RNA-sequencing reveals the expression profiles of tsRNAs and their potential carcinogenic role in cholangiocarcinoma.

BACKGROUND: Recently, the incidence of cholangiocarcinoma (CCA) has gradually increased. As CCA has a poor prognosis, the ideal survival rate is scarce for patients. The abnormal expressed tsRNAs may regulate the progression of a variety of tumors, and tsRNAs is expected to become a new diagnostic biomarker of cancer. However, the expression of tsRNAs is obscure and should be elucidated in CCA. METHODS: High-throughput RNA sequencing technology (RNA-seq) was utilized to determine the overall expression profiles of tsRNAs in three pairs CCA and adjacent normal tissues and to screen the tsRNAs that were differentially expressed. The target genes of dysregulated tsRNAs were predicted and the biological effects and potential signaling pathways of these target genes were explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate 11 differentially expressed tRFs with 12 pairs CCA and adjacent normal tissues. RESULTS: High-throughput RNA-seq totally demonstrated 535 dysregulated tsRNAs, of which 241 tsRNAs were upregulated, such as tRF-21-YLKZKWE5D，tRF-16-9NF5W8B，tRF-27-78YLKZKWE52，tRF-19-RLXN48KP，tRF-33-IK9NJ4S2I7L7DV，tRF-19-F8DHXYIV, and 294 tsRNAs were downregulated (tRF-20-739P8WQ0, tRF-34-JJ6RRNLIK898HR, tRF-17-VL8RPY5, tRF-23-YP9LON4VDP, tRF-39-EH623K76IR3DR2I2, tRF-17-18YKISM, tRF-19-Q1Q89PJZ, etc.) in CCA compared with adjacent normal tissues (|log2 [fold change] | ≥ 1 and p value <0.05). GO and KEGG enrichment analyses indicated that the target genes of dysregulated tRFs (tRF-34-JJ6RRNLIK898HR, tRF-38-0668K87SERM492V, and tRF-39-0668K87SERM492E2) were mainly enriched in the Notch signaling pathway, Hippo signaling pathway, cAMP signaling pathway and in growth hormone synthesis, secretion and action, etc. qRT-PCR result showed that tRF-34-JJ6RRNLIK898HR/tRF-38-0668K87SERM492V/tRF-39-0668K87SERM492E2 was downregulated (p = 0.021), and tRF-20-LE2WMK81 was upregulated in CCA (p = 0.033). CONCLUSION: Differentially expressed tRFs in CCA are enriched in many pathways associated with neoplasms, which may impact the tumor progression and have potential to be diagnostic biomarkers and therapeutic targets of CCA.

Interaction of HULC polymorphisms with Helicobacter pylori infection plays a strong role for the prediction of gastric cancer risk.

Aim: Gene-environment interactions have better efficacy in predicting cancer susceptibility than a single gene. Materials & methods: Eight tag single nucleotide polymorphisms encompassing the whole HULC gene were detected by KASP platform (LGC Genomics, Hoddesdon, UK) in 631 gastric cancer (GC) cases and 953 controls. Results: The HULC gene rs7770772 polymorphism could increase GC risk (recessive model: odds ratio = 1.95). The multifactor dimensionality reduction (MDR) analysis suggested that the 2D model HULC rs7770772-Helicobacter pylori had better effect on GC risk prediction (maximum testing accuracy = 0.7005). No significant result was observed in our experimental expression quantitative trait loci analysis. Conclusion: 2D model HULC rs7770772-H. pylori might have superior efficacy for GC risk than a single factor.

MetaDE-Based Analysis of circRNA Expression Profiles Involved in Gastric Cancer.

