Yuqin Pan

The association between four genetic variants in microRNAs (rs11614913, rs2910164, rs3746444, rs2292832) and cancer risk: evidence from published studies.

MicroRNAs (miRNAs) participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to cancer development with changes in the microRNAs properties and/or maturation. Polymorphisms in miRNAs have been suggested in predisposition to cancer risk; however, accumulated studies have shown inconsistent conslusionss. To further validate determine whether there is any potential association between the four common SNPs (miR-196a2C>T, rs11614913; miR-146aG>C, rs2910164; miR-499A>G, rs3746444; miR-149C>T, rs2292832) and the risk for developing risk, a meta-analysis was performed according to the 40 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the extent of the association. The results demonstrated that the rs11614913TT genotype was significantly associated with a decreased cancer risk, in particular with a decreased risk for colorectal cancer and lung cancer, or for Asian population subgroup. In addition, the rs2910164C allele was associated with decreased risk for esophageal cancer, cervical cancer, prostate cancer, and hepatocellular carcinoma (HCC), in particular in Asian population subgroup. Similarly, the rs3746444G allele was observed as a risk factor for cancers in the Asian population. It is concluded that two SNPs prsent in miRNAs(rs11614913TT, and rs2910164C) may protect against the pathogenesis of some cancers, and that the rs3746444 may increase risk for cancer.

Effects of genetic variations in the Adiponectin pathway genes on the risk of colorectal cancer in the Chinese population

BackgroundDecreased expression of adiponectin (ADIPOQ) is associated with an increased risk for developing colorectal cancer (CRC) in humans. This study was designed to determine whether polymorphisms present in the ADIPOQ and its type 1 receptor (ADIPOR1) could affect the risk of CRC.MethodsWe measured five polymorphisms in the ADIPOQ and two polymorphisms in ADIPOR1, and analyzed their associations with CRC risk in 420 CRC patients and 555 age- and gender-matched healthy individuals.ResultsMultivariate logistic regression analyses revealed that the CRC risks (adjusted odds ratio and 95% confidence interval) associated with the ADIPOR1 genotypes were 0.53 (95% CI, 0.35-0.81) for rs12733285C/T, 0.59 (95% CI, 0.45-0.78) for rs1342387A/G, and 0.59 (95% CI, 0.39-0.89) for rs1342387A/A, respectively. Furthermore, the risks were more significant in carriers of the allele A of rs1342387A/G (adjusted OR, 0.59; 95% CI, 0.46-0.77) than noncarriers (G/G). In a further subgroup analysis, we observed that rs266729G/C was associated with an increased risk for colon cancer (adjusted OR, 1.50; 95% CI, 1.05-2.14) but not for rectal cancer (adjusted OR, 0.88; 95% CI, 0.63-1.22), and that carriers of the G allele had an increased risk for developing colon cancer (adjusted OR, 1.45; 95% CI, 1.03-2.05).ConclusionsWe conclude that the rs12733285C/T genotype and the carriage of the A allele of rs1342387 (A/G or A/A) in ADIPOR1 are the protective factors for CRC, while that rs266729G/C and G allele of ADIPOQ are the risk factors for colon cancer after excluding rectal cancer cases.

Up-regulation of 91H promotes tumor metastasis and predicts poor prognosis for patients with colorectal cancer.

Background Long noncoding RNAs (lncRNAs) play widespread roles in gene regulation and cellular processes. However, the functional roles of lncRNAs in colorectal cancer (CRC) are not yet well elucidated. The aim of the present study was to measure the levels of lncRNA 91H expression in CRC and evaluate its clinical significance and biological roles in the development and progression of CRC. Methods 91H expression and copy number variation (CNV) were measured in 72 CRC tumor tissues and adjacent normal tissues by real-time PCR. The biological roles of 91H were evaluated by MTT, scratch wound assay, migration and invasion assays, and flow cytometry. Results 91H was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Moreover, 91H overexpression was closely associated with distant metastasis and poor prognosis in patients with CRC, except for CNV of 91H. Multivariate analysis indicated that 91H expression was an independent prognostic indicator, as well as distant metastasis. Our in vitro data indicated that knockdown of 91H inhibited the proliferation, migration, and invasiveness of CRC cells. Conclusions 91H played an important role in the molecular etiology of CRC and might be regarded as a novel prognosis indicator in patients with CRC.

