LncRNA PCED1B-AS1 mediates miR-3681-3p/MAP2K7 axis to promote metastasis, invasion and EMT in gastric cancer.

BACKGROUND: LncRNA PCED1B-AS1 is abnormally expressed in multiple cancers and has been confirmed as an oncogene. Our study aimed to investigate the regulatory mechanism of lncRNA PCED1B-AS1 in gastric cancer. METHODS: TCGA database was used to analyze the abnormal expression of lncRNA PCED1B-AS1 in gastric cancer. By database prediction and mass spectrometric analysis, miR-3681-3p and MAP2K7 are potential downstream target molecules of lncRNA PCED1B-AS1 and verified by dual-luciferase report assay. RT-qPCR analysis and western blot were performed to detect the expressions of PCED1B-AS1 and MAP2K7 in gastric cancer cell lines and tissues. CCK-8 kit was applied to measure the cell viability. Wound healing and Transwell experiment were used to detect the migration and invasion. Western blot and immunohistochemical staining were performed to detect the expressions of EMT-related proteins in tissues. The changes of tumor proliferation were detected by xenograft experiment in nude mice. RESULTS: PCED1B-AS1 expression was higher but miR-3681-3 expression was lower in gastric cancer cell lines or tissues, compared to normal group. Function analysis verified PCED1B-AS1 promoted cell proliferation and inhibited cell apoptosis in gastric cancer cells in vitro and in vivo. LncRNA PCED1B-AS1 could bind directly to miR-3681-3p, and MAP2K7 was found to be a downstream target of miR-3681-3p. MiR-3681-3p mimics or si-MAP2K7 could partly reverse the effect of PCED1B-AS1 on gastric cancer cells. CONCLUSION: PCED1B-AS1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-3681-3p to upregulate MAP2K7 expression in gastric cancer, which indicated PCED1B-AS1/miR-3681-3p/MAP2K7 axis may serve as a potential therapeutic target for gastric cancer.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

m6A-related lncRNAs predict prognosis and indicate cell cycle in gastric cancer.

Background: N6-methyladenosine (m6A) modification is a common epigenetic methylation modification of RNA, which plays an important role in gastric carcinogenesis and progression by regulating long non-coding RNA (lncRNA). This study is aimed to investigate the potential prognostic signatures of m6A -related lncRNAs in STAD. Methods: The m6A-related lncRNAs with the most significant impact on gastric cancer prognosis in the TCGA database were identified by bioinformatics and machine learning methods. The m6A-related lncRNA prognostic model (m6A-LPS) and nomogram was constructed by Cox regression analysis with the minimum absolute contraction and selection operator (LASSO) algorithm. The functional enrichment analysis of m6A-related lncRNAs was also investigated. The miRTarBase, miRDB and TargetScan databases were utilized to establish a prognosis-related network of competing endogenous RNA (ceRNA) by bioinformatics methods. The correlation of AL391152.1 expressions and cell cycle were experimentally testified by qRT-PCR and flow cytometry. Results: In total, 697 lncRNAs that were identified as m6A-related lncRNAs in GC samples. The survival analysis showed that 18 lncRNAs demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of GC patients. Cox regression analysis and ROC curve indicated that this lncRNA prediction model was an independent risk factor for survival rates. Functional enrichment analysis and ceRNA network revealed that the nomogram was notably associated with cell cycle. qRT-PCR and flow cytometry revealed that downregulation of GC m6A-related lncRNA AL391152.1 could decrease cyclins expression in SGC7901 cells. Conclusion: A m6A-related lncRNAs prognostic model was established in this study, which can be applied to predict prognosis and cell cycle in gastric cancer.

No-touch endoscopic full-thickness resection technique for gastric gastrointestinal stromal tumors.