BACKGROUND: Circular RNAs (circRNAs) could play carcinogenic roles in gastric cancer (GC) and have potential to be biomarkers for GC early diagnosis, which needs to be further excavated and supported by more evidence. AIMS: The study aims to identify more authentic circRNA expression profiles that could function as potential biomarkers in GC. METHODS: circRNA expression data in three microarrays were downloaded from Gene Expression Omnibus datasets. A systematic meta-analysis based on an integrated dataset pre-processed from the three microarrays was conducted to identify a panel of differentially expressed circRNAs (DEcircs) by using the metaDE package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term enrichment were used to note the corresponding functions of DEcircs. Quantitative real-time polymerase chain reaction was applied to verify the DEcircs expression in cancer tissues and adjacent paracancerous tissues. A GC risk-related circRNAs-miRNAs-mRNAs network was further constructed and analyzed. RESULTS: MetaDE analysis suggested 64 DEcircs between cancer tissues and adjacent normal tissues. GO and KEGG analysis showed that the parental genes of these DEcircs were mainly associated with histone methylation, Wnt signalosome and histone methylation activity. Hsa_circ_0005927 and hsa_circ_0067934 were verified in GC tissues, and a GC risk-related network was constructed. CONCLUSION: MetaDE-based circRNA expression profiles revealed a series of potential biomarkers involved in GC. Two circRNAs, hsa_circ_0005927 and hsa_circ_0067934, could be more authentic biomarkers for GC screening. The GC risk-related network of hsa_circ_0005927/hsa_circ_0067934 and their downstream targets will provide new genetic insights for GC research.

MicroRNA-200b suppresses the invasion and migration of hepatocellular carcinoma by downregulating RhoA and circRNA_000839.

MicroRNAs could mediate the targeted coding gene and the targeted non-coding RNA to form endogenous competition, which have an important regulatory role in tumorigenesis of many types of cancer, including hepatocellular carcinoma. The goal of this study was to characterize the role of miR-200b in the pathogenesis of hepatocellular carcinoma. We identified miR-200b that was predicted to regulate RhoA and circ_000839. Our data establish that miR-200b is expressed at a relatively low level in hepatocellular carcinoma ( p < 0.001). RhoA and circ_000839 are expressed at a relatively high level in hepatocellular carcinoma ( p < 0.001, respectively). Our mechanistic data indicate that RhoA is a direct target of miR-200b ( p < 0.001), binding of which affects the expression of invasion and migration in hepatocellular carcinoma cell lines ( p < 0.05). And correlation analysis showed that miR-200b was inversely correlated with RhoA and circ_000839 ( p = 0.012, p = 0.002, respectively), while RhoA was positively correlated with circ_000839 ( p < 0.001). Taken together, our data suggest that miR-200b could mediate RhoA gene and circ_000839 to form endogenous competition. And this is a direction for the association study of miR-200b and RhoA in the future.

Interactions among polymorphisms of NER genes prompt the risk of transplantation rejection.

Better efficacy for predicting the risk of transplantation rejection could be achieved by intergenic interactions among single nucleotide polymorphisms (SNPs) compared with one SNP. In this study, we explored the forewarning function of interactions among SNPs in nucleotide excision repair (NER) genes. Thirty-eight polymorphisms in eight NER genes were genotyped by Sequenom MassARRAY platform, including XPA, XPC, DDB2, XPB (ERCC3), XPD (ERCC2), ERCC1, XPF (ERCC4), and XPG (ERCC5). The haplotype analysis suggested that XPA rs3176629-rs2808668 C-T and ERCC5 G-C-C-T and G-C-T-C (OR = 1.81, 7.72 and 3.46, respectively) increased the risk of transplantation rejection; while ERCC5 rs2094258-rs751402-rs2296147-rs1047768 A-C-T-T decreased the risk (OR = 0.35). Multiple logistic regression and multifactor dimensionality reduction (DMR) analyses consistently revealed intergenic interactions among ERCC2 rs50871, ERCC5 rs1047768, and XPC rs2228001 SNPs for the risk of transplantation rejection. Taken together, the interactions among XPC rs2228001, ERCC2 rs50871 and ERCC5 rs1047768 SNPs were associated with the risk of transplantation rejection.

TLR3 gene polymorphisms in cancer: a systematic review and meta-analysis.

