Downregulation of lncRNA MIR17HG reduced tumorigenicity and Treg-mediated immune escape of non-small-cell lung cancer cells through targeting the miR-17-5p/RUNX3 axis.

Long noncoding RNA MIR17HG was involved with the progression of non-small-cell lung cancer (NSCLC), but specific mechanisms of MIR17HG-mediated immune escape of NSCLC cells were still unknown. The present study investigated the function of MIR17HG on regulatory T cell (Treg)-mediated immune escape and the underlying mechanisms in NSCLC. Expression of MIR17HG and miR-17-5p in NSCLC tissue samples were detected using quantitative real-time PCR (qRT-PCR). A549 and H1299 cells were transfected with sh-MIR17HG, miR-17-5p inhibitor, or sh-MIR17HG + miR-17-5p inhibitor, followed by cocultured with Tregs. Cell proliferation was measured using 5-ethynyl-20-deoxyuridine (Edu) staining assay and cell counting kit-8 (CCK-8) assay. Flow cytometry was used for determining positive numbers of FOXP3+CD4+/CD25+/CD8+ Tregs. Through subcutaneous injection with transfected A549 cells, a xenograft nude mouse model was established. Weights and volumes of xenograft tumors were evaluated. Additionally, the expressions of immune-related factors including transforming growth factor beta (TGF-ß), vascular endothelial growth factor A (VEGF-A), interleukin-10 (IL-10), IL-4, and interferon-gamma (IFN-γ) in cultured cells, were evaluated by enzyme-linked immunosorbent assay and western blot analysis. Then, miR-17-5p was decreased and MIR17HG was enhanced in both NSCLC tissues and cell lines. MIR17HG knockdown significantly suppressed cell proliferation, tumorigenicity, and immune capacity of Tregs in A549 and H1299 cells, whereas sh-MIR17HG significantly reduced expression levels of VEGF-A, TGF-ß, IL-4, and IL-10 but promoted the IFN-γ level in vitro and in vivo. Moreover, downregulation of miR-17-5p significantly reversed the effects of sh-MIR17HG. Additionally, we identified that runt- related transcription factor 3 (RUNX3) was a target of miR-17-5p, and sh-MIR17HG and miR-17-5p mimics downregulated RUNX3 expression. In conclusion, downregulation of MIR17HG suppresses tumorigenicity and Treg-mediated immune escape in NSCLC through downregulating the miR-17-5p/RUNX3 axis, indicating that this axis contains potential biomarkers for NSCLC.

miR-17-92a-1 cluster host gene: a key regulator in colorectal cancer development and progression.

Colorectal cancer (CRC), recognized among the five most prevalent malignancies and most deadly cancers, manifests multifactorial influences stemming from environmental exposures, dietary patterns, age, and genetic predisposition. Although substantial progress has been made in comprehending the etiology of CRC, the precise genetic components driving its pathogenesis remain incompletely elucidated. Within the expansive repertoire of non-coding RNAs, particular focus has centered on the miR-17-92a-1 cluster host gene (MIR17HG) and its associated miRNAs, which actively participate in diverse cellular processes and frequently exhibit heightened expression in various solid tumors, notably CRC. Therefore, the primary objective of this research is to undertake an extensive inquiry into the regulatory mechanisms, structural features, functional attributes, and potential diagnostic and therapeutic implications associated with this cluster in CRC. Furthermore, the intricate interplay between this cluster and the development and progression of CRC will be explored. Our findings underscore the upregulation of the miR-17-92a-1 cluster host gene (MIR17HG) and its associated miRNAs in CRC compared to normal tissues, thus implying their profound involvement in the progression of CRC. Collectively, these molecules are implicated in critical oncogenic processes, encompassing metastatic activity, regulation of apoptotic pathways, cellular proliferation, and drug resistance. Consequently, these findings shed illuminating insights into the potential of MIR17HG and its associated miRNAs as promising targets for therapeutic interventions in the management of CRC.

Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages.