BACKGROUND : There remain concerns regarding the technical feasibility of endoscopic resection for large gastrointestinal stromal tumors (GISTs), mainly relating to the risk of tumor rupture and the adequacy of the resection margins. This study aimed to evaluate the feasibility and therapeutic outcomes of the newly developed no-touch endoscopic full-thickness resection (NT-EFTR) technique for GISTs. METHODS : In this retrospective study, 92 patients with gastric GISTs undergoing NT-EFTR were included. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS : The median tumor size was 2.5 cm and en bloc resection was achieved in all patients with negative surgical margins. The median time of the NT-EFTR procedure was 59.5 minutes. Large tumors (> 3.0 cm), extraluminal tumor growth pattern, and large gastric defects were significant contributors to long operative times. Patients were discharged within 4 days postoperatively. During follow-up, all patients were free from local recurrence and distant metastasis. CONCLUSIONS : NT-EFTR was a feasible method for the resection of gastric GISTs and can be expected to achieve complete radical resection. Large tumors with extraluminal growth and large gastric defects impact procedural difficulty.

LncRNA LINC01871 sponging miR-142-3p to modulate ZYG11B promotes the chemoresistance of colorectal cancer cells by inducing autophagy.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor in the digestive tract. Increasing evidence indicated that chemoresistance leads to a poor prognosis of CRC. Herein, we aimed to uncover the potential mechanism by which long intergenic noncoding RNA-1871 (LINC01871) affects the chemoresistance of CRC cells. METHODS: Relative level of LINC01871 in CRC tissues was assessed by reverse transcription quantitative PCR (RT-qPCR). Kaplan-Meier analysis was conducted to determine the relevance of LINC01871 and the prognosis of CRC patients. Cell Counting Kit-8 (CCK-8) and colony formation assay were used to evaluate the proliferation of SW480 cells. Expression levels of proteins and their genes were assessed by western blot, immunofluorescence staining and RT-qPCR. In addition, the interaction of LINC01871, miR-142-3p and protein zyg-11 homolog B (ZYG11B) were analyzed via dual-luciferase reporter assays. RESULTS: LINC01871 was low-expressed in CRC tissues and cell lines. Patients with a low level of LINC01871 showed significantly lower survival rate. pcDNA-LINC01871 significantly reduced the viability of SW480 cells ( P < 0.01), elevated SW480 cells sensitivity to 5-FU ( P < 0.01), reduced LC3 punctate aggregates ( P < 0.01) and downregulated the relative mRNA expression level of autophagy related protein 9A, autophagy related protein 4B and high mobility group box 1 ( P < 0.01) in SW480 cells. Moreover, LINC01871 was found to sponge miR-142-3p, and ZYG11B was the target of miR-142-3p. MiR-142-3p mimic significantly recovered the effect of pcDNA-LINC001871, whereas pcDNA-ZYG11B reversed the recovery effect of the miR-142-3p mimic. CONCLUSION: LINC01871/miR-142-3p/ ZYG11B axis regulates the chemoresistance of CRCs by inducing autophagy.

Serum IgG N-glycans enable early detection and early relapse prediction of colorectal cancer.

Colorectal cancer (CRC) develops mainly from colorectal advanced adenomas (AA), which are considered precancerous lesions. Novel early diagnostic biomarkers are urgently needed to distinguish CRC and AA from healthy control (HC). Alternative glycosylation of serum IgG has been shown to be closely associated with CRC. We aimed to explore the potential of IgG N-glycan as biomarkers in the early differential diagnosis of CRC. The study population was strictly matched to the exclusion criteria process. Serum IgG N-glycan profiles were analyzed by a robust and reliable relative quantitative method based on ultra-performance liquid chromatography (UPLC). Relative quantification and classification performance of IgG N-glycans were evaluated by Mann-Whitney U tests and ROC curve based on directly detected and derived glycan traits, respectively. Six and 14 directly detected glycan traits were significantly changed in AA and CRC, respectively, compared with HC. GP1 and GP3 were able to accurately distinguish AA from HC for early precancerous lesions screening. GP4 and GP14 provided a high value in discriminating CRC from HC. A novel combined index named GlycoF, including GP1, GP3, GP4, GP14 and CEA was developed to provide a potential early diagnostic biomarker in discriminating simultaneously AA (AUC = 0.847) and CRC (AUC = 0.844) from HC. GlycoF also demonstrated a superior CRC detection rate across CRC all stages and conspicuous prediction ability of risk of relapse. Serum IgG N-glycans analysis provided powerful early screening biomarkers that can efficiently differentiate CRC and AA from HC.