INTRODUCTION: Recent studies examining the association of Toll-like receptor 3 (TLR3) gene polymorphisms with the risk of developing various types of cancer have reported conflicting results. Clarifying this association could advance our knowledge of the influence of TLR3 single nucleotide polymorphisms (SNPs) on cancer risk. METHODS: We systematically reviewed studies that focused on a collection of 12 SNPs located in the TLR3 gene and the details by which these SNPs influenced cancer risk. Additionally, 14 case-control studies comprising a total of 7997 cases of cancer and 8699 controls were included in a meta-analysis of 4 highly studied SNPs (rs3775290, rs3775291, rs3775292, and rs5743312). RESULTS: The variant TLR3 genotype rs5743312 (C9948T, intron 3, C>T) was significantly associated with an increased cancer risk as compared with the wild-type allele (odds ratio [OR]=1.11, 95% confidence interval [CI]=1.00-1.24, P=0.047). No such association was observed with other TLR3 SNPs. In the stratified analysis, the rs3775290 (C13766T, C>T) variant genotype was found to be significantly associated with an increased cancer risk in Asian populations. Additionally, the rs3775291 (G13909A, G>A) variant genotype was significantly associated with an increased cancer risk in Asians, subgroup with hospital-based controls, and subgroup with a small sample size. CONCLUSION: After data integration, our findings suggest that the TLR3 rs5743312 polymorphism may contribute to an increased cancer risk.

Pri-miR-34b/c rs4938723 TC heterozygote is associated with increased cancer risks: evidence from published data.

The promoter region of the microRNA pri-miR-34b/c has a potentially functional polymorphism, rs4938723, located in a typical CpG island. Studies of the association between pri-miR-34b/c rs4938723 polymorphism and risks of various cancers have had inconsistent results. We therefore conducted a meta-analysis of nine studies that included 6,036 cancer patients and 7,490 controls to address this association. Overall, this meta-analysis showed the pri-miR-34b/c rs4938723 TC heterozygote to be significantly associated with increased risk of overall cancers compared with the wild-type TT genotype (P = 0.010, odds ratio (OR) = 1.10, 95 % confidence interval (CI) 1.02-1.18). In stratified analysis, the TC heterozygote was significantly associated with increased cancers risks in digestive tract cancers, in hepatocellular cancer, in Asian population and in the large-sample subgroup. The CC genotypes of rs4938723 were also associated with increased hepatocellular cancer risk but associated with decreased colorectal cancer risk in the stratification analysis by a single cancer type. Thus our meta-analysis suggests that the pri-miR-34b/c rs4938723 TC heterozygote contributes to increased overall cancer risks, as well as shown in digestive tract cancers, in hepatocellular cancer, in Asian population and in the large-sample subgroup. This rs4938723 SNP showed an opposite tendency orientation between the hepatocellular cancer and colorectal cancer risks. Large-sample studies are needed to verify our findings.

A bibliometric analysis of immune-related adverse events in cancer patients and a meta-analysis of immune-related adverse events in patients with hepatocellular carcinoma.

