IncRNA MIAT Accelerates Keloid Formation by miR-411-5p/JAG1 Axis.

The long non-coding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) regulates the biological functions of many kinds of cells. The aim of this study is to explore the mechanism of MIAT and how it affects keloid progression. The expressions of MIAT, JAG1, and miR-411-5p in keloid tissues and keloid fibroblasts (KEL FIBs) were quantified by conducting Western blot and quantitative reverse transcription polymerase chain reaction analyses. The influences of MIAT, JAG1, and miR-411-5p on the abilities of KEL FIBs to proliferate, migrate, and invade were assessed by means of the CCK-8, wound healing, and Transwell experiments. To determine the binding relationship among MIAT, JAG1, and miR-411-5p, we performed luciferase reporter and RIP experiments. In keloid tissues and KEL FIBs, MIAT and JAG1 were upregulated while miR-411-5p was downregulated. Knocking-down MIAT or JAG1 significantly inhibited proliferation, migration and invasion. On the contrary, suppressing miR-411-5p expression produced an opposite effect. With regard to mechanisms, MIAT sponged miR-411-5p, which targeted JAG1. MIAT accelerates keloid formation by modulating the miR-411-5p/JAG1 axis.

miR-548a-3p Weakens the Tumorigenesis of Colon Cancer Through Targeting TPX2.

Background: MicroRNA (miRNA) has been verified a significant factor to participate in the progression of colon cancer (CC). In this study, the authors investigated the mechanism and function of miR-548a-3p in CC. Materials and Methods: Bioinformatics analysis was used to analyze the mRNA expression profile and miRNA expression profile from GEO data series. The expression of miRNA and mRNA was analyzed by real-time quantification polymerase chain reaction in 43 pairs of CC clinical tissue samples and CC cells. The Western blot assay was used to detect the TPX2 protein. Then, SW480 and HCT116 cells were stably transfected with miR-548a-3p mimic, miR-548a-3p inhibitor, TPX2 overexpression, and TPX2 siRNA constructs to study the effects of miR-548a-3p and TPX2. Cellular functional experiments included cell counting kit-8 assay, BrdU incorporation assay, and wound healing assay. In addition, luciferase reporter assay was applied to detect the regulatory association between miR-548a-3p and TPX2. Results: TPX2 and miR-548a-3p were identified as the interested mRNA and miRNA by microarray analysis. In CC tissues and cell lines, miR-548a-3p with low expression and TPX2 with high expression were observed. What's more, exogenous overexpressed miR-548a-3p impaired the cell viability, cell proliferation, and cell migration, while TPX2 overexpression enhanced the malignancy phenotypes. However, the promotion effect of TPX2 on CC cells was impaired by miR-548a-3p. Conclusion: This study revealed that miR-548a-3p attenuated the development of CC by targeting TPX2.

hsa-miR-7-5p suppresses proliferation, migration and promotes apoptosis in hepatocellular carcinoma cell lines by inhibiting SPC24 expression.

Emerging evidence suggests that microRNAs (miRNAs) participate in hepatocellular carcinoma (HCC) progression. Nevertheless, the mechanism of miR-7-5p in HCC cells has not been researched. In the research, the underlying biological function of miR-7-5p and SPC24 in HCC was explored. qRT-PCR was performed to measure the miR-7-5p and SPC24 level in HCC tissues and cells. The effect of miR-7-5p on HCC progression was detected by performing CCK-8, BrdU, and transwell assay. The relationship between miR-7-5p and SPC24 was determined using luciferase and RNA pull-down assays. Our findings showed that miR-7-5p was downregulated in HCC whereas SPC24 was upregulated in HCC. It was also showed that miR-7-5p upregulation restricted malignant behaviors of HCC cells, but this inhibitory effect of miR-7-5p could be relieved by its target gene SPC24. In conclusion, this research suggested that by inhibiting SPC24, miR-7-5p could act as a tumor inhibitory factor in HCC.

A panel of 8 miRNAs as a novel diagnostic biomarker in pancreatic cancer.

