Expression Levels Of H19 Research Articles

Long noncoding RNA H19 acts as a miR-340-3p sponge to promote epithelial-mesenchymal transition by regulating YWHAZ expression in paclitaxel-resistant breast cancer cells.

Breast cancer (BC) is the leading cause of cancer-related death in women worldwide and one of the most prevalent malignancy. In recent years, increasing evidence had illuminated that long noncoding RNAs (lncRNAs) serve as critical factors in multiple tumor progression, including BC. Emerging references had indicated that the lncRNA H19 acts as significant roles in tumor progression and epithelial-mesenchymal transition (EMT). However, the underlying molecular mechanisms and biological roles of H19 in BC invasion, metastasis and EMT are still unclear. In this study, it was detected that the expression level of H19 was increased in BC paclitaxel-resistant (PR) cells subline (MCF-7/PR) in comparison with MCF-7 parental cells. In vitro, there were demonstrated that H19 overexpression promoted BC cells proliferation, metastasis, invasion and EMT procedures, and suppressed cells apoptosis. Whereas, H19 suppression resulted in the contrary biological effects. Besides, bioinformatics tools and dual-luciferase reporters assays indicated that miR-340-3p could act as a potential target gene of H19, the underlying mechanism studies proved that H19 could act as a competing endogenous RNA (ceRNA) via competitively binding miR-340-3p to promote BC cell proliferation, metastasis and EMT by regulating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) and potentiate the Wnt/β-catenin signaling in BC cells. In summary, our findings demonstrated that H19 could act as a ceRNA in BC progression, metastasis and EMT through modulating miR-340-3p/YWHAZ axis and activating the canonical Wnt/β-catenin signaling pathway, indicating that H19 might act as an underlying therapeutic target and prognostic biomarker for BC therapy.

The relationship between H19 and parameters of ovarian reserve

ContextThe H19 long noncoding RNA (lncRNA) belongs to a highly conserved, imprinted gene cluster involved in embryonic development and growth control. We previously described a novel mechanism whereby the Anti-mullerian hormone (Amh) appears to be regulated by H19. However, the relationship between circulating H19 and markers of ovarian reserve including AMH not been investigated.ObjectiveTo determine whether H19 expression is altered in women with decreased ovarian reserve.DesignExperimental study.SettingYale School of Medicine (New Haven, USA) and Gazi University School of Medicine (Ankara, Turkey).Patients or other participantsA total of 141 women undergoing infertility evaluation and treatment.InterventionCollection of discarded blood samples and cumulus cells at the time of baseline infertility evaluation and transvaginal oocyte retrieval, respectively.Main outcome measureSerum and cumulus cell H19 expression.ResultsWomen with diminished ovarian reserve (as determined by AMH) had significantly lower serum H19 expression levels as compared to controls (p < 0.01). Serum H19 was moderately positively correlated with serum AMH. H19 expression was increased 3.7-fold in cumulus cells of IVF patients who demonstrated a high response to gonadotropins, compared to low responders (p < 0.05).ConclusionIn this study, we show that downregulation of H19 in serum and cumulus cells is closely associated with decreased ovarian reserve, as measured by decreased AMH levels and reduced oocyte yield at oocyte retrieval. Further study with expanded sample sizes is necessary to determine whether H19 may be of use as a novel biomarker for diminished ovarian reserve.

Expression level of long noncoding RNA H19 of normotensive placentas in late pregnancy relates to the fetal growth restriction.

Infants with fetal growth restriction (FGR) are at an increased risk of perinatal morbidity and mortality. The long noncoding RNA H19 gene is expressed abundantly in placental villi and recent studies suggest that it regulates FGR. However, the role of H19 in the FGR placenta remains unclear. This study aimed to clarify the relationship between H19 expression and FGR using normotensive placentas after 34 weeks of gestation. Formalin-fixed paraffin-embedded tissues from human placentas collected from pregnancies resulting in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns were used. The histopathological features of placenta tissues, such as villous stromal fibrosis, the numbers of terminal villi, villous vessels and cytotrophoblasts were analyzed using hematoxylin and eosin, Masson's trichrome staining and immunostaining. The localization and expression of H19 in the placentas were demonstrated by in situ hybridization and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. Moreover, the expression levels of H19-regulated molecules such as IGF2 and decorin (DCN) were measured by RT-qPCR. Histopathological features of the placental villous were not different between placentas associated with SGA and AGA. H19 localized to the villous stroma, endothelial cells and cytotrophoblasts. Moreover, the expression level of H19 in SGA placentas was significantly lower than that in AGA placentas. The expression levels of IGF2 and DCN in SGA placentas tended to be lower than those in AGA placentas similarly to H19. This study highlights the potential importance of regulatory events mediated by H19 in SGA placentas without histopathological abnormalities in late pregnancy.