Background and Objectives: Immunotherapy has become the standard treatment for hepatocellular carcinoma (HCC), but it carries a risk of immune-related adverse events (irAEs) that can be life-threatening. This study employs bibliometric analysis to understand global scientific research on irAEs in cancer, focusing on characteristics and areas of interest. Additionally, a meta-analysis provides a comprehensive overview of irAEs in HCC patients receiving immune checkpoint inhibitor (ICI)-based therapies. Methods: We conducted a thorough search of Web of Science Core Collection (WoSCC) publications from 1999 to 2022. R and VOSviewer software were used for analysis. A meta-analysis was performed using data from PubMed, Embase, and the Cochrane Library databases up to March 22, 2022. Trials with HCC patients reporting irAE incidence were included. Quality assessment followed Cochrane risk of bias, Newcastle-Ottawa Scale (NOS), and Methodological Index for Non-Randomized Studies (MINORS). We used random-effects or fixed-effects models based on I2 values. Primary outcomes included any-grade irAEs and grade ≥ 3 irAEs. This review and meta-analysis are registered in PROSPERO as CRD42022318885. Results: In bibliometric analysis, we included 2946 papers, showing a consistent rise in annual publications on irAEs in cancer research. Frequent keywords were "nivolumab", "immune checkpoint inhibitor", and "immune-related adverse event". "Hepatocellular carcinoma" emerged as a prominent research focus linked to irAEs. We conducted a comprehensive meta-analysis on irAE incidence in HCC patients, including 29 studies. The overall incidence of any-grade irAEs was 61.0% (95% CI 38.5%-81.3%), and grade ≥ 3 irAEs was 13.2% (95% CI 7.9%-19.6%). Treatment-related mortality occurred in 3.1% (95% CI 0.8%-6.3%), with treatment discontinuation at 10.7% (95% CI 6.3%-16.0%). Reactive cutaneous capillary endothelial proliferation (RCCEP) was the most common any-grade irAE, while elevated aspartate aminotransferase (AST) was the most common grade ≥ 3 irAE. Treatment strategies were independently associated with specific irAEs, as indicated by multivariable analysis. Conclusion: This study provides valuable insights into the current research landscape of irAEs in cancer and ofers a comprehensive overview of irAEs in HCC patients undergoing ICI-based therapy. The relatively high incidence of irAEs and their association with treatment strategies emphasize the need for careful management by clinicians when treating HCC patients. These findings offer significant guidance for optimizing care and treatment for HCC patients.

Mendelian randomization reveals potential causal relationships between cellular senescence-related genes and multiple cancer risks.

Cellular senescence is widely acknowledged as having strong associations with cancer. However, the intricate relationships between cellular senescence-related (CSR) genes and cancer risk remain poorly explored, with insights on causality remaining elusive. In this study, Mendelian Randomization (MR) analyses were used to draw causal inferences from 866 CSR genes as exposures and summary statistics for 18 common cancers as outcomes. We focused on genetic variants affecting gene expression, DNA methylation, and protein expression quantitative trait loci (cis-eQTL, cis-mQTL, and cis-pQTL, respectively), which were strongly linked to CSR genes alterations. Variants were selected as instrumental variables (IVs) and analyzed for causality with cancer using both summary-data-based MR (SMR) and two-sample MR (TSMR) approaches. Bayesian colocalization was used to unravel potential regulatory mechanisms underpinning risk variants in cancer, and further validate the robustness of MR results. We identified five CSR genes (CNOT6, DNMT3B, MAP2K1, TBPL1, and SREBF1), 18 DNA methylation genes, and LAYN protein expression which were all causally associated with different cancer types. Beyond causality, a comprehensive analysis of gene function, pathways, and druggability values was also conducted. These findings provide a robust foundation for unravelling CSR genes molecular mechanisms and promoting clinical drug development for cancer.

The co-expression of functional gastric proteins in dynamic gastric diseases and its clinical significance.

BACKGROUND: Pepsinogen C (PGC) and mucin1 (MUC1) are important physiologically functional gastric proteins; Mucin2 (MUC2) is an "ectopic" functional protein in intestinal metaplasia of gastric mucosa. We analyzed the co-expression of the above-mentioned three proteins in dynamic gastric diseases {superficial gastritis (SG)-atrophic gastritis (AG)--gastric cancer (GC)} as well as different histological types of gastric cancer in order to find molecular phenotypes of gastric cancer and precancerous disease and further explore the potential co-function of PGC, MUC1 and MUC2 in the occurrence and development of gastric cancer. METHODS: The SG-AG-GC sequence was 57-57-70 cases in this case-control study, respectively. Different histological types of GC were 28 cases of highly and moderately differentiated aden ocarcinoma (HMDA)、30 of poorly differentiated adenocarcinoma (PDA) and 12 of mucinous adenocarcinoma (MA) or signet ring cell carcinoma (SRCC). PGC, MUC1 and MUC2 expression in situ were detected in all 184 cases using immunohistochemistry. RESULTS: Both PGC and MUC1 had a significantly decreased expression in GC than in SG and AG (P < 0.0001 and P < 0.01, respectively); While MUC2 had a significant increased expression in AG than in SG and GC (P < 0.0001). Seven phenotypes of PGC, MUC1 and MUC2 co-expression were found in which PGC+/MUC1+/MUC2- phenotype took 94.7%(54/57) in SG group; PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+ phenotype took 43.9% (25/57) and 52.6% (30/57) in AG; the phenotypes in GC group appeared variable; extraordinarily, PGC-/MUC1-/MUC2+ phenotype took 100% (6/6) in MA or SRCC group and had a statistical significance compared with others (P < 0.05). CONCLUSIONS: Phenotypes of PGC, MUC1 and MUC2 co-expression in dynamic gastric diseases are variable. In SG group it always showed PGC+/MUC1+/MUC2- phenotype and AG group showed two phenotypes (PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+); the phenotypes in GC group appeared variable but the phenotype of PGC-/MUC1-/MUC2+ may be a predictive biomarker for diagnosing MA or SRCC, or distinguishing histological MA or SRCC from tubular adenocarcinoma accompanied by mucinous secretion or signet ring cell scattered distribution.