Pancreatic cancer (PC) is one of the major causes of cancer mortality in developed countries. Therefore, there is an urgent need to derive biomarkers for early diagnosis of PC patients at high risk.This study was designed to identify a panel of miRNAs that might serve as biomarkers for the early diagnosis of PC.The data containing both PC and control samples were extracted from the Gene Expression Omnibus (GEO) database. EdgeR was applied to identify the differentially expressed miRNAs and genes between PC patients and healthy controls. Then a miRNA-mRNA network was constructed based on the differentially expressed miRNAs and genes. The miRNAs-based biomarker for PC was finally constructed by random forest. Finally, AUC was used to evaluate the performance of miRNAs to classify PC and control samples.A total of 33 differentially expressed miRNAs, 753 differentially expressed genes, and 8 miRNAs (hsa-mir-139, hsa-mir-31, hsa-mir-196b, hsa-mir-221, hsa-mir-203b, hsa-mir-215, hsa-mir-144, and hsa-mir-4433b) that play important roles in PC were identified. The target genes of these miRNAs were found to be mainly enriched in negative regulation of acute inflammatory response cell-substrate responses, and o-glycan processing pathways. The constructed biomarkers based on these 8 miRNAs could distinguish samples coming from PC and healthy controls.We identified a panel of eight-miRNAs that would serve as early diagnostic biomarkers for PC patients.

Development and validation of 9-long Non-coding RNA signature to predicting survival in hepatocellular carcinoma.

Primary hepatic carcinoma is 1 of the most common malignant tumors globally, of which hepatocellular carcinoma (HCC) accounts for 85% to 90%. Due to the high degree of deterioration and low early detection rate of HCC, most patients are diagnosed when they are already in the middle and advanced stages, and the prognosis are always poor.RNA sequencing data from the cancer genome atlas was used to explore differences in lncRNA expression profiles. LncRNA was extracted by gdcRNAtools in R package. Multivariate cox analysis was performed on the screened lncRNAs. The relationship between the lncRNA model and prognosis as well as clinical characteristics of patients with HCC was analyzed. Finally, a predictive nomogram in the the cancer genome atlas cohort was established and verified internallyBased on the RNA sequencing survival analysis, a 9- lncRNAs prognosis model, including TMCC1-AS1, AC008892.1, AL031985.3, L34079.2, U95743.1, KDM4A-AS1, SACS-AS1, AC005534.1, LINC01116 was established. The 9-lncRNA prognosis model was a reliable tool for predicting prognosis of HCC, and the nomogram of this prognosis model could help clinicians to choose personalized treatment for HCC patientsThis model was significant to complement clinic characteristics of HCC and to promote personalized management of patients, it also provided a new idea for researches on the prognosis of HCC.

Survivals of patients with pancreatic neuroendocrine carcinomas: An in-depth analysis by the American Joint Committee on Cancer 8th tumor-node-metastasis staging manual.

Recently, the American Joint Committee on Cancer (AJCC) 8th staging manual stipulated the World Health Organization (WHO) G3 pancreatic neuroendocrine carcinomas (p-NECs) should all be classified by the system for pancreatic exocrine adenocarcinomas, which had ignored the heterogeneity of G3 p-NECs. We focused on demonstrating whether the heterogeneous subgroups of G3 p-NECs would influence the accurate application of AJCC 8th staging systems.G3 p-NECs were divided into well-differentiated and poorly-differentiated subgroups, whose clinical features and overall survival (OS) were compared. Survival analysis by applying 2 new AJCC 8th staging systems to well-differentiated G3 p-NECs were performed to validate whether these subgroup patients should also be staged by the system proposed for all G3 p-NECs.We enrolled 172 patients who were histopathologically diagnosed as G3 p-NECs, including 64 well-differentiated G3 p-NECs and 108 poorly-differentiated ones, whose patient demographics and tumor characteristics present no notably differences (P > .05), except their Ki-67 index and mitotic rate (P = .031, P = .025; respectively). The estimated OS of well-differentiated G3 p-NECs was significantly better than those of poorly-differentiated tumors (P < .001). When applying the new AJCC system for all G3 p-NECs to well-differentiated G3 tumors, 18, 22, 12, and 12 patients were respectively distributed in the new AJCC Stage I, Stage II, Stage III, and Stage IV. Using the AJCC 8th staging system for WHO G1/G2 pancreatic neuroendocrine tumors (p-NETs) to well-differentiated G3 p-NECs, there were 5, 25, 22, and 12 patients classified from the new AJCC Stage I to Stage IV, respectively. The system for G1/G2 p-NETs could significantly differentiate the survival differences between each new stage of well-differentiated G3 p-NECs (P < .05), while comparisons of survivals between Stage II with Stage III or Stage III with Stage IV by the system for G3 p-NECs were not statistically different (P = .334, P = .073; respectively).G3 p-NECs were heterogeneous with well-differentiated and poorly-differentiated subgroups. Both AJCC 8th staging systems proposed for all G3 p-NECs and G1/G2 p-NETs were practical for well-differentiated G3 p-NECs, while the one originally applied to G1/G2 p-NETs appeared to be superior in performance due to its better prognostic stratification and more accurate predicting ability.