Altered levels of MALAT1 and H19 derived from serum or serum exosomes associated with type-2 diabetes.

Environmental, genetic and epigenetic risk factors have been closely related to the development of type-2 diabetes (T2D). It has been reported that the expression in H19 and MALAT1 are related to metabolic diseases. To analyze the relationship between the expression of H19 and MALAT1 lncRNAs with diabetic patients. A study was conducted in subjects with T2D and nondiabetic controls, residents of Mexico City. Anthropometric measurements were made, and serum concentrations of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol were analyzed. Total RNA was extracted from serum and serum exosomes. The H19 and MALAT1 expression levels were quantified by RT-qPCR. A significant reduction in the expression of MALAT1 from serum or serum exosomes were found in patients with T2D, metabolic syndrome and low levels of HDL-c. Significant increase in H19 levels was found in diabetic subjects with poor glycemic control. Additionally, the principal component analyzes showed that serum MALAT1 expression was associated with total cholesterol and HDL-c levels, and the exosomes H19 expression was associated with waist circumference. The results obtained suggest that MALAT1 expression levels could be an epigenetic biomarker of diabetes risk or of its comorbidities.

Determination of Serum Exosomal H19 as a Noninvasive Biomarker for Breast Cancer Diagnosis.

PurposeThere is an urgent need for new biomarkers for the diagnosis of breast cancer. Exosomes can communicate with cells through transport molecules, including long-chain noncoding RNA (lncRNA), which is considered as a promising noninvasive biomarker. Here, we aimed to determine the potential of long noncoding RNA (lncRNA) H19 in the circulating exosomes for the diagnosis of breast cancer (BC).Materials and MethodsWe measured the levels of lncRNA H19 in serum-derived exosomes from patients with breast cancer (BC) or benign breast disease (BBD) and healthy subjects, using quantitative real-time PCR. H19 levels were also measured for pre-operative and post-operative patients. Receiver operating characteristic curve was constructed, and the area under the curve (AUC) was calculated to determine the applicability of exosomal H19 levels as biomarkers in BC. The relationship between H19 relative expression and clinical features of BC patients was also analyzed.ResultsExosomal H19 expression levels were upregulated in patients with BC compared to that in patients with BBD and healthy controls (BC vs BBD, P < 0.001; BC vs healthy subjects, P < 0.001). The median serum exosomal H19 levels were significantly lower in post-operative than that in the pre-operative patients (P < 0.001). The AUC for exosomal H19 analysis was 0.870 (95% CI: 0.774–0.966) with a sensitivity of 87.0% and specificity of 70.6%, which was higher than the AUCs for CA15-3 and CEA, ie, 0.822 and 0.811, respectively. Moreover, exosomal H19 expression levels were associated with lymph node metastasis (P = 0.039), distant metastasis (P = 0.008), TNM stages (P = 0.022), ER (P=0.009), PR (P = 0.018), and Her-2 (P = 0.021).ConclusionOur results indicated that serum exosomal H19 acts as a novel biomarker for the diagnosis of BC.

Expression and prognostic value of long non-coding RNA H19 in glioma via integrated bioinformatics analyses.