Non-coding RNA and hepatitis B virus-related hepatocellular carcinoma: A bibliometric analysis and systematic review.

Objectives: A bibliometric analysis for non-coding RNA and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) was performed to describe international research status and visualize the research scope and emerging trends over the last two decades on this topic. Materials and methods: Research data of non-coding RNA and HBV-related HCC were retrieved and extracted from the Web of Science Core Collection (WoSCC) database from 1 January 2003 to 13 June 2022 and then analyzed by means of bibliometric methods. A total of 1,036 articles published in this field were assessed for specific characteristics, including the year of publication, journal, author, institution, country/region, references, and keywords. VOSviewer was employed to perform co-authorship, co-occurrence, and co-citation analyses accompanied by constructing a visual network. Results: Overall, 1,036 reports on non-coding RNA and HBV-related HCC from 2003 to 2022 were retrieved from WoSCC. The publication has gradually increased during the last two decades with 324 journals involved. Most research records (748 publications and 23,184 citations) were concentrated in China. A co-occurrence cluster analysis for the top 100 keywords was performed and four clusters were generated: (1) non-coding RNA as a molecular marker for the diagnosis and prognosis of HBV-related HCC; (2) dysregulation of non-coding RNA by hepatitis B virus X protein (HBx); (3) non-coding RNA affecting the biological behaviors of HBV-related HCC; and (4) epidemiological study for the effects of non-coding RNA on the risk of HBV-related HCC. Conclusion: The publications and citations involved in non-coding RNA and HBV-related HCC have increased over the last two decades associated with many countries, institutions, and authors. Our study revealed current development trends, global cooperation models, basic knowledge, research hotspots, and emerging frontiers in this field.

Predicting Prognosis of Hepatocellular Carcinoma Patients Based on the Expression Signatures of Mitophagy Genes.

Background: The unbalance of mitophagy was closely related to hepatocellular carcinoma (HCC) progression. At present, it has not been uncovered about the influence of mitophagy genes on HCC prognosis and their potential pathogenesis. Materials and Methods: The expression and clinical information of HCC in TCGA cohort were used to identify mitophagy differentially expressed genes (MDEGs) with prognostic value. The prognostic model of mitophagy genes was built and externally validated by LASSO regression in TCGA cohort and ICGC cohort, respectively. The function of the prognostic signature and its association with immune cell infiltration were explored. The profile of MDEGs was validated with 39 pairs HCC and paracarcinoma tissues by quantitative reverse transcription-PCR (qRT-PCR). Results: A total of 18 mitophagy genes that were upregulated and contributed to poor prognosis in HCC were identified. These genes could interact with each other. The correlation analysis showed that there was positively correlation among mitophagy genes. According to optimal λ value, 8 mitophagy gene signatures were involved in prognostic model. Based on median risk scores, HCC patients were divided into high-risk group and low-risk group. Compared with the low-risk group, the high-risk group has worse overall survival in TCGA cohort and ICGC cohort. The univariate and multivariate Cox regression analysis suggested that risk score was an independent prognostic factor of HCC patients. Time-dependent ROC curve was used to identify and validate good predicting performance of the prognostic model. Enrichment analysis showed that risk differentially expressed genes were enriched in various metabolism and cell division processes. The immune cell infiltration score and immune function were significantly different in two groups. qRT-PCR validation result showed that QSTM1, CSNK2B, PGAM5, and ATG5 were upregulated. Conclusion: Mitophagy genes could influence HCC progression through regulating the metabolism and immune functions and could be used to predict prognosis and considered as potential prognostic biomarker and precise therapeutic target of HCC.