Clinical outcome and long-term survival of 150 consecutive patients with pancreatic neuroendocrine tumors: A comprehensive analysis by the World Health Organization 2010 grading classification.

BACKGROUND AND OBJECTIVE: The World Health Organization (WHO) has revised its grading system for pancreatic neuroendocrine tumors (PNETs) in 2010 into three main group, which has not been widely and comprehensively evaluated. We aimed to validate the clinical valve of this system associated with the clinical outcome and long-term survival when applied to PNETs, which were rare and heterogeneous. METHODS: We retrospectively collected and analyzed the data of 150 consecutive patients with PNETs who underwent a resection. RESULTS: Sixty-four males and 86 females with PNETs were enrolled in our study. The clinical stage from I to IV by European Neuroendocrine Tumor Society were respectively defined in 53, 60, 19 and 18 patients. Seventy-two patients were pathologically diagnosed as neuroendocrine tumor G1 (NET G1), 48 as neuroendocrine tumor G2 (NET G2) and 30 as neuroendocrine carcinoma G3 (NEC G3). Patients with a radical resection obtained a notably higher overall survival (OS) than that of patients who underwent a palliative surgery (P=0.001). The 5-year OS of patients with NET G1 was significantly higher than that of patients with NET G2 (P=0.015) and NEC G3 (P<0.001); the comparison of OS for patients with NET G2 and NEC G3 was also statistically significant (P=0.005). In both univariate and multivariate analysis, clinical staging by ENETS (stage I and II vs. stage III and IV), resection (radical vs. palliative) and WHO 2010 grading classification (NET G1 and G2 vs. NEC G3) were validated to be independent predictors for the survivals of PNETs. CONCLUSION: The newly-updated WHO 2010 grading classification was prognostic for the OS of PNETs and could be widely adopted in clinical practice.

An observational and comparative study on intraductal papillary mucinous neoplasm of the biliary tract and the pancreas from a Chinese cohort.