Numerous discoveries have elucidated that long noncoding RNAs (lncRNAs) play a critical role in cancer malignant progression. However, their potential involvement in gliomas remains to be explored. Herein, the expression level of lncRNA H19 in glioma tissues, and its relevance with clinical characteristics were analyzed through Oncomine. The results showed that H19 was highly expressed in glioma tissues and its expression increased with the increase of malignancy. Next, GTEx and TCGA data were downloaded for differently expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the correlation analyses between H19 expression and clinic features. Radiation therapy had a good effect on glioblastoma multiforme (GBM), but didn’t have a good effect on low grade glioma (LGG). Meanwhile, the expression level of H19 could act as an indicator molecule indicating the effect of radiotherapy. Finally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted. It was found that H19 could affect the immune infiltration level of glioma through copy number variations, thus affecting the prognosis of glioma patients. Collectively, H19 may be involved in the occurrence and development of glioma, and has potential reference value for the relief and immunotherapy of glioma.

Overexpression of lncRNA H19 leads to reduced proliferation in TSCC cells through miR-675-5p/GPR55.

BackgroundTongue squamous cell carcinoma (TSCC) is a highly malignant tumor and oral disease. We intended to identify the function and mechanism of lncRNA H19 in TSCC.MethodsTwenty-two TSCC samples were obtained, and expression levels of lncRNA H19 were measured by quantitative real time PCR (qRT-PCR). After experimentally upregulating expression of lncRNA H19 in TSCC cells, proliferation, invasion and migration were assessed. Further, dual-luciferase reporter gene assays were used to examine the relationship between lncRNA H19 and GPR55.ResultsLncRNA H19 was expressed at lower levels in TSCC tissues than in normal tissues. When lncRNA H19 was overexpressed, miR-675-5p expression levels were also upregulated, leading to reduced proliferation, invasion and migration of CAL27 and SCC9 cells. Dual-luciferase reporter gene assays revealed that miR-675-5p binds to GPR55, which might promote growth in TSCCs.ConclusionsThe lncRNA H19/miR-675-5p/GPR55 axis might inhibit cell proliferation, invasion and migration in TSCC.

Circulating long noncoding RNAs H19 and GAS5 are associated with type 2 diabetes but not with diabetic retinopathy: A preliminary study.

Recently, a wide range of biological and pathological roles of long noncoding RNAs (lncRNAs) have been discovered. However, the potential role of circulating lncRNAs H19 and GAS5 in type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) is not clear. Here, we assessed the plasma levels of H19 and GAS5 lncRNAs in T2DM patients with/without DR and evaluated if H19 and GAS5 pre-treatment plasma levels are a predictor of early response to a single aflibercept dose in DR subgroup. Plasma lncRNA expression profiles of 119 T2DM patients (66 with DR and 53 without DR) and 110 healthy controls were determined by quantitative reverse transcription PCR. The association of lncRNA expression profiles with clinical features and aflibercept early response in DR patients was investigated. Relative H19 expression levels were significantly increased in T2DM group (including DR and non-DR subgroups) vs. controls, while GAS5 levels were decreased in T2DM group (p < 0.001). There was no significant difference in H19 and GAS5 expression levels between DR and non-DR subgroups. H19 and GAS5 expression profiles were not significantly correlated with clinical parameters or response to aflibercept therapy in DR subgroup. Our findings indicate that the circulating lncRNAs H19 and GAS5 may be associated with T2DM prevalence but may not have an important diagnostic/prognostic role in DR or early response to aflibercept intravitreal injection in DR patients. Large-scale transcriptomic studies are warranted to validate our results and investigate other lncRNA candidates in T2DM.

LncRNA H19 is involved in myocardial ischemic preconditioning via increasing the stability of nucleolin protein.