Pan-cancer analysis of forkhead box Q1 as a potential prognostic and immunological biomarker.

Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family involved in the occurrence and development of different tumors. However, the specific expression patterns and functions of FOXQ1 in pan-cancer remain unclear. Therefore, we collected the expression, mutation, and clinical information data of 33 tumors from The Cancer Genome Atlas database. Via public pan-cancer transcriptome data analysis, we found that FOXQ1 is differentially expressed in various tumors at tissue and cell levels, such as liver hepatocellular carcinoma, colon adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, thyroid carcinoma, and kidney renal clear cell carcinoma. Kaplan-Meier and Cox analyses suggested that FOXQ1 expression was associated with poor overall survival of cutaneous melanoma and thymoma. Its expression was also associated with good disease-specific survival (DSS) in prostate adenocarcinoma but poor DSS in liver hepatocellular carcinoma. In addition, FOXQ1 expression was associated with poor disease-free survival of pancreatic adenocarcinoma. Moreover, FOXQ1 expression was closely related to the tumor mutational burden in 14 tumor types and microsatellite instability (MSI) in 8 tumor types. With an increase in stromal and immune cells, FOXQ1 expression was increased in breast invasive carcinoma, pancreatic adenocarcinoma, thyroid carcinoma, lung adenocarcinoma, and ovarian serous cystadenocarcinoma, while its expression was decreased in pancreatic adenocarcinoma, bladder urothelial carcinoma, and stomach adenocarcinoma. We also found that FOXQ1 expression was related to the infiltration of 22 immune cell types in different tumors (p < 0.05), such as resting mast cells and resting memory CD4 T cells. Last, FOXQ1 was coexpressed with 47 immune-related genes in pan-cancer (p < 0.05). In conclusion, FOXQ1 expression is closely related to prognosis, clinicopathological parameters, cancer-related pathway activity, the tumor mutational burden, MSI, the tumor microenvironment, immune cell infiltration, and immune-related genes and has the potential to be a diagnostic and prognostic biomarker as well as an immunotherapy target for tumors. Our findings provide important clues for further mechanistic research into FOXQ1.

The role of non-coding RNA in the diagnosis and treatment of Helicobacter pylori-related gastric cancer, with a focus on inflammation and immune response.

Helicobacter pylori (H. pylori) is one of the globally recognized causative factors of gastric cancer (GC). Currently, no definite therapy and drugs for H. pylori-related GC have been widely acknowledged although H. pylori infection could be eradicated in early stage. Inflammation and immune response are spontaneous essential stages during H. pylori infection. H pylori may mediate immune escape by affecting inflammation and immune response, leading to gastric carcinogenesis. As an important component of transcriptome, non-coding RNAs (ncRNAs) have been proven to play crucial roles in the genesis and development of H. pylori-induced GC. This review briefly described the effects of ncRNAs on H. pylori-related GC from the perspective of inflammation and immune response, as well as their association with inflammatory reaction and immune microenvironment. We aim to explore the potential of ncRNAs as markers for the early diagnosis, prognosis, and treatment of H. pylori-related GC. The ncRNAs involved in H. pylori-related GC may all hold promise as novel therapeutic targets for immunotherapy.

Interferon-alpha responsible EPN3 regulates hepatitis B virus replication.

Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane protein epsin3 (EPN3) negatively regulates the expression of HBV RNA. EPN3 expression was induced by transfection of an HBV replicon plasmid, and reduced HBV-RNA level in hepatic cell lines and murine livers hydrodynamically injected with the HBV replicon plasmid. Viral RNA reduction by EPN3 was dependent on transcription, and independent from epsilon structure of viral RNA. Viral RNA reduction by overexpression of p53 or IFN-α treatment, was attenuated by knockdown of EPN3, suggesting its role downstream of IFN-α and p53. Taken together, this study demonstrates the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed.

The role of Transfer RNA-Derived Small RNAs (tsRNAs) in Digestive System Tumors.

Transfer RNA-derived small RNA(tsRNA) is a type of non-coding tRNA undergoing cleavage by specific nucleases such as Dicer. TsRNAs comprise of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Based on the splicing site within the tRNA, tRFs can be classified into tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF. TiRNAs can be classified into 5'-tiRNA and 3'-tiRNA. Both tRFs and tiRNAs have important roles in carcinogenesis, especially cancer of digestive system. TRFs and tiRNAs can promote cell proliferation and cell cycle progression by regulating the expression of oncogenes, combining with RNA binding proteins such as Y-box binding protein 1 (YBX1) to prevent transcription. Despite many reviews on the basic biological function of tRFs and tiRNAs, few have described their correlation with tumors especially gastrointestinal tumor. This review focused on the relationship of tRFs and tiRNAs with the biological behavior, clinicopathological characteristics, diagnosis, treatment and prognosis of digestive system tumors, and would provide novel insights for the early detection and treatment of digestive system tumors.

HOTTIP polymorphism may affect gastric cancer susceptibility by altering HOTTIP expression.

BACKGROUND: Non-coding RNA polymorphisms can affect disease risk and prognosis by influencing gene expression. Here, we first investigated the association between single nucleotide polymorphisms (SNPs) of long non-coding RNA (lncRNA) HOTTIP and gastric cancer risk/prognosis. METHODS: A total of five HOTTIP SNPs among 627 gastric cancer cases and 935 controls were tested by Kompetitive Allele Specific PCR (KASP) assay. The functional SNPs underwent eQTL analysis and the expression of HOTTIP was assessed by quantitative RT-PCR. RESULTS: The rs2067087 and rs3807598 SNPs of HOTTIP increased susceptibility to gastric cancer (rs2067087: dominant model, P=0.008, odds ratio (OR) = 1.35; rs3807598: recessive model, P=0.037, OR = 1.29). Both HOTTIP rs2067087 and rs3807598 could affect the expression of mature lncRNA (P=0.003 and P=0.032, respectively). CONCLUSION: The rs2067087 and rs3807598 SNPs of HOTTIP are associated with gastric cancer risk, possibly by affecting the expression of mature HOTTIP.

[The effect of iNOS gene expression inhibited by RNA inference on the pancreas islet apoptosis and function in rats].

OBJECTIVE: To investigate the effect of iNOS gene on cell apoptosis and insulin secretion of pancreas islet in rats by RNA inference (RNAi). METHODS: Islets obtained from thirty Wistar rats were randomly divided into five groups, and siRNA oligo was purchased from Genepharma in Shanghai. The cultured islets were transfected with iNOS siRNA, and then were divided into five groups. Islet cultured only was taken as blank control group, and cultured with TNF-alpha + IL-1 beta as cytokine group. Islet transfected with negative or iNOS siRNA were taken as negative transfection control group or RNAi group, while that transfected with iNOS siRNA and cultured with TNF-alpha + IL-1 beta as RNAi + cytokine group. Expression of iNOS mRNA was evaluated by RT-PCR and iNOS protein was evaluated by Western blot to detect the effect of RNAi. The expression of apoptosis correlated gene, Bax, Fas were analyzed, and the apoptotic cells were identified by TUNEL method meanwhile. Insulin secretion index assay the function of the islets. RESULTS: 500 - 600 IEQ islets could be extracted from every rat. RNAi attenuated the expression of iNOS and restrained the synthesis of iNOS protein.With treatment of cytokines IL-1 beta and TNF-alpha, the level of iNOS increased remarkably, the expression of Bax and Fas ascended distinctly, and insulin secretion index decreased strikingly. While, the expression of apoptosis gene and amount of apoptotic cells descended in group of RNAi + cytokine, and insulin secretion index were satisfying. CONCLUSION: The apoptosis from cytokines to islets mediated by iNOS could be suppressed by RNAi, which leaded to favorable function and survival of islets.