Prognostic value of neutrophil‐to‐lymphocyte ratio in breast cancer

Inflammation is an essential component of pathogenesis and progression of cancer. A high neutrophil‐to‐lymphocyte ratio (NLR) is considered as a prognostic indicator for breast cancer. This meta‐analysis was conducted to establish the overall accuracy of the NLR test in the diagnosis of breast cancer. A comprehensive search of the literature was conducted by using PubMed, Web of Science and China National Knowledge Infrastructure (CNKI). Published studies dating up to July 2014 and 4,293 patients were enrolled in the present study. In order to evaluate the association between NLR and overall survival (OS), disease‐free survival (DFS), recurrence‐free survival (RFS) or cancer specific survival (CSS), the hazard ratios (HRs) and their 95% confidence intervals (CIs) were extracted. OS was the primary outcome. The results suggested that increased NLR was a strong predictor for OS with HR of 2.28 (95% CI = 1.08–4.80,Pheterogeneity < 0.001). Stratified analyses indicated that a high NLR appeared to be a negative prognostic marker in Caucasian populations (HR = 4.53, 95% CI = 3.11–6.60,Pheterogeneity = 0.096), multivariate analysis method (HR = 2.10, 95% CI = 1.52–2.89,Pheterogeneity = 0.591), and mixed metastasis (HR = 4.53, 95% CI = 3.11–6.60,Pheterogeneity = 0.096). Elevated NLR was associated with a high risk for DFS (HR = 1.38, 95% CI = 1.09–1.74,Pheterogeneity = 0.050) and in subgroups of multivariate analysis (HR = 1.64, 95% CI = 1.25–2.14,Pheterogeneity = 0.545) and mixed metastasis (HR = 1.99, 95% CI = 1.28–3.09,Pheterogeneity = 0.992). In summary, NLR could be considered as a predictive factor for patients with breast cancer.

CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7

Mounting evidences indicate that circular RNAs (circRNAs) have a vital role in human diseases, especially cancers. More recently, circHIPK3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, its role in colorectal cancer (CRC) has not been explored. In this study, we found circHIPK3 was significantly upregulated in CRC tissues and cell lines, at least in part, due to c-Myb overexpression and positively correlated with metastasis and advanced clinical stage. Moreover, Cox multivariate survival analysis showed that high-level expression of circHIPK3 was an independent prognostic factor of poor overall survival (OS) in CRC (hazard ratio [HR] = 2.75, 95% confidence interval [CI] 1.74–6.51, p = 0.009). Functionally, knockdown of circHIPK3 markedly inhibited CRC cells proliferation, migration, invasion, and induced apoptosis in vitro and suppressed CRC growth and metastasis in vivo. Mechanistically, by using biotinylated-circHIPK3 probe to perform RNA pull-down assay in CRC cells, we identified miR-7 was the only one microRNA that was abundantly pulled down by circHIPK3 in both HCT116 and HT29 cells and these interactions were also confirmed by biotinylated miR-7 pull-down and dual-luciferase reporter assays. Overexpression of miR-7 mimicked the effect of circHIPK3 knockdown on CRC cells proliferation, migration, invasion, and apoptosis. Furthermore, ectopic expression of circHIPK3 effectively reversed miR-7-induced attenuation of malignant phenotypes of CRC cells by increasing the expression levels of miR-7 targeting proto-oncogenes (FAK, IGF1R, EGFR, YY1). Remarkably, the combination of circHIPK3 silencing and miR-7 overexpression gave a better effect on tumor suppression both in vitro and in vivo than did circHIPK3 knockdown or miR-7 overexpression alone. Taken together, our data indicate that circHIPK3 may have considerable potential as a prognostic biomarker in CRC, and support the notion that therapeutic targeting of the c-Myb/circHIPK3/miR-7 axis may be a promising treatment approach for CRC patients.