Circulating exosomes derived from polymicrobial sepsis contain various non-coding RNAs and proteins. Isobaric tags for a relative or absolute quantitation proteomic analysis of the exosomal content revealed 70 dysregulated proteins in the circulating exosomes from septic mice. Next-generation sequencing was used to profile the long non-coding RNA expression in primary cultured macrophages treated with exosomes obtained from the blood of septic C57BL/6 mice, and it was discovered that the nuclear factor-kappa B (NF-κB)/miR-17-92a-1 cluster host gene (MIR17HG) pathways were activated in the macrophages. The inhibition of MIR17HG expression by RNA interference resulted in significantly decreased cell viability. RNA pull-down assays of MIR17HG revealed that ten protein targets bind to MIR17HG. Interaction networks of proteins pulled down by MIR17HG were constructed using GeneMANIA, and their functions were mainly involved in ribonucleoprotein granules, type I interferons, the regulation of organelle assembly, the biosynthesis of acetyl coenzyme A, as a signal transducer and activator of transcription (STAT) protein phosphorylation, and mRNA splicing. Furthermore, RNA interference inhibited MIR17HG expression, resulting in significantly decreased cell survival. In conclusion, this work discovered considerable MIR17HG overexpression in macrophages treated with circulating exosomes from sepsis-affected animals. This study's findings assist us in comprehending the role of exosomes in modulating inflammatory responses and mediating pathogenic pathways in macrophages during sepsis.

Bioinformatics analysis proposes a possible role for long noncoding RNA MIR17HG in retinoblastoma.

BACKGROUND: Retinoblastoma (RB) is the most common prevalent intraocular malignancy among infants and children, particularly in underdeveloped countries. With advancements in genomics and transcriptomics, noncoding RNAs have been increasingly utilized to investigate the molecular pathology of diverse diseases. AIMS: This study aims to establish the competing endogenous RNAs network associated with RB, analyse the function of mRNAs and lncRNAs, and finds the relevant regulatory network. METHODS AND RESULTS: This study establishes a network of competing endogenous RNAs by Spearman correlation analysis and prediction based on RB patients and healthy children. Enrichment analyzes based on Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes are conducted to analyze the potential biological functions of lncRNA and mRNA networks. Weighted gene co-expression network analysis (WGCNA) is employed to identify gene cluster modules exhibiting the strongest correlation with RB. The results indicate a significant correlation between the lncRNA MIR17HG (R = .73, p = .02) and the RB phenotype. ceRNA networks reveal downstream miRNAs (hsa-mir-425-5p and hsa-mir455-5p) and mRNAs (MDM2, IPO11, and ITGA1) associated with MIR17Hg. As an inhibitor of the p53 signaling pathway, MDM2 can suppress the development of RB. CONCLUSION: In conclusion, lncRNAs play a role in RB, and the MIR17HG/hsa-mir-425-5p/MDM2 pathway may contribute to RB development by inhibiting the p53 signaling pathway.

Long non-coding RNA MIR17HG impedes FOSL2-mediated transcription activation of HIC1 to maintain a pro-inflammatory phenotype of microglia during intracerebral haemorrhage.

Activation and polarization of microglia play decisive roles in the progression of intracerebral haemorrhage (ICH), and lactate exposure correlates with microglia polarization. This study explores molecules influencing lactate production and microglia phenotype alteration following ICH. A murine model of ICH was induced by intracerebral injection of collagenase. The mice experienced autonomous neurological function recovery, haematoma resolution and rapid lactate production, along with a gradual increase in angiogenesis activity, neuronal recovery and an M1-to-M2 phenotype change of microglia. Galloflavin, a lactate dehydrogenase antagonist, suppressed this phenotype change and the functional recovery in mice. FOS like 2 (FOSL2) was significantly upregulated in the brain tissues from day 7 post-ICH. Overexpression of FOSL2 induced an M1-to-M2 phenotype shift in microglia and accelerated lactate production in vivo and in haemoglobin-treated microglia in vitro. Long non-coding RNA MIR17HG impeded FOSL2-mediated transcription activation of hypermethylated in cancer 1 (HIC1). MIR17HG overexpression induced pro-inflammatory activation of microglia in mice, which was blocked by further HIC1 overexpression. Overall, this study demonstrates that MIR17HG maintains a pro-inflammatory phenotype of microglia during ICH progression by negating FOSL2-mediated transcription activation of HIC1. Specific inhibition of MIR17HG or upregulation of FOSL2 or HIC1 may favour inflammation inhibition and haematoma resolution in ICH.