Predictors of difficult endoscopic resection of submucosal tumors originating from the muscularis propria layer at the esophagogastric junction.

BACKGROUND: Endoscopic resection approaches, including endoscopic submucosal dissection (ESD), submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (EFTR), have been widely used for the treatment of submucosal tumors (SMTs) located in the upper gastrointestinal tract. However, compared to SMTs located in the esophagus or stomach, endoscopic resection of SMTs from the esophagogastric junction (EGJ) is much more difficult because of the sharp angle and narrow lumen of the EGJ. SMTs originating from the muscularis propria (MP) in the EGJ, especially those that grow extraluminally and adhere closely to the serosa, make endoscopic resection even more difficult. AIM: To investigate the predictors of difficult endoscopic resection for SMTs from the MP layer at the EGJ. METHODS: A total of 90 patients with SMTs from the MP layer at the EGJ were included in the present study. The difficulty of endoscopic resection was defined as a long procedure time, failure of en bloc resection and intraoperative bleeding. Clinicopathological, endoscopic and follow-up data were collected and analyzed. Statistical analysis of independent risks for piecemeal resection, long operative time, and intraoperative bleeding were assessed using univariate and multivariate analyses. RESULTS: According to the location and growth pattern of the tumor, 44 patients underwent STER, 14 patients underwent EFTR, and the remaining 32 patients received a standard ESD procedure. The tumor size was 20.0 mm (range 5.0-100.0 mm). Fourty-seven out of 90 lesions (52.2%) were regularly shaped. The overall en bloc resection rate was 84.4%. The operation time was 43 min (range 16-126 min). The intraoperative bleeding rate was 18.9%. There were no adverse events that required therapeutic intervention during or after the procedures. The surgical approach had no significant correlation with en bloc resection, long operative time or intraoperative bleeding. Large tumor size (≥ 30 mm) and irregular tumor shape were independent predictors for piecemeal resection (OR: 7.346, P = 0.032 and OR: 18.004, P = 0.029, respectively), long operative time (≥ 60 min) (OR: 47.330, P = 0.000 and OR: 6.863, P = 0.034, respectively) and intraoperative bleeding (OR: 20.631, P = 0.002 and OR: 19.020, P = 0.021, respectively). CONCLUSION: Endoscopic resection is an effective treatment for SMTs in the MP layer at the EGJ. Tumors with large size and irregular shape were independent predictors for difficult endoscopic resection.

A New Preparation Method for Peroral Endoscopic Myotomy in Patients with Achalasia Can Effectively Reduce the Esophageal Residual Contents: A Comparative Retrospective Study.

METHODS: This retrospective study enrolled 65 achalasia patients who underwent POEM from June 2017 to October 2021. Based on the preoperative diet strategies, patients were divided into carbonated beverage group (n = 48) and control group (n = 17). Demographic and clinical data, duration of preoperative endoscopy, quality of esophagus cleansing, and patient satisfaction on preoperative procedure were collected and compared. In the current study, we established the quality of esophagus cleansing: Grade A, no remnants or only liquid or frothy discharge; Grade B, a little amount of solid content remained; and Grade C, a large amount of solid content remained. RESULTS: There were 41 Grade A, 6 Grade B, and 1 Grade C patients in the carbonated beverage group, while there were 8 Grade A, 6 Grade B, and 3 Grade C patients in the control group (p value = 0.001). The esophagus cleansing degrees were significantly ameliorated after drinking carbonated beverages in all the three subtypes of achalasia according to the degree of dilatation. The mean duration of preoperative endoscopy was 6.54 ± 2.250 minutes in the carbonated beverage group and 10.27 ± 4.788 minutes in the control group (p value = 0.010). The score of patient satisfaction concerning the procedure before the POEM in the carbonated beverage group was 4.5 ± 0.652, while the score in the control group was 4.35 ± 0.702 (p value = 0.436). In the multivariate analysis, patient satisfaction was significantly associated with male (odds ratio 0.296, 95% CI: 0.097-0.905, p value = 0.033). CONCLUSIONS: Drinking carbonated beverages reduce the duration of preoperative endoscopy and ameliorate the esophagus cleansing degrees without impairing patient satisfaction.