Myocardial ischemic preconditioning (IP) is defined as a brief period of myocardial ischemia/reperfusion (I/R) that significantly reduces injury during the subsequent exposure to long-term I/R. However, the underlying mechanisms of myocardial IP are yet to be elucidated. This study investigated the expression and roles of long noncoding RNA (lncRNA) H19 in myocardial IP in vitro and in vivo. LncRNA H19 expression levels were analyzed by quantitative reverse-transcription polymerase chain reaction, cell viability was determined by the Cell Counting Kit-8 assay, apoptosis was evaluated based on the caspase 3 activity, and RNA immunoprecipitation was performed to examine the interaction between lncRNA H19 and nucleolin. The results of this study showed that lncRNA H19 expression was significantly upregulated in mouse hearts subjected to myocardial IP, in rat H9C2 cells exposed to H2 O2 preconditioning (H2 O2 -PC), and in neonatal rat cardiomyocytes subjected to hypoxia preconditioning. H19 knockdown abrogated the H2 O2 -PC-mediated protection in cardiomyocytes evidenced by the decreased cell viability and increased caspase-3 activity. Conversely, H19 overexpression enhanced the protective role of H2 O2 -PC in cardiomyocytes. In addition, H19 overexpression increased the expression of nucleolin, whereas H19 ablation abrogated H2 O2 -PC-induced upregulation of nucleolin in cardiomyocytes. Furthermore, H19 overexpression increased the stabilization of nucleolin; an interaction between H19 and nucleolin was identified using the RNA-protein interaction studies. Furthermore, nucleolin small interfering RNA relieved the protective role of lncRNA H19. These findings demonstrated that the lncRNA H19 is involved in myocardial IP via increasing the stability of nucleolin protein and lncRNA H19 may represent a potential therapeutic target for the treatment of the myocardial injury.

Increased Expression Level of Long Noncoding RNA H19 in Plasma of Patients with Myocardial Infarction.

Long noncoding RNAs (lncRNAs) are lengthy noncoding transcripts which are actively involved in crucial cellular pathways. Tissue-specific expression of lncRNAs besides its secretion into the body fluids, has made lncRNAs in attention as biomarkers of the diseases. According to the role of lncRNAs, especially H19 in cardiac regeneration, it is not surprising if their altered expression levels lead to cardiac diseases. In the present study, the relative expression of H19 was compared in the plasma of atherosclerotic myocardial infarction and control individuals by real time-PCR, and data were normalized using GAPDH. The association of plasma level of lipid and homocystine with H19 expression was also considered. The potential of H19 to discriminate the case from control was studied using the ROC analysis. We found that the plasma level of H19 transcript significantly increased in the plasma of patients in comparison with the control group. Additionally, the relative expression level of H19 was directly associated with the plasma homocystine level. The relative expression of H19 at threshold of 0.3 showed 70% sensitivity and 94% specificity to discriminate cases from controls. This study revealed that the expression level of H19 may be considered as a biomarker of myocardial infarction, although further studies are needed to generalize this finding.

The possibility of benomyl and diazinon pesticide’s carcinogenicity and the potential of hotair and H19 as a serum biomarker in breast cancer

Evidence had grown ever stronger that pesticides can cause epigenetic modifications such as changing the expression of noncoding RNAs which have positive associations with incidence of cancer. Upregulation of two oncogenic long non coding RNAs, HOX antisense intergenic RNA and H19, enhances breast cancer. This study was conducted to investigate and compare the effect of 7,12-dimethylbenz(a)anthracene (proven to cause breast cancer) with two commonly used pesticides named benomyl and diazinon (suspected of developing breast cancer) on the expression level of HOX antisense intergenic RNA and H19. Mice were intragastrically exposed to 7,12-dimethylbenzathracene, diazinon and benomyl for 60 days. The expression level of H19 and HOX antisense intergenic RNA were measured by Real-Time PCR. The findings revealed that the expression of long non coding RNAs in pesticides and 7,12-dimethylbenzathracene treated mice were significantly higher than untreated control. This study, for the first time, has demonstrated that diazinon and benomyl pesticides could cause upregulation of both oncogenic H19 and HOX antisense intergenic RNA. Since 7,12-dimethylbenz(a)anthracene induced breast tumors, similar results of all three experimental groups could be a testimony to the carcinogenicity of these pesticides and provides support for the importance of these noncoding RNAs as a target for therapeutic intervention in breast cancer.

The prognostic value of long non-coding RNA H19 in various cancers: A meta-analysis based on 15 studies with 1584 patients and the Cancer Genome Atlas data.