LncRNA MIR17HG Suppresses Breast Cancer Proliferation and Migration as ceRNA to Target FAM135A by Sponging miR-454-3p.

Breast cancer is one of the most common malignant tumors in women, and causes a large number of cancer-related deaths. The main cause of death of breast cancer patients is tumor recurrence and metastasis. Recent studies show that lncRNA (Long non-coding RNA) plays an important role in breast cancer. However, the overall biological activity and clinical consequences of the lncRNA MIR17HG in breast cancer remain unclear. Thus, we investigate how the MIR17HG/miR-454-3p network impacts breast cancer cell proliferation and migration. Given the TCGA and Oncomine databases, the researchers evaluated variations in MIR17HG expression for the survival rates of breast cancer patients. The influence of MIR17HG on cell proliferation, migration, cell cycle, and the mRNA expression level of miR-454-3p and FAM135A (family with sequence similarity 135 member A) is identified. Luciferase assay was used to detect the regulatory effect of miR-454-3p on the 3'UTR region of FAM135A, and rescue experiments demonstrated that MIR17HG can up-regulate FAM135A expression by competitively binding miR-454-3p. The effect of FAM135A on the cloning and invasion of MCF-7 cells was detected. MIR17HG expression is reduced in breast cancer tissues, and patients with greater levels of MIR17HG expression have a better prognosis. MIR17HG overexpression caused G2/M arrest in breast cancer cells according to a flow cytometry assay. FAM135A knockdown enhances breast cancer cell proliferation and clone creation, as well as two-dimensional and three-dimensional migratory capacities. Patients with high FAM135A expression in their breast cancer had a better prognosis. These novel findings indicate that MIR17HG may be a potential target for breast cancer. Our findings demonstrated that MIR17HG might suppress breast cancer cell proliferation and migration by sponge miR-454-3p through ceRNA(competing endogenous RNAs) mechanism, indicating that targeting MIR17HG may be a feasible therapeutic candidate for breast cancer.

LncRNA MIR17HG promotes the proliferation, migration, and invasion of retinoblastoma cells by up-regulating HIF-1α expression via sponging miR-155-5p.

Long non-coding RNA (lncRNA) miR-17-92a-1 cluster host gene (MIR17HG) is oncogenic in several cancers. This study was aimed to probe into its expression characteristics and biological functions in retinoblastoma (RB) and to explore its role in regulating microRNA-155-5p (miR-155-5p) and hypoxia-inducible factor-1α (HIF-1α). In this study, paired RB samples were collected, and expression levels of MIR17HG, miR-155-5p, and HIF-1α were examined by quantitative real-time polymerase chain reaction (qRT-PCR); the proliferation, migration, and invasion of RB cells were detected by cell counting kit-8 (CCK-8) and transwell assays; qRT-PCR and Western blot were used to analyze the changes of miR-155-5p expression and HIF-1α expression. We found that MIR17HG expression was significantly up-regulated in RB samples, which was negatively correlated with miR-155-5p expression. The proliferation, migration, and invasion of RB cells were promoted by MIR17HG overexpression but inhibited by MIR17HG knockdown. MiR-155-5p suppressed the proliferation, migration, and invasion of RB cells. MIR17HG positively regulated the expression of HIF-1α on both mRNA and protein levels in RB cells. Additionally, miR-155-5p was identified as a target of MIR17HG. The data in this study suggest that MIR17HG exerts oncogenic effects in RB via the miR-155-5p/HIF-1α axis.

MIR17HG: A Cancerogenic Long-Noncoding RNA in Different Cancers.