Exploration of endoscopic findings and risk factors of early gastric cancer after eradication of Helicobacter pylori.

AIM: To explore the endoscopic features and risk factors of early gastric cancer (EGC) after eradication of Helicobacter pylori (H. pylori). METHODS: A total of 1961 patients who underwent esophago-gastro-duodenoscopy (EGD) with a history of successful H. pylori eradication were enrolled in this multicenter research. Among them, 162 EGC lesions of 132 patients were detected. The endoscopic features and risk factors of post-eradication EGC were explored. RESULTS: Severe atrophy (75.3% vs. 16.7%, p value <.01), intestinal metaplasia (96.3% vs. 77.1%, p value <.01), map-like redness (89.5% vs. 65.4%, p value <.01), distinct intermediate zone (IZ) (68.5% vs. 23.4%, p value <.01) and xanthoma (58.0% vs. 17.9%, p value <.01) were significantly more frequent in the CA group (patients with newly detected EGC after eradication of H. pylori) than in the NC group (patients without gastric cancer after eradication of H. pylori). In multivariate analysis, severe atrophy (odds ratio (OR) = 8.08; 95% confidence interval (CI), 3.43-20.0; p value<.01), map-like redness (OR = 1.75; 95% CI, 0.11-5.25; p value = .04), distinct IZ (OR = 2.87; 95% CI, 1.20-6.93; p value = .02) and xanthoma (OR = 2.84; 95% CI, 1.20-7.03; p value=.02) were proved to be risk factors for detection of EGC after eradication of H. pylori. CONCLUSIONS: Severe atrophy and map-like redness and distinct IZ and xanthoma are risk factors of EGC after eradication of H. pylori.

Three novel genetic variants in NRF2 signaling pathway genes are associated with pancreatic cancer risk.

Pancreatic cancer (PanC) is one of the most lethal solid malignancies, and metastatic PanC is often present at the time of diagnosis. Although several high- and low-penetrance genes have been implicated in PanC, their roles in carcinogenesis remain only partially elucidated. Because the nuclear factor erythroid2-related factor2 (NRF2) signaling pathway is involved in human cancers, we hypothesize that genetic variants in NRF2 pathway genes are associated with PanC risk. To test this hypothesis, we assessed associations between 31 583 common single nucleotide polymorphisms (SNP) in 164 NRF2-related genes and PanC risk using three published genome-wide association study (GWAS) datasets, which included 8474 cases and 6944 controls of European descent. We also carried out expression quantitative trait loci (eQTL) analysis to assess the genotype-phenotype correlation of the identified significant SNP using publicly available data in the 1000 Genomes Project. We found that three novel SNP (ie, rs3124761, rs17458086 and rs1630747) were significantly associated with PanC risk (P = 5.17 × 10-7 , 5.61 × 10-4 and 5.52 × 10-4 , respectively). Combined analysis using the number of unfavorable genotypes (NUG) of these three SNP suggested that carriers of two to three NUG had an increased risk of PanC (P < 0.0001), compared with those carrying zero to one NUG. Furthermore, eQTL analysis showed that both rs3124761 T and rs17458086 C alleles were associated with increased mRNA expression levels of SLC2A6 and SLC2A13, respectively (P < 0.05). In conclusion, genetic variants in NRF2 pathway genes could play a role in susceptibility to PanC, and further functional exploration of the underlying molecular mechanisms is warranted.

Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) suppressed the growth of hepatocellular carcinoma cells by promoting Semaphorin 3B(SEMA3B).