Recent studies have shown that long noncoding RNA (lncRNA) H19 is aberrantly expressed in various cancers. However, the prognostic significance of H19 in cancer patients remains to be elucidated. Here, we designed and conducted a meta-analysis to evaluate the prognostic value of this lncRNA for malignant solid neoplasms. Relevant publications were collected from PubMed, Cochrane Library, Web of Science, and Embase databases. The relevant survival data of patients with H19-associated cancers were downloaded from The Cancer Genome Atlas (TCGA) project. Statistically significant relationships between H19 expression levels and overall survival were analyzed by hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). A total of 15 studies with 1584 patients were ultimately included for this literature meta-analysis. An elevated level of H19 expression was found to be negatively correlated with the overall survival (OS) (HR = 1.62, 95% CI = 1.36-1.93, P < .001) in various cancers. Abnormal H19 expression was also positively correlated with poor tumor differentiation (P < .0001), more advanced clinical stage (P < .0001), earlier lymph node metastasis (P < .0001), and earlier distant metastasis (P < .05). The relationship between elevated H19 expression and overall survival was further validated by a TCGA dataset consisting of 7462 cancer patients (HR = 1.12, 95% CI = 1.03-1.22, P < .05). Our study indicates that H19 expression is closely relevant to clinical outcome and suggests that lncRNA H19 could be a crucial prognostic biomarker for certain carcinoma types.

The Role of LncRNA H19 in MAPK Signaling Pathway Implicated in the Progression of Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD), also known as neonatal chronic lung disease, is an important cause of respiratory illness in preterm newborns that results in significant morbidity and mortality. Long noncoding RNAs (lncRNAs) have been discovered with many biological functions. However, the role of lncRNAs in the pathogenesis of BPD remains poorly understood. Here, we established a mouse lung injury model that mimicked human BPD. Subsequently, we found the lncRNA H19 expression level was significantly increased in BPD compared with normal lung tissues using quantitative real-time polymerase chain reaction. Next, we observed that overexpression of lncRNA H19 enhanced mitogen-activated protein kinase (MAPK) signaling pathway. In addition, we also found that dysfunction of lncRNA H19 altered the expression of inflammatory factors. Thus, our study validates that lncRNA H19 contributes to the progression of BPD by regulating MAPK signaling pathway, which could be used as a potential target for treating BPD.

Decreased H19, GAS5, and linc0597 Expression and Association Analysis of Related Gene Polymorphisms in Rheumatoid Arthritis

Long noncoding RNAs (lncRNAs) widely participate in human diseases by regulating gene transcription, modulating protein function, or acting as ceRNAs. Yet, their roles in rheumatoid arthritis (RA) remain obscure. In this study, the expression of three lncRNAs (H19, GAS5, and linc0597) in peripheral blood mononuclear cells (PBMCs) were detected in 77 RA patients and 78 controls using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The association of lncRNAs related gene polymorphisms with RA were evaluated in 828 RA patients and 780 controls using TaqMan single nucleotide polymorphism (SNP) genotyping assays. We observed that the expression levels of H19, GAS5 and linc0597 were down-regulated in PBMCs of RA patients, of which GAS5 level decreased in patients with hypocomplementemia, and negatively correlated with C-reactive protein (CRP) level in RA patients. Moreover, we highlighted two related potential functional SNPs, GAS5 rs6790 and linc0597 rs2680700 for associations with RA susceptibility. The precise roles of these lncRNAs in mechanism of RA remain to be further explored.

FOXF2 aggravates the progression of non-small cell lung cancer through targeting lncRNA H19 to downregulate PTEN.

To illustrate the role of FOXF2 in the aggravation of the progression of non-small cell lung cancer (NSCLC) by targeting long non-coding RNA (lncRNA) H19 to down-regulate the gene of phosphate and tensin homolog deleted on chromosome ten (PTEN). The relative levels of FOXF2 and H19 in NSCLC tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the expression levels of FOXF2 and H19 was analyzed. Kaplan-Meier curves were depicted for uncovering the prognostic value of FOXF2 in NSCLC patients. The proliferative and migratory abilities of A549 cells influenced by FOXF2 were also assessed. The interaction between FOXF2 and H19 was evaluated through chromatin immunoprecipitation (ChIP) assay and Western blot, so did the association between H19 and PTEN. Finally, rescue experiments were conducted to explore the role of FOXF2/H19/PTEN axis in regulating the viability and migration of A549 cells. FOXF2 and H19 were upregulated in NSCLC and a positive correlation was observed between the two genes. High level of FOXF2 indicated a worse prognosis in NSCLC patients. The knockdown of FOXF2 attenuated the proliferative and migratory abilities of A549 cells. FOXF2 could bind to the promoter region of H19 and accelerated its transcription. Moreover, H19 could recruit EZH2 to bind to PTEN. The overexpression of H19 could reverse the regulatory effects of FOXF2 on the viability and migration of A549 cells. FOXF2 was upregulated in NSCLC. It accelerated the proliferative and migratory abilities of the NSCLC cells by targeting H19 to downregulate PTEN, thus aggravating the progression of NSCLC.