LncRNA MIR17HG, located at chromosome 13q31, plays an inevitable role in promoting tumor progressions, such as tumorigenesis, proliferation, and metastasis. Besides, lncRNA MIR17HG is rare due to its open reading frame (ORF), which can be translated to produce protein. By systematically retrieval, we summarized that MIR17HG is an emerging lncRNA that exhibits carcinogenically in osteosarcoma (OS), glioma, cervical squamous cell carcinoma (CSCC), colorectal cancer (CRC), gastric cancer (GC), atypical teratoid rhabdoid tumors (ATRT). Furthermore, a high expression level of MIR17HG protein is also linked with meningioma. Additionally, MIR17HG polymorphisms in glioma, CRC, liver cancer (LC), breast cancer (BC), head and neck squamous cell carcinoma (HNSCC), and multiple myeloma (MM) also have a large influence on cancer susceptibility, prognosis, and so on. Collectively, long non-coding RNA MIR17HG's tumor-stimulative role could be a promising therapeutic target. Besides, by investigating patients' MIR17HG single-nucleotide polymorphisms (SNPs), clinicians could also personalize the productive interventions in gene therapy or predict the diagnosis/prognosis precisely.

MicroRNA-17-92a-1 Host Gene (MIR17HG) Expression Signature and rs4284505 Variant Association with Alopecia Areata: A Case-Control Study.

Accumulating evidence indicates the implication of microRNAs (miRs) in cutaneous and hair follicle immunobiology. We evaluated, for the first time, the miR-17-92a-1 cluster host gene (MIR17HG) expression in peripheral blood of 248 unrelated alopecia areata (AA) patients compared to 244 matched controls using Real-Time qPCR. We also tested its association with different rs4284505A>G genotypes (based on TaqMan allelic discrimination PCR) and the available clinical data. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated for each genetic association model. The upregulation of miR-17 was observed in the serum of patients with alopecia compared to controls (p-value = 0.004). The ROC curve showed high diagnostic performance of miR-17 in differentiating between patients and controls (AUC = 0.85, p-value < 0.001). rs4284505*A/G heterozygotes were more susceptible to the disease (OR = 1.57, 95% CI = 1.01−2.45) under the over-dominant model. Interestingly, patients with the rs4284505*G/G genotype had a higher level of miR-17 than those with the A/A and A/G genotypes. The G/G genotype was associated with the severe phenotype (p-value = 0.038). A/G carriers were the youngest (p-value < 0.001), had more frequent scalp infection (p-value = 0.006), exhibited the worst dermatology life quality index score (p-value = 0.037), and responded less to treatment (p-value = 0.033). In conclusion, MIR17HG expression and the rs4284505 variant were significantly associated with AA and could play a role in pathogenesis and phenotype in the Egyptian population. Further multi-center studies in other ethnicities are warranted to replicate the findings.

LncRNA miR-17-92a-1 cluster host gene (MIR17HG) promotes neuronal damage and microglial activation by targeting the microRNA-153-3p/alpha-synuclein axis in Parkinson's disease.

Long noncoding RNAs (lncRNAs) have been regarded as modulators of neurodegenerative diseases. Here, we addressed the role of lncRNA miR-17-92a-1 cluster host gene (MIR17HG) in Parkinson's disease (PD). C57BL/6 mice and SH-SY5Y cells were intervened with 6-hydroxydopamine (6-OHDA) to set up PD models in vivo and in vitro. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was implemented to compare the expression of MIR17HG and miR-153-3p. Cell viability and apoptosis were estimated by 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and Western blot (WB). The expression of alpha-synuclein (α-syn, SNCA) in BV2 was validated by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity were evaluated using commercially available kits. Bioinformatics analysis, the dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and qRT-PCR were conducted to demonstrate the interactions between miR-153-3p, MIR17HG, and alpha-synuclein (SNCA). MIR17HG was up-regulated while miR-153-3p was down-regulated in PD patients, mouse models and cells. Inhibiting MIR17HG attenuated neuronal apoptosis, microglial activation and SNCA expression in PD mice. Conditioned medium from 6-OHDA-treated SH-SY5Y cells intensified microglial inflammation, while inhibition of MIR17HG or overexpression of miR-153-3p restrained the inflammatory responses. MIR17HG's function was enforced by sponging miR-153-3p and releasing the attenuation of the putative targets of miR-153-3p and SNCA. Overall, MIR17HG, by targeting miR-153-3p and up-regulating SNCA, stimulates neuronal apoptosis and microglial inflammation in PD.

KHDRBS3 promotes paclitaxel resistance and induces glycolysis through modulated MIR17HG/CLDN6 signaling in epithelial ovarian cancer.

