681; P=0.013; and OR, 0.569; P=0.021, respectively). The stratified analyses of the BRCA1 rs799917 polymorphism based on pathological type, chemotherapy and radiotherapy, showed that in the squamous cell carcinoma, non-chemotherapy and non-radiotherapy subgroups, individuals with the T/T genotype had a lower risk of lung cancer compared with that in those carrying the C/C genotype (OR, 0.454; P=0.007; OR, 0.485; P=0.002; and OR, 0.599; P=0.020, respectively). In conclusion, the T allele of the rs799917 SNP in BRCA1 was associated with a lower risk of lung cancer in the ethnic Han Chinese population in Liaoning Province and may represent a protective factor against lung cancer.     

Identification of genetic polymorphisms at the glutathione S- transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer

Two variant glutathione S-transferase cDNAs have been described at the GSTP1 locus, which differ by a single base pair (A-G) substitution at nucleotide 313 of the GSTP1 cDNA. This results in an amino acid substitution which alters the function of the enzyme. In this study, a novel PCR assay has been developed which demonstrates that these two variant cDNAs represent distinct GSTP1 alleles (GSTP1a and GSTP1b). In a study of individuals with different forms of cancer, the GSTP1b allele is found to be strongly associated with bladder cancer and testicular cancer. In controls 6.5% of individuals were homozygous for the GSTP1b allele. In bladder cancer cases, this rose to 19.7% [n = 71, odds ratio 3.6 (1.4-9.2), P = 0.006] and in testicular cancer to 18.7% [n = 155, odds ratio 3.3 (1.5-7.7), P = 0.002]. In addition, in prostate cancer a highly significant decrease in the frequency of the GSTP1a homozygotes was observed [control 51.0% versus 27.8% cancer cases, n = 36, odds ratio 0.4 (0.02-3.3), P = 0.008]. Increases in the frequency of GSTP1b homozygotes was also observed in lung cancer and chronic obstructive pulmonary disease. However, these were not statistically significant. No change in breast or colon cancer allele frequencies was observed.      

Mutation screening and association study of RNASEL as a prostate cancer susceptibility gene

To date, germline mutations have been found in three candidate genes for hereditary prostate cancer: ELAC2 at 17p11, RNASEL at 1q25 and MSR1 at 8p22. RNASEL, encoding the 2',5'-oligoadenylate-dependant RNase L, seems to have rare mutations in different ethnicities, such as M1I in Afro-Americans, E265X in men of European descent and 471delAAAG in Ashkenazi Jews. In order to evaluate the relevance of RNASEL in the German population, we sequenced its open reading frame to determine the spectrum and frequency of germline mutations. The screen included 303 affected men from 136 Caucasian families, of which 45 met the criteria for hereditary prostate cancer. Variants were analysed using a family-based association test, and genotyped in an additional 227 sporadic prostate cancer patients and 207 controls. We identified only two sib pairs (1.4% of our families) cosegregating conspicuous RNASEL variants with prostate cancer: the nonsense mutation E265X, and a new amino-acid substitution (R400P) of unknown functional relevance. Both alleles were also found at low frequencies (1.4 and 0.5%, respectively) in controls. No significant association of polymorphisms (I97L, R462Q and D541E) was observed, neither in case-control analyses nor by family-based association tests. In contrast to previous reports, our study does not suggest that common variants (i.e. R462Q) modify disease risk. Our results are not consistent with a high penetrance of deleterious RNASEL mutations. Due to the low frequency of germline mutations present in our sample, RNASEL does not have a significant impact on prostate cancer susceptibility in the German population.     

Lack of association of IL-10 gene polymorphisms with prostate cancer: evidence from 11,581 subjects

Published data on the association between interleukin-10 (IL-10) gene polymorphisms and prostate cancer (PCa) are inconclusive. To derive a more precise estimation of the association, we conducted a meta-analysis. Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database and Chinese Biomedical Literature Database, with the last report up to September 2010. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of association. A total of 13 separate studies including 5503 cases and 6078 controls based on the search criteria were involved in this meta-analysis. Meta-analysis was performed for three IL-10 gene polymorphisms (rs1800896, rs1800871, and rs1800872). We found no association between IL-10 gene rs1800896 polymorphism and PCa in overall population (G versus A: OR = 1.00, 95%CI = 0.91-1.10, P = 0.99; AG + GG versus AA: OR = 1.18, 95%CI = 0.97-1.43, P = 0.10; GG versus AA + AG: OR = 1.04, 95%CI = 0.86-1.26, P = 0.67). In subgroup analysis, similar results were found in Caucasian (G versus A: OR = 0.99, 95%CI = 0.84-1.18, P = 0.92; AG + GG versus AA: OR = 1.32, 95%CI = 0.90-1.94, P = 0.16; GG versus AA + AG: OR = 1.07, 95%CI = 0.89-1.28, P = 0.48), and Asian (G versus A: OR = 0.97, 95%CI = 0.78-1.20, P = 0.78; AG + GG versus AA: OR = 1.07, 95%CI = 0.79-1.45, P = 0.65; GG versus AA + AG: OR = 1.24, 95%CI = 0.38-4.07, P = 0.73) populations. We did not detect an association between IL-10 gene rs1800871 polymorphism and PCa in overall population (T versus C: OR = 0.96, 95%CI = 0.85-1.08, P = 0.51; CT + TT versus CC: OR = 0.94, 95%CI = 0.80-1.11, P = 0.48; TT versus CC + CT: OR = 0.94, 95%CI = 0.81-1.10, P = 0.44). Similar results were found in Asian population (T versus C: OR = 0.85, 95%CI = 0.71-1.09, P = 0.09; CT + TT versus CC: OR = 0.72, 95%CI = 0.52-1.17, P = 0.05; TT versus CC + CT: OR = 0.89, 95%CI = 0.68-1.17, P = 0.39). We found no association between IL-10 gene rs1800872 polymorphism and PCa in overall population (A versus C: OR=1.03, 95%CI = 0.96-1.11, P = 0.41; CA + AA versus CC: OR = 1.04, 95%CI = 0.92-1.17, P = 0.56; AA versus CC + CA: OR = 1.02, 95%CI = 0.85-1.22, P = 0.87). Similar results were found in Caucasian population (A versus C: OR = 1.06, 95%CI = 0.98-1.16, P = 0.16; CA + AA versus CC: OR = 1.07, 95%CI = 0.85-1.35, P = 0.57; AA versus CC + CA: OR = 1.23, 95%CI = 0.92-1.64, P = 0.17). This meta-analysis suggests that there is no association between IL-10 gene rs1800896, rs1800871 and rs1800872 polymorphisms and PCa.