BACKGROUND: Intraductal papillary mucinous neoplasms of the biliary tract (BT-IPMNs) are unique but very rare biliary tumors. The relationship between BT-IPMNs and intraductal papillary mucinous neoplasm of the pancreas (P-IPMNs) was still unclear and controversial. OBJECTIVE: We aimed to evaluate the clinical, radiological, histopathological, and prognostic characteristics of BT-IPMNs and P-IPMNs to achieve a better understanding of these two rare bilio-pancreatic diseases and their connections. METHODS: Data of a total of 116 patients who were all surgically treated and histopathologically diagnosed as BT-IPMNs or P-IPMNs from January 2004 to December 2014 in our single institution was all retrospectively collected and analyzed. RESULTS: This study respectively enrolled 32 patients with BT-IPMNs and 84 ones with P-IPMNs. The differences between BT-IPMNs and P-IPMNs in age, sex ratios, clinical presentation, elevated tumor markers and proportion of malignancy were not statistically significant (P>0.05), while the tumor diameter of BT-IPMNs was notably smaller than P-IPMNs (1.72cm, 4.56cm, respectively; P=0.028). Patients with BT-IPMNs were more likely manifest the symptoms of cholangitis, compared to those with P-IPMNs who showed pancreatitis (75%, 30%, respectively; P=0.039). Bile duct dilatation (100%), tumor of bile duct cavity (50%) or/and cystic dilatation of the bile duct (50%) were the typical manifestations of preoperative imaging examinations of BT-IPMNs, in which tumors were mainly located in intrahepatic or hepatic hilar region (26, 81%). Surgery has been the curable treatment for BT-IPMNs in which left hepatic lobectomy was the most commonly performed procedure (20, 63%). Finally, compared with P-IPMNs, the overall mean survival time of patients with BT-IPMNs was a little shorter (59.1mon, 86.7mon, respectively; P=0.002). CONCLUSION: BT-IPMNs are a sort of rare and separate biliary tract neoplasm, which might be related with the stones of biliary tract or the infections of parasite. Although arising in different organs and representing different features, BT-IPMNs and P-IPMNs shared considerable clinical and pathological similarities which might represent related or similar development process in the bilio-pancreatic duct systems.

CASP 3 genetic polymorphisms and risk of Hepatocellular carcinoma: a case-control study in a Chinese population.

Caspase (CASP) 3 is an important caspase in the apoptosis pathway and plays an important role in the development and progression of cancer. We hypothesized that genetic variants in CASP 3 may modify individual susceptibility to hepatocellular carcinoma (HCC). Five hundred HCC cases in West China Hospital were selected, and 500 healthy cases with the same gender, age (±5 years), and residence place were selected as control group, with proportion of 1:1. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method was performed to detect these polymorphisms. Among the 500 cases and 500 controls with DNA samples, the genotyping was successful for the CASP3 polymorphisms (rs6948, rs1049216, and rs12108497) in 486 HCC cases and 495 controls, which were included in the final analyses.The results showed that the genotype frequencies of the CASP3 did not differ significantly between the HCC patients and the control group (P > 0.05). However, when stratifying by age, sex, smoking, drinking, HBV carrier status, and family history of cancer, we found that the variant genotypes (CT + TT) of the CASP3 rs12108497 were associated with a significant increased risk of HCC among smoking individuals (adjusted OR = 2.31, 95 % CI = 1.11-4.79). No significant association was observed between the other two polymorphisms of the CASP3 gene and risk of HCC in any stratification analysis. These results suggest that the CASP3 rs12108497 polymorphism may play a role in the development of HCC among smoking individuals in the Chinese population.

Association of a p73 exon 2 G4C14-to-A4T14 polymorphism with risk of hepatocellular carcinoma in a Chinese population.

P73, a p53 homolog, has some p53-like activities and plays an important role in modulating cell cycle, apoptosis, and DNA repair. A potentially functional dinucleotide polymorphism, G4C14-to-A4T14, has been identified in the 5' untranslated region of exon 2 of the p73 gene, which may theoretically form a stem-loop structure and affect gene expression. We hypothesized that genetic variants in p73 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis that these two common variants play a role in HCC susceptibility, we conducted a hospital-based case-control study of 476 HCC patients and 526 cancer-free controls in a Chinese population. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method was performed to detect these polymorphisms. The results showed that the genotype and allele frequencies of the p73 G4C14-A4T14 did not differ significantly between the HCC patients and the control group (all P values are above 0.05). However, with stratification analysis by age, sex, smoking status, drinking status, HBV carrier state, and family history of cancer, we found that the variant genotypes (GC/AT + AT/AT) of the p73 G4C14-A4T14 was associated with a significant increased risk of HCC among HbsAg-positive individuals (adjusted OR = 2.19, 95 % CI = 1.25-3.83) and among women (adjusted OR = 2.62, 95 % CI = 1.47, 4.66). These results suggest that the p73 G4C14-to-A4T14 dinucleotide polymorphism may play a role in the development of chronic HBV-infected HCC in the Chinese population, especially among women.