Paclitaxel (PTX) resistance contributes to mortality in epithelial ovarian cancer (EOC). Aerobic glycolysis is elevated in the tumor environment and may influence resistance to PTX in EOC. KH domain-containing, RNA-binding signal transduction-associated protein 3 (KHDRBS3) is an RNA binding protein that is up-regulated in EOC, but its underlying mechanism in EOC is unclear. Here, we investigate the role of KHDRBS3 in glycolysis and increased resistance to PTX. Expression of KHDRBS3 and Claudin (CLDN6) were measured in EOC tissue and cells by quantitative real-time PCR, western blotting and immunohistochemistry. The biological functions of KHDRBS3, MIR17HG and CLDN6 were examined using MTT, colony formation, apoptosis and seahorse assays in vitro. For in vivo experiments, a xenograft model was used to investigate the effects of KHDRBS3 and MIR17HG in EOC. Here, we investigate the role of KHDRBS3 in glycolysis and increased resistance to PTX. The expression of KHDRBS3 was up-regulated in PTX-resistant cells. KHDRBS3 knockdown restrained the IC50 of PTX, cell proliferation, colony formation and glycolysis in SKOV3-R and A2780-R cells in vitro and enhanced PTX sensitivity in a xenograft mouse model in vivo. KHDRBS3 interacts with lncRNA MIR17HG, which is down-regulated in EOC tissue and cells. The effect of KHDRBS3 overexpression on PTX resistance and glycolysis was rescued by MIR17HG overexpression. Additionally, MIR17HG interacts with the 3'UTR of CLDN6 and negatively regulates CLDN6 expression. MIR17HG overexpression suppressed the IC50 of PTX and glycolysis by targeting CLDN6. Our results reveal a KHDRBS3-MIR17HG-CLDN6 regulatory axis that contributes to enhanced glycolysis in EOC and represents a potential target for therapy.

Long non-coding RNA MIR17HG sponges microRNA-21 to upregulate PTEN and regulate homoharringtonine-based chemoresistance of acute myeloid leukemia cells.

Long non-coding (lnc)RNA MIR17HG has been identified as a oncogene whose roles in acute myeloid leukemia (AML) remain unclear. The present study aimed to investigate the role of lncRNA MIR17HG in AML. Differential expression of MIR17HG in AML was determined by reverse transcription-quantitative PCR. Overexpression assays and dual luciferase reporter assays were performed to determine the relationship between MIR17HG and microRNA (miR)-21, and apoptosis was analyzed by using an apoptosis assay. The results showed that the expression of MIR17HG was decreased in AML, which was further decreased following homoharringtonine (HHT)-based chemotherapy. Bioinformatics analysis predicted that miR-21 could bind with MIR17HG. However, miR-21 overexpression had no effect on the expression level of MIR17HG. Dual luciferase reporter assays were performed to verify the direct interaction between miR-21 and MIR17HG. In addition, overexpression of MIR17HG and miR-21 in AML cell lines up- and downregulated the expression level of PTEN, respectively. Furthermore, cell apoptosis showed that MIR17HG and PTEN overexpression enhanced cell apoptosis following cell treatment with HTT. However, miR-21 overexpression exerted the opposite effect, since it reversed the effects of MIR17HG and PTEN overexpression in AML cell apoptosis. In conclusion, the current study suggested that MIR17HG could regulate the miR-21/PTEN axis to modulate the chemoresistance of AML cells.

First Patient Diagnosed as Feingold Syndrome Type 2 with Alport Syndrome and Review of the Current Literature.