AIM: Epidermal growth factor-containing fibulin-like extracellular matrix protein 1(EFEMP1) has been found to be involved in the occurrence and development of many cancers. The relationship between EFEMP1 and the development of hepatocellular carcinoma (HCC) and the molecular mechanism are not fully understood. METHODS: Real-time polymerase chain reaction (PCR) and tissue microarray were used to detect the expression of EFEMP1 in HCC cell lines and tissue. Methylation-specific PCR assay was used to measure the methylation level of EFEMP1 in HCC cell lines and tissue. To study the function of EFEMP1 on cell function, Huh7 and HepG2 were infected with lentiviral particles expressing EFEMP1. MTT assay and colony formation assay were used to examine the effect of EFEMP1 on cell proliferation. Annexin-VAPC/7-AAD double were used to detect the effect of EFEMP1 on cell apoptosis. To further detect the effect of EFEMP1 on the development of HCC in vivo, we performed the tumor formation experiment in nude mice. Gene chip was used to detect the expression profile of Huh7 and HepG2 overexpressing EFEMP1. To further screen out the differences, GO analysis and pathway analysis were performed. To study the effects of SEMA3B, specific siRNA was used to inhibit the expression of SEMA3B. Chi-squared test and rank sum test were used to analyze the relationship between EFEMP1 expression and HCC clinical characteristic. RESULTS: The study found that the expression of EFEMP1 was significantly decreased in HCC cell lines and HCC tissues. The expression level of EFEMP1 was related to the TNM (the extent of the tumor, the extent of spread to the lymph nodes, the presence of metastasis) stage and the prognosis of patients with HCC. The decrease of protein expression suggested that the patient prognosis was worse, and the protein level of EFEMP1 may be an independent factor in the prognosis of HCC patients. Promoter methylation may be one of the reasons for EFEMP1 inhibition. EFEMP1 could inhibit the proliferation of HCC cells and promoted the apoptosis of HCC cells to regulate the development of HCC. And EFEMP1 promoted the apoptosis of HCC cells mainly through the mitochondrial apoptosis pathway. EFEMP1 may inhibit the proliferation of HCC cells through the SEMA3B gene in the Axon guidance pathway. CONCLUSION: In summary, our research revealed the regulation of EFEMP1 on cell proliferation and apoptosis in HCC. EFEMP1 may suppress the growth of HCC cells by promoting SEMA3B.

Potential functional variants in SMC2 and TP53 in the AURORA pathway genes and risk of pancreatic cancer.

The AURORA pathway participates in mitosis and cell division, and alterations in mitosis and cell division can lead to carcinogenesis. Therefore, genetic variants in the AURORA pathway genes may be associated with susceptibility to pancreatic cancer. To test this hypothesis, we used three large publically available pancreatic cancer genome-wide association study (GWAS) datasets (PanScan I, II/III and PanC4) to assess the associations of 7168 single nucleotide polymorphisms (SNPs) in a set of 62 genes of this pathway with pancreatic cancer risk in 8477 cases and 6946 controls of European ancestry. We identify 15 significant pancreatic cancer risk-associated SNPs in three genes (SMC2, ARHGEF7 and TP53) after correction for multiple comparisons by a false discovery rate < 0.20. Through further linkage disequilibrium analysis, SNP functional prediction and stepwise logistic regression analysis, we focused on three SNPs: rs3818626 in SMC2, rs79447092 in ARHGEF7 and rs9895829 in TP53. We found that these three SNPs were associated with pancreatic cancer risk [odds ratio (OR) = 1.12, 95% confidence interval (CI) = 1.07-1.17 and P = 2.20E-06 for the rs3818626 C allele; OR = 0.76, CI = 0.66-0.88 and P = 1.46E-04 for the rs79447092 A allele and OR = 0.82, CI = 0.74-0.91 and P = 1.51E-04 for the rs9895829 G allele]. Their joint effect as the number of protective genotypes also showed a significant association with pancreatic cancer risk (trend test P ≤ 0.001). Finally, we performed an expression quantitative trait loci analysis and found that rs3818626 and rs9895829 were significantly associated with SMC2 and TP53 messenger RNA expression levels in 373 lymphoblastoid cell lines, respectively. In conclusion, these three representative SNPs may be potentially susceptibility loci for pancreatic cancer and warrant additional validation.