Savitzky-Golay filter based contrast-enhanced ultrasound quantification in hepatic tumors: Methodology and its correlation with tumor angiogenesis.

BACKGROUND: Savitzky-Golay filter is a digital filter used in data smoothing, we introduced a contrast-enhanced ultrasound (CEUS) quantification software based on the filter (SGCQ). OBJECTIVE: To explore the methodology of analyzing hepatic tumors hemodynamics applying SGCQ software and the correlation between SGCQ parameters and hepatocellular carcinoma (HCC) angiogenesis. METHODS: Nighty-seven right-lobe located hepatic mass cases (15 females and 82 males, mean age 58±10y, mean lesion size: 39.9±11.6 mm) underwent CEUS scan preoperatively and had a final diagnosis of HCC (n = 52) or colorectal cancer metastatic liver tumors (MLT, n = 45) were included. CEUS was carried out using a 1-5 MHz convex probe. The CEUS clips were recorded and analyzed off-line to obtain the parameters. The parameters were analyzed by 3 observers separately to investigate inter-observer variability. Parameters were compared between tumor and adjacent liver and between different tumors. Immunohistochemistry was used to evaluate the microvessel density (MVD) of HCC, and the correlation between the parameters and MVD was analyzed. RESULTS: Intraclass correlation coefficient (ICC) of all parameters were greater than 0.75 except wash-in slope (a3) and time to peak (TTP) of adjacent liver. The parameters of a3, wash-out slope (a2), perfusion time (PT) and area under the curve (AUC) were significantly different between HCC and liver. The a2, a3, AUC, PT and enhanced intensity (EI) were significantly different between MLT and liver. AUC, a2, a3, da1 and dPI were significantly different between HCC and MLT. AUC, a2 and EI correlated with MVD. CONCLUSION: SGCQ software quantification have good consistency among three observers, the parameters of SGCQ can display the hemodynamics of HCC and MLT and the difference between them. AUC and EI can serve as useful biomarkers in tumor angiogenesis evaluation.

lncRNA-PCAT1 rs2632159 polymorphism could be a biomarker for colorectal cancer susceptibility.

Background: Single-nucleotide polymorphisms (SNPs) in lncRNAs could be biomarkers for susceptibility to colorectal cancer (CRC), but the association of PCAT1 polymorphisms and CRC susceptibility is yet to be studied. Methods: Five tagSNPs covering the PCAT1 gene were detected through Kompetitive Allele-Specific PCR among 436 CRC patients and 510 controls. An expression quantitative trait locus (eQTL) bioinformatic analysis was then performed. Results: In the present study, PCAT1 rs2632159 polymorphism increased CRC risk by 1.37-fold and 2.19-fold in the dominant and recessive models, respectively (P=0.040 and 0.041). When the CRC cases were divided into colon cancer and rectal cancer, we found that this polymorphism affected colon cancer risk under the dominant model (P=0.022, OR = 1.51) and affected rectal cancer susceptibility under the recessive model (P=0.009, OR = 3.03). A more pronounced effect was observed in the male subgroup in that PCAT1 rs2632159 SNP increased rectal cancer risk by 3.97-fold (P=0.017). When PCAT1 rs2632159 was present, epistatic effects were observed with rs1902432 and rs785005 (P=0.011 and 0.008, respectively). eQTL analysis showed that rs2632159 could influence binding with the transcription factors EBF, LUN-1, and TCF12. Conclusion:PCAT1 rs2632159 SNP could be a biomarker for CRC risk. And the rs1902432 SNP might only have potential to be a biomarker for colon cancer risk.