Introduction: Feingold syndrome type 2 (FGLDS2) is an ultra-rare genetic disorder characterized by short stature, microcephaly, digital abnormalities, and intellectual disability. Until now, 22 patients have been reported in the literature. FGLDS2 is caused by a germline heterozygous deletion of 13q resulting in haploinsufficiency of the MIR17HG gene. Case report: In the present study, we evaluated clinical, radiological, and genetic analyses of a 10-year-old Turkish-origin girl with short stature, brachydactyly, intellectual disability, hematuria, and proteinuria. Conclusion/Discussion: In the array-CGH analysis, a 15.7-Mb deletion, arr[hg19] 13q22q31.3(78,241,132_93,967,288)×1, was detected, and this alteration was evaluated to be pathogenic. The deletion of this region covering the MIR17HG gene is a potential cause of FGLDS2. Also, at her clinical exome sequencing study, a heterozygous c.2023G>A p.(Gly675Ser) variation was detected in the COL4A5 gene (NM_000495.4) that was likely pathogenic in up-to-date databases. As a result, we report on a patient who has FGLDS2 and Alport syndrome. This is the first report of a Turkish-origin FGLDS2 patient. Reporting new cases expands the range of phenotypes, plays a crucial role in understanding the FGLDS2 pathogenesis, and is important in terms of screening at-risk family members for giving appropriate genetic counseling and preimplantation genetic diagnosis opportunities.

Association of MIR17HG and MIR155HG gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern China.

INTRODUCTION: Steroid-induced osteonecrosis of the femoral head (ONFH) is a disease of the bone. Metabolism and genetic factors are generally considered to play an important role. The purpose of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in MIR17HG and MIR155HG and the risk of steroid-induced ONFH in the population of northern China. METHODS: A total of 199 steroid-induced ONFH patients and 506 healthy controls were recruited for the study. Four SNPs of MIR17HG and seven SNPs of MIR155HG were genotyped by Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship between these SNPs and steroid-induced ONFH. RESULTS: In the codominant model, patients with the MIR17HG SNPs (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.79, p = 0.039); in the recessive model, patients with the MIR17HG SNP (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.78, p = 0.032). Stratified analysis showed that a MIR17HG SNP (rs7318578) and the MIR155HG SNPs (rs77218221, rs11911469, rs34904192 and rs4143370) were closely related to different unornamented phenotypes of steroid-induced ONFH. Analysis of the clinical indicators revealed significant differences in high-density lipoprotein (HDL-C) levels between the ONFH group and the control group (p = 0.005). In the MIR17HG SNP (rs75267932), patients with different genotypes had different levels of triglyceride (TG). The MIR155HG SNPs (rs77699734, rs1893650, and rs34904192) showed differences in triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels in patients with different genotypes. CONCLUSION: Our results confirm that MIR17HG and MIR155HG gene mutations are associated with steroid-induced ONFH susceptibility in the population of northern China, providing new evidence for the early detection and prevention of ONFH.

Epstein-Barr Virus miR-BART1-3p Regulates the miR-17-92 Cluster by Targeting E2F3.

Epstein-Barr virus (EBV) is associated with several tumors and generates BamHI A rightward transcript (BART) microRNAs (miRNAs) from BART transcript introns. These BART miRNAs are expressed at higher levels in EBV-associated epithelial malignancies than in EBV-infected B lymphomas. To test the effects of EBV miRNA on the cell cycle and cell growth, we transfected miR-BART1-3p, a highly expressed EBV-associated miRNA, into gastric carcinoma cells. We found that miR-BART1-3p induced G0/G1 arrest and suppressed cell growth in gastric carcinoma cells. As our microarray analyses showed that E2F3, a cell cycle regulator, was inhibited by EBV infection, we hypothesized that miR-BART1-3p regulates E2F3. Luciferase assays revealed that miR-BART1-3p directly targeted the 3'-UTR of E2F3 mRNA. Both E2F3 mRNA and encoded protein levels were reduced following miR-BART1-3p transfection. In contrast, E2F3 expression in AGS-EBV cells transfected with a miR-BART1-3p inhibitor was enhanced. As E2F3 has been shown to regulate the expression of highly conserved miR-17-92 clusters in vertebrates, we examined whether this expression is affected by miR-BART1-3p, which can downregulate E2F3. The expression of E2F3, miR-17-92a-1 cluster host gene (MIR17HG), and miR-17-92 cluster miRNAs was significantly reduced in EBV-associated gastric carcinoma (EBVaGC) patients compared with EBV-negative gastric carcinoma (EBVnGC) patients. Further, miR-BART1-3p as well as the siRNA specific to E2F3 inhibited the expression of the miR-17-92 cluster, while inhibition of miR-BART1-3p enhanced the expression of the miR-17-92 cluster in cultured GC cells. Our results suggest a possible role of miR-BART1-3p in cell cycle regulation and in regulation of the miR-17-92 cluster through E2F3 suppression.