Correction: LncRNA-SVUGP2 suppresses progression of hepatocellular carcinoma.

[This corrects the article DOI: 10.18632/oncotarget.18279.].

Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk.

The platelet-derived growth factor (PDGF) signaling pathway plays important roles in development and progression of human cancers. In our study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer (PC) risk in European populations using three published genome-wide association study datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed using data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated with PC risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05-1.16, and p = 4.70 × 10-5 for the rs5757573 C allele and 1.21, 1.11-1.32, and 2.01 × 10-5 for the rs6001516 T allele]. Haplotype analysis revealed that the C-T haplotype carriers had a significantly increased risk of PC than those carrying the T-C haplotype (OR = 1.23, 95% CI = 1.12-1.34, p =5.00 × 10-6 ). The multivariate regression model incorporating the number of unfavorable genotypes (NUGs) with age and sex showed that carriers with 1-2 NUGs, particularly among 60-70 age group or males, had an increased risk of PC, compared to those without NUG. Furthermore, the eQTL analysis revealed that both loci were correlated with a decreased mRNA expression level of PDGFB in lymphoblastoid cell lines and pancreatic tumor tissues (p = 0.015 and 0.071, respectively). Our results suggest that genetic variants in PDGFB may play a role in susceptibility to PC. Further population and functional validations of our findings are warranted.

LncRNA-SVUGP2 suppresses progression of hepatocellular carcinoma.

Numerous studies indicate that long noncoding RNAs (lncRNAs) are dysregulated in hepatocellular carcinoma (HCC) and might serve as potential diagnostic biomarkers and therapeutic targets of HCC. Therefore, it is interesting to globally identify the lncRNAs altered in HCC. In our study, we used microarray to profile the levels of lncRNAs and mRNAs in three pairs of HCC and their adjacent noncancerous samples. We found lncRNA-SVUGP2, which is a splice variant of the UGP2 gene, was down-regulated in HCC samples and correlates with a better prognosis in patients with HCC. Overexpression of lncRNA-SVUGP2 in HepG2 and Hep3B liver cancer cells suppresses cell proliferation in vitro and tumor growth in vivo. Moreover, lncRNA-SVUGP2 suppresses the invasion ability of liver cancer cell lines and downregulates the mRNA and protein levels of MMP2 and 9. Additionally, lncRNA-SVUGP2 positively or negatively correlates with many mRNAs in liver cancer tissues, indicating it is multifunctional in regulating carcinogenesis.

Application of AFP whole blood one-step rapid detection kit in screening for HCC in Qidong.

Hepatocellular carcinoma (HCC) is a big problem in China where the Hepatitis B (HBV) infection patients are near to 120 million. Early screening and diagnosis is the key to reduce the incidence and mortality of HCC. Serum AFP detection is the main methods for diagnosis, recurrent monitoring and therapeutic evaluation of primary HCC. Hepatitis patients should detect the AFP at least once every six months to help early diagnosis of HCC. Unfortunately, most hepatitis and other liver disease patients do not test their AFP regularly. Therefore, a rapid, convenient detect kit for AFP is necessary for the hepatitis patients to test AFP at home by themselves. It will be very helpful to the HCC early screening and early diagnosis. We screened 859 individuals who were HBsAg positive and had high risk of HCC in Qidong by using two different kits, AFP one-step rapid detection kit (Shanghai Outdo Biotech) and AFP Diagnostics ELISA kit (Zhengzhou Autobio Diagnostics), and compared the results. As a result, the positive accordance rate and the negative accordance rate of AFP one-step rapid detection kit and the Autobio ELISA kit were 95.65% (22/23) and 99.40% (831/836), respectively. The total diagnose accordance rate reached up to 99.30% (853/859). The screening results showed a high accordance rate of two methods. It is so meaningful to achieve home-test and improve HCC early screening and diagnosis by using AFP one-step rapid detection kit.

Decreased expression of miR-193a-3p is associated with poor prognosis in colorectal cancer.