Systematic review and meta-analysis on vitamin D receptor polymorphisms and cancer risk

The vitamin D receptor (VDR) can influence cancer susceptibility through binding to vitamin D. However, the previous studies were contradictory. Therefore this meta-analysis was conducted to clarify the association between VDR polymorphisms (BsmI, TaqI, FokI, and ApaI) and cancer risk. One hundred twenty-six studies were enrolled through PubMed. For VDR BsmI polymorphism, significantly increased cancer risks were observed in the overall analysis. In the further stratified analysis, increased risks were observed in colorectal and skin cancer, especially in Caucasian population. However, no significant associations were observed in other VDR polymorphisms in the overall analysis. In the further subgroup analysis, increased risks were found in oral, breast, and basal cell cancer while decreased risk was found in prostate cancer in t allele carriers of TaqI polymorphism. For VDR FokI polymorphism, increased risks were found in ovarian and skin cancer while decreased risk in glioma in f allele carriers. For VDR ApaI polymorphism, increased risk was observed in basal cell cancer, especially in Asian population in a allele carriers. In conclusion, these results indicated that b allele of BamI polymorphism was a risk factor for cancer susceptibility. Meanwhile, t allele of TaqI polymorphism was a risk factor for oral, breast, and basal cell cancer and a protective factor for prostate cancer. Moreover, f allele of FokI polymorphism was a risk factor for ovarian and skin cancer and a protective factor for glioma. Finally, a allele of ApaI polymorphism was a risk factor for basal cell cancer in Asian population.

RNAi-mediated silencing of CD147 inhibits tumor cell proliferation, invasion and increases chemosensitivity to cisplatin in SGC7901 cells in vitro.

BackgroundCD147 is a widely distributed cell surface glycoprotein that belongs to the Ig superfamily. CD147 has been implicated in numerous physiological and pathological activities. Enriched on the surface of many tumor cells, CD147 promotes tumor growth, invasion, metastasis and angiogenesis and confers resistance to some chemotherapeutic drugs. In this study, we investigated the possible role of CD147 in the progression of gastric cancer.MethodsShort hairpin RNA (shRNA) expressing vectors targeting CD147 were constructed and transfected into human gastric cancer cells SGC7901 and CD147 expression was monitored by quantitative realtime RT-PCR and Western blot. Cell proliferation, the activities of MMP-2 and MMP-9, the invasive potential and chemosensitivity to cisplatin of SGC7901 cells were determined by MTT, gelatin zymography, Transwell invasion assay and MTT, respectively.ResultsDown-regulation of CD147 by RNAi approach led to decreased cell proliferation, MMP-2 and MMP-9 activities and invasive potential of SGC7901 cells as well as increased chemosensitivity to cisplatin.ConclusionCD147 involves in proliferation, invasion and chemosensitivity of human gastric cancer cell line SGC7901, indicating that CD147 may be a promising therapeutic target for gastric cancer.

Different Effects of Three Polymorphisms in MicroRNAs on Cancer Risk in Asian Population: Evidence from Published Literatures

MicroRNAs (miRNAs) are a class of small non-protein-coding RNAs, which have emerged as integrated and important post-transcriptional regulators of gene expression. It has been demonstrated that single nucleotide polymorphisms (SNPs) exist in protein-coding genes. Accumulated studies have evaluated the association of miRNA SNPs with cancer risk, especially in Asian population, which included a series of related studies. However, the results remain controversial for the different genetic backgrounds, living habits and environment exposed. To evaluate the relationship between SNPs in miRNAs and cancer risk, 21 studies focused on Asian population were enrolled for the pooled analysis for three polymorphisms rs2910164, rs11614913, rs3746444 in three miRNAs miR-146aG>C, miR-196a2C>T, miR-499A>G using odds ratios (ORs) with 95% confidence intervals (CIs). For rs2910164 polymorphism, C allele was observed association with decreased overall cancer risk. In addition, subgroup analysis revealed of rs2910164 C allele decreased hepatocellular carcinoma (HCC), cervical cancer and prostate cancer risk among Chinese population. For rs11614913 polymorphism, TT genotype was observed to be associated with decreased cancer risk, especially for cancer type of colorectal cancer (CRC), lung cancer and country of Korea, North India. Whereas, rs3746444 G allele was an increased cancer risk factor in Chinese population, especially for breast cancer. In conclusion, this meta-analysis indicated that rs2910164 C allele was associated with decreased cancer risk in Chinese population. However, the association varied from different cancer types. Furthermore, TT genotype of rs11614913 was associated with decreased cancer risk. While different cancer types and countries contributed to different effects. Whereas, rs3746444 G allele was a risk factor in Chinese population, and the association varied from different cancer types.