MIR17HG genetic variations affect the susceptibility of IgA nephropathy in Chinese Han people.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease worldwide. It accounts for approximately 30 ~ 40% of glomerular diseases in China. However, the exact pathogenesis of IgAN is not well established. This study aimed to explore the association between MIR17HG polymorphisms and IgAN susceptibility. METHODS: Six single nucleotide polymorphisms (SNPs) of MIR17HG were genotyped in 417 patients with IgAN and 424 healthy controls. The association analysis was conducted by logistic regression adjusted for age and gender in multiple genetic models and different subgroups. RESULTS: Our results revealed that rs72640334 and rs1428 increased the susceptibility to IgAN in total populations (p < 0.05). The stratification analysis by age indicated that rs72640334 enhanced the risk of IgAN people older than 35 years, while rs7318578 played a protective role in the development of IgAN patients aged >35 years (p < 0.05). In addition, MIR17HG-rs72640334 could facilitate the occurrence of IgAN in females (p < 0.05). In Lee's grade III-Vsubgroup, rs72640334 and rs7336610 have an increasing effect on IgAN risk, while rs7318578 has a decreasing effect on IgAN susceptibility (p < 0.05). CONCLUSIONS: Our findings suggested that MIR17HG genetic polymorphisms were correlated with IgAN susceptibility. It provided new evidence for the potential molecular mechanism of IgAN and may serve as a new biomarker for the treatment and early diagnosis of IgAN.

Feingold syndrome type 2 in a patient from China.

Feingold syndrome type 2 (FGLDS2, MIM614326) is a genetic congenital malformation syndrome, caused by germline heterozygous deletion of MIR17HG on chromosome 13q31, which is extremely rare worldwide. To date, less than 25 patients have been described in the literature. Here, we report on a 3-year-old girl presented with hip dysplasia, polysyndactyly of the left thumb, brachymesophalangy of the fifth digit, microcephaly, intellectual disability, and growth delay. This is likely to be the first case of Feingold syndrome type 2 ever discovered among Chinese population. Through genetic testing and pedigree analysis, she was identified to have a de novo 4.8-Mb microdeletion at chromosome 13q31.3-q32.1, encompassing MIR17HG, GPC5, and GPC6. Additionally, we detected two common compound heterozygous variants (c.919-2A>G and c.147C>G) in SLC26A4 encoding pendrin protein, as well as a novel heterozygous variant c.985_988del in COMP encoding cartilage oligomeric matrix protein. This case report aims to analyze the microdeletion and the three types of variant detected in the patient, and to explore the association between the genotype and phenotype in patients with Feingold syndrome type 2, which may contribute to further understanding and future diagnosis of this disorder.

Genetic variants in MIR17HG affect the susceptibility and prognosis of glioma in a Chinese Han population.

BACKGROUND: lncRNA MIR17HG was upregulated in glioma, and participated in promoting proliferation, migration and invasion of glioma. However, the role of MIR17HG polymorphisms in the occurrence and prognosis of glioma is still unclear. METHODS: In the study, 592 glioma patients and 502 control subjects were recruited. Agena MassARRAY platform was used to detect the genotype of MIR17HG polymorphisms. Logistic regression analysis was used to evaluate the relationship between MIR17HG single nucleotide polymorphisms (SNPs) and glioma risk by odds ratio (OR) and 95% confidence intervals (CIs). Kaplan-Meier curves, Cox hazards models were performed for assessing the role of these SNPs in glioma prognosis by hazard ratios (HR) and 95% CIs. RESULTS: We found that rs7318578 (OR = 2.25, p = 3.18 × 10- 5) was significantly associated with glioma susceptibility in the overall participants. In the subgroup with age <  40 years, rs17735387 (OR = 1.53, p = 9.05 × 10- 3) and rs7336610 (OR = 1.35, p = 0.016) were related to the higher glioma susceptibility. More importantly, rs17735387 (HR = 0.82, log-rank p = 0.026) were associated with the longer survival of glioma patients. The GA genotype of rs17735387 had a better overall survival (HR = 0.75, log-rank p = 0.013) and progression free survival (HR = 0.73, log-rank p = 0.032) in patients with I-II glioma. We also found that rs72640334 was related to the poor prognosis (HR = 1.49, Log-rank p = 0.035) in female patients. In the subgroup of patients with age ≥ 40 years, rs17735387 was associated with a better prognosis (HR = 0.036, Log-rank p = 0.002). CONCLUSION: Our study firstly reported that MIR17HG rs7318578 was a risk factor for glioma susceptibility and rs17735387 was associated with the longer survival of glioma among Chinese Han population, which might help to enhance the understanding of MIR17HG gene in gliomagenesis. In subsequent studies, we will continue to collect samples and follow up to further validate our findings and further explore the function of these MIR17HG SNPs in glioma in a larger sample size.