Are Long Noncoding RNAs New Potential Biomarkers in Gastrointestinal Stromal Tumors (GISTs)? The Role of H19 and MALAT1.

Long noncoding RNAs (lncRNAs) are emerging as key regulators of genetic and epigenetic networks, and their deregulation may underlie complex diseases, such as carcinogenesis. Several studies described lncRNA alterations in patients with solid tumors. In particular, HOTAIR upregulation has been associated with tumor aggressiveness, metastasis, and poor survival in gastrointestinal stromal tumor (GIST) patients. We analyzed expression levels of other lncRNAs, H19 and MALAT1, in FFPE tissue specimens from 40 surgically resected and metastatic GIST patients, using real-time PCR analysis. H19 and MALAT1 were both upregulated in 50% of GIST patients. MALAT1 lncRNA expression levels seem to be correlated with c-KIT mutation status. The percentage of both H19 and MALAT1 upregulation was significantly higher in patients with time to progression (TTP) < 6 months as compared to patients with TTP > 6 months. The median TTP was significantly lower in patients with both H19 and MALAT1 lncRNA upregulation as compared to those with lncRNA downregulation. These data suggest a potential role for both H19 and MALAT1 lncRNAs as prognostic biomarker for the clinical selection of the best candidate to first-line treatment with imatinib.

The role of long non-coding RNA H19 in breast cancer.

Breast cancer is the most common malignant tumor in women in the majority of countries, such as China, Britain and Australia, and its morbidity and mortality rates remain very high. Long non-coding RNAs (lncRNAs) are non-coding RNAs (ncRNAs) >200 nucleotides in length that lack open reading frames. LncRNA H19 is a transcription product of the H19 gene, and the aberrant expression of H19 can be demonstrated in various types of tumor cell. The purpose of the present review was to elaborate the role of H19 in breast cancer. H19 can regulate gene expression in breast cancer at multiple levels, including epigenetic, transcriptional and posttranscriptional. The abnormal expression of H19 is closely associated with the tumorigenesis and progression of breast cancer via different underlying molecular mechanisms, such as encoding microRNA-675, competing endogenous RNA regulation and interacting with MYC. A large number of clinical studies have suggested that H19 can serve as a potential biomarker for the diagnosis of breast cancer. High expression levels of H19 increases the drug resistance of breast cancer cells and is associated with poor prognosis within patients with breast cancer. Therefore, serum H19 levels may have momentous significance in the clinical setting.

Long non-coding RNA H19 modulates proliferation and apoptosis in osteoarthritis via regulating miR-106a-5p

Osteoarthritis (OA), a type of joint diseases, could result in breakdown of joint cartilage and underlying bone. Accumulating evidences suggested that long non-coding RNAs play important roles in OA progression. However, the underlying mechanism of H19 in OA is still not fully explored. The expression levels of H19 and miR-106a-5p in OA samples from patients or cultured chondrocytes were examined by quantitative real time polymerase chain reaction. Cell proliferation and apoptosis were analysed by MTT assay and flow cytometry, respectively. Western blotting was employed to detect the expression levels of PCNA, CyclinD1, Caspase 3 and Cleaved Caspase 3. StarBase database, luciferase assay and RNA immunoprecipitation were introduced to confirm the relationship between H19 and miR-106a-5p. The correlation of H19 and miR-106a-5p was analysed by Spearman rank analysis. H19 expression was upregulated, while miR-106a-5p level was downregulated in OA samples and IL-1b-treated chondrocytes. H19 overexpression inhibited the proliferation and induced apoptosis in IL-1b-treated chondrocytes, while H19 knockdown induced the opposite effect. Luciferase and RIP assay demonstrated that miR-106a-5p was a direct target of H19. miR-106a-5p overexpression led to proliferation promotion and apoptosis inhibition in chondrocytes treated by IL-1β and it reversed the effect of H19 addition. We conclude that H19 could regulate proliferation and apoptosis of chondrocytes treated by IL-1β in OA via sponging miR-106a-5p.