Epithelial-mesenchymal transition (EMT) is an early and key process in the metastatic cascade during the progression of colorectal cancer (CRC). The aim of the present study was to identify deregulated EMT-related microRNAs (miRNAs/miRs) of CRC and assess the effect of differentially expressed miRNAs on the prognosis of patients with CRC. Genome-wide expression profiling of miRNAs was assessed in 3 EMT-negative and 3 EMT-positive CRC tissues. Differentially expressed miRNA was further validated in 90 pairs of CRC and corresponding paracarcinoma tissues using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 6 miRNAs (miR-10a-5p miR-204-3p, miR-1224-3p, miR-193a-3p, miR-365a-3p and miR-3678-3p) were identified to be differentially expressed between different EMT statuses of CRC tissues. Following validation using RT-qPCR, 3 miRNAs (miR-10a-5p, miR-365a-3p and miR-193a-3p) were selected for subsequent studies. The expression levels of miR-10a-5p, miR-193a-3p and miR-365a-3p were markedly increased compared with levels in corresponding paracarcinoma tissues. Survival analyses revealed that down-regulation of miR-193a-3p was associated with worse prognosis of patients with CRC, particularly in female and older patients. The results of the present study indicate that miR-193a-3p may be an EMT-related biomarker and serve as a novel prognostic factor for CRC.

miRNA-338-3p/CDK4 signaling pathway suppressed hepatic stellate cell activation and proliferation.

BACKGROUND: Activated hepatic stellate cell (HSC) is the main fibrogenic cell type in the injured liver. miRNA plays an important role in activation and proliferation of HSC. METHODS: Our previous study examined the expression profiles of microRNAs in quiescent and activated HSC. Real-time PCR and western blot were used to detect the expression of Collagen type I (Col 1) and Alpha-Smooth Muscle Actin (α-SMA). CCK-8 and Edu assay was used to measure the proliferation rate of HSC. Luciferase reporter gene assay was used to tested the binding between miR-338-3p and Cyclin-dependent kinase 4 (CDK4). RESULTS: We found overexpression of miR-338-3p could inhibit Col 1 and α-SMA, two major HSC activation markers, whereas miR-338-3p inhibitor could promote them. Besides, miR-338-3p overexpression could suppress the growth rate of HSC. Further, we found that CDK4, a pleiotropic signaling protein, was a direct target gene of miR-338-3p. Moreover, we found that overexpression of CDK4 could block the effects of miR-338-3p. CONCLUSIONS: We found miR-338-3p is an anti-fibrotic miRNA which inhibits cell activation and proliferation. Our findings suggest that miR-338-3p/CDK4 signaling pathway participates in the regulation of HSC activation and growth and may act as a novel target for further anti-fibrotic therapy.

HOTAIR is a predictive and prognostic biomarker for patients with advanced gastric adenocarcinoma receiving fluorouracil and platinum combination chemotherapy.

Accumulating evidence suggests that long non-coding RNA (lncRNA) HOTAIR participates in many types of cancer such as gastric cancer and may confer malignant phenotype to tumor cells. Fluorouracil and platinum combination chemotherapy is the first line therapy for gastric cancer. However, it is still unknown whether HOTAIR influences the outcome of cancer patients treated with chemotherapy. This study aimed to evaluate the association of HOTAIR expression with the prognosis of patients with advanced gastric adenocarcinoma (GA) receiving fluorouracil and platinum based chemotherapy. We examined the levels of HOTAIR in 168 GA samples using quantitative real-time PCR and analyzed its relationship with clinical features and prognosis of patients with advanced GA treated with fluorouracil and platinum based chemotherapy. Compared with paracancerous tissues, HOTAIR was significantly upregulated in GA tissues, especially in more advanced cases. High HOTAIR expression was an independent poor prognostic factor for patients with advanced GA. Further stratification analyses revealed that the association between HOTAIR expression and survival in patients with advanced GA remained significant in the subgroup of patients with TNM stages IIIA and IIIB, poorly differentiated, and smaller tumors. In conclusion, our results provide first evidence that HOTAIR may be served as a biomarker that predicts which patient with advanced GA will benefit from fluorouracil and platinum combination chemotherapy.