Association of microRNA 17 host gene variant (rs4284505) with susceptibility and severity of systemic lupus erythematosus.

OBJECTIVE: MicroRNAs are large family clusters of small noncoding RNAs that implicated in genetic and epigenetic regulation of several immunological processes and pathways. As an epigenetic modifier, the microRNA 17-92 cluster host gene (MIR17HG) has been shown to regulate the expression of genes involved in systemic lupus erythematosus (SLE) pathway. This study aimed to explore the association of MIR17HG (rs4284505; A>G) variant with SLE development and phenotype in a sample of the Eastern Mediterranean population. METHODS: A total of 326 participants (163 patients with SLE and 163 healthy controls) were enrolled in this study. The different genotypes of the MIR17HG (rs4284505) variant were characterized using the TaqMan real-time polymerase chain reaction technique. Association with the available clinical and laboratory data, including the systemic lupus erythematosus disease activity index (SLEDAI), was also executed. RESULTS: The MIR17HG (rs4284505) variant showed a protective effect against developing SLE under heterozygote (A/G vs A/A; odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.05-0.20, P < 0.001) and dominant (A/G+G/G vs A/A; OR = 0.39, 95% CI = 0.25-0.61, P < .001) models. This association was consistent even after SLE stratified by lupus nephritis. In contrast, rs4284505 (G/G) genotype conferred increased susceptibility to SLE (G/G vs A/A+A/G; OR = 2.15, 95% CI = 1.31-3.53, P = .002). Moreover, the rs4284505 variant showed a statistically significant association with mucocutaneous lesions and SLEDAI scores (all P < .05). CONCLUSION: This study is the first one to explore that the MIR17HG rs4284505 is associated with SLE risk; (A/G) genotype conferred a protective effect, while the (G/G) genotype showed increased susceptibility to SLE and association with the disease severity in the study population.

MIR17HG polymorphism (rs7318578) is associated with liver cancer risk in the Chinese Han population.

Numerous evidence has revealed that single-nucleotide polymorphisms (SNPs) are associated with liver cancer risk. To assess whether the MIR17HG polymorphisms are associated with the liver cancer risk in the Chinese Han population, we performed a case-control (432 liver cancer patients and 430 healthy controls) study. Genotyping of four variants of MIR17HG was performed with the Agena MassARRAY platform. We used χ2 test to compare the distribution of SNPs allele and genotypes frequencies of cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the association under genetic models. The results indicated that the rs7318578 was significantly associated with increased the risk of liver cancer in the allele (OR = 1.45, 95% CI: 1.18-1.77, P=3.04E-04), recessive (OR = 3.69, 95% CI: 2.45-5.56, P=4.52E-10) and additive model (OR = 1.35, 95% CI: 1.13-1.62, P=0.001). Moreover, we found that individuals with the genotype CC of rs7318578 presented with an increased risk of liver cancer (OR = 3.03, 95% CI: 1.98-4.65, P=3.83E-07); however, the CA genotype of rs7318578 significantly decreased the risk of liver cancer (OR = 0.61, 95% CI: 0.45-0.83, P=0.001, compared with those with the AA genotype. Our findings indicated that MIR17HG polymorphism (rs7318578) contributes to liver cancer susceptibility to the Chinese Han population. Further studies with larger samples are required to confirm the results, as well as functional studies to determine the role of this SNP in miRNA expression or molecular pathways.