Invitro and invivo studies on the association of long non‑coding RNAs H19 and urothelial cancer associated 1 with the susceptibility to 5‑fluorouracil in rectal cancer.

There is no predictive biomarker for response to 5‑fluorouracil (5FU)‑based neoadjuvant chemotherapy (NAC) in rectal cancer. In the present study, we examined potential long non‑coding RNAs (lncRNAs) linked to the susceptibility to 5FU in cultured colorectal cancer cells, and in biopsy and resected tissues of 31 human rectal cancer cases treated with NAC. Candidate lncRNAs for the prediction of susceptibility to 5FU were investigated by comprehensive analysis of expression profiles of 84 lncRNAs in cultured cells using PCR array. Bioinformatic analysis identified H19 and urothelial cancer associated 1 (UCA1) as candidate biomarkers for 5FU susceptibility. Quantitative PCR of H19 and UCA1 in cultures of colorectal cancer cells demonstrated the notable variation in expression. The ratios of changes of H19 and UCA1 expression in response to 5FU were low in cells resistant to 5FU, whereas ratios were high in cells susceptible to 5FU. In 5FU‑susceptible cells, cell proliferation was inhibited by 5FU. Upregulation of H19 and UCA1 were associated with the reduction in target molecule expression, including retinoblastoma and p27kip1. In 31cases of rectal cancer, H19 and UCA1 expression levels in biopsy and resected tissue were comparable. The ratios of H19 and UCA1 expression in resected tissue compared with biopsy samples were low in 17cases, whereas the ratios were high in 14cases; 11 of the 17cases (65%) with low ratios exhibited poor response to NAC, whereas 4 of the 14cases (29%) with high ratios showed poor response (P=0.045). The increase in H19 and UCA1 expression may represent the response to impaired cell cycle in cells susceptible to 5FU. Our results indicate that changes in H19 and UCA1 expression may be considered for predicting the susceptibility to 5FU‑based NAC in rectal cancer.

High level of lncRNA H19 expression is associated with shorter survival in esophageal squamous cell cancer patients

AimLong non-coding RNA (lncRNA) is currently considered to play an important regulatory role in various diseases, including tumors, at present a hot topic in research. As a non-coding transcription product of imprinted gene, LncRNA H19 is expressed as a parent imprinted maternal allele without protein-coding ability. Increasing evidence indicates that LncH19 may be a new tumor marker for early clinical diagnosis and prognosis judgment. In this study, LncH19 expression was investigated by RNA in situ hybridization for further exploring the clinicopathological role of its expression in esophageal squamous cell cancer (ESCC). Methods121 tumor samples and seven cases of adjacent non-tumor tissues from esophageal cancer patients were detected by RNA in situ hybridization (ISH) and the ISH staining was graded with modified Allred scoring. ResultsWhile no LncH19 expression in the tumor adjacent to normal epithelia was disclosed with the technology, significantly higher levels of LncH19 expression were detected in the tumors obtained from the patients who died within one year after surgery, compared to the expression in those tumors from the patients who survived longer than five years after the same treatment regimen (P = 0.001). In addition, LncH19 expression was verified to correlate with a larger tumor size (P = 0.002) and a higher UICC stage (P = 0.001). ConclusionOur LncH19 ISH data verify the involvement of LncH19 in ESCC. Higher levels of LncH19 expression were not only detected in tumors with larger size and in clinical late stage, but also significantly associated with shorter survival, strongly indicating its clinical significance in the malignant progression of ESCC and useful value as a poor prognostic factor for the patients.