Polymorphisms in Interleukin-1B (IL-1B) and Interleukin 1 Receptor Antagonist (IL-1RN) Genes Associate with Gastric Cancer Risk in the Chinese Population

BackgroundGastric cancer is one of the most common malignancies afflicting the Chinese population. Polymorphisms in interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) genes have been associated with increased gastric cancer risk.AimsA case–control study enrolled 392 gastric cancer patients and 508 healthy were carried out to investigate the association between polymorphisms in IL-1B and IL-1RN and gastric cancer risk.MethodsPolymerase chain reaction (PCR)-restriction fragment length polymorphism was used for detection of two potentially functional polymorphisms (IL-1B-31 and IL-1B-511) in the IL-1B gene promoter and PCR was used for detection of the variable tandem repeat in the second intron of IL-1RN.ResultsThe data showed that the IL-1B-31CC genotype increased gastric cancer risk to an adjusted odd of 2.27 (95% CI, 1.49–3.46), IL-1B-31CT to 1.48 (95% CI, 1.01–2.16) and IL-1B-31CT/CC to 1.68 (95% CI, 1.17–2.40), while IL-1B-51TT genotype associated with increased gastric cancer risk to an adjusted odd of 2.53 (95% CI, 1.67–3.84), IL-1B-511TC to 1.45 (95% CI, 1.02–2.06), and IL-1B-511TC TT/TC to 1.72 (95% CI, 1.23, 2.39). Furthermore, IL-1RN heterogeneity genotype (IL-1RN2L) was associated with gastric cancer risk to an adjusted odd of 1.70 (95% CI, 1.05–2.74) compared to the wild-type homozygote (IL-1RNLL). In addition, H. pylori infection enhanced gastric cancer risk through these SNPs.ConclusionsThe data from the current study demonstrated that the genotype CC or CT of IL-1B-31, TT or CT of IL-1B-511, and 2L of IL-1RN increased risk of gastric cancer in this Chinese population and the risk was further enhanced by H. pylori.

Interleukin 1 beta (IL1B) promoter polymorphism and cancer risk: evidence from 47 published studies

Interleukin 1β (IL-1B) is a pro-inflammatory cytokine against infection, playing an important role in the pathogenesis of cancers. The -31T/C polymorphism of the interleukin 1β gene (IL1B) has been implicated in cancer risk through its influence on the IL1B transcription. However, results from studies are conflicting. To clarify the association, a meta-analysis was performed for 11 125 cases and 14 415 controls from 47 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. No significant associations were observed for total cancer from all the comparisons. Through the stratified analyses, there was a statistically significant decreased risk of hepatocellular cancer in carriers of the C allele than non-carriers (CC versus TT: OR = 0.87, 95% CI: 0.77-0.98, P(heterogeneity) = 0.103; TC versus TT: OR = 0.77, 95% CI: 0.62-0.95, P(heterogeneity) = 0.734; TC + CC versus TT: OR = 0.74, 95% CI: 0.61-0.91, P(heterogeneity) = 0.472). Similarly, decreased risk was observed for gastric cancer of the C/C genotype compared with the T/T genotype (OR = 0.87, 95% CI: 0.77-0.98, P(heterogeneity) = 0.103). Using the recessive model, a significantly decreased risk was observed for gastric cancer (OR = 0.88, 95% CI: 0.80-0.97, P(heterogeneity) = 0.158), European population (OR = 0.84, 95% CI: 0.73-0.97, P(heterogeneity) = 0.070) and positive infection-matched studies (OR = 0.75, 95% CI: 0.60-0.94, P(heterogeneity) = 0.220); however, an increased risk was found for breast cancer (OR = 1.34, 95% CI: 1.18-1.61, P(heterogeneity) = 0.116). Although some modest bias could not be eliminated, this meta-analysis suggests that the IL1B -31C allele is a low-penetrance protective factor for the development of cancer, in particular for that associated with infection.