Diagnostic and prognostic significance of long noncoding RNA LINC00173 in patients with melanoma

SUMMARY OBJECTIVE: A growing volume of literature has suggested long noncoding RNAs (lncRNAs) as important players in tumor progression. In this study, we aimed to investigate the expression and prognostic value of lncRNA LINC00173 (LINC00173) in melanoma. METHODS: LINC00173 expression was measured in 163 paired cancerous and noncancerous specimen samples by real-time polymerase chain reaction. The correlations between LINC00173 expression with clinicopathological characteristics and prognosis were analyzed by chi-square test, log-rank test, and multivariate survival analysis. Receiver-operating characteristic curves were used for the assessment of the diagnostic value of LINC00173 for melanoma patients. RESULTS: The expression level of LINC00173 in melanoma specimens was distinctly higher than that in adjacent non-neoplasm specimens (p<0.01). Besides, LINC00173 was expressed more frequently in patients with advanced melanoma than in patients with early melanoma. Multivariate assays confirmed that LINC00173 expression level was an independent prognostic predictor of melanoma patients (p<0.05). CONCLUSION: Our data indicated that LINC00173 expression could serve as an unfavorable prognostic biomarker for melanoma patients.

Effects of long-chain noncoding RNA Linc00673 overexpression on proliferation and apoptosis of gastric cancer cell line MGC-803 / 中国应用生理学杂志

Objective: To investigate the effects of long-chain noncoding RNA Linc00673 overexpression on proliferation and apoptosis of gastric cancer cells and its mechanisms. Methods: The recombinant lentivirus expressing plasmid pLVX-Linc00673 and the control empty plasmid pLVX-NC were packaged and amplified in 293T cells, and the recombinant lentivirus was transfected into gastric cancer cell line MGC-803 to establish a cell line stably overexpressing Linc00673. The expression of Linc00673 gene was detected by real-time fluorescence quantitative PCR. The growth and proliferation of cells were observed by MTT assay and clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. The expressions of cell cycle related regulatory genes were detected by qPCR. The expressions of key molecules in the PI3K/Akt signaling pathway and tumor proliferation related proteins were detected by Western blot. Results: The expressions of Linc00673 in gastric cancer cell line MGC-803, BGC-823 and AGS were significantly higher than that in normal gastric mucosa cell line GES-1 (P＜0.05). MGC-803 cell line with stable overexpression of LINC00673 was established, and the expression level of LincC00673 was 200 times higher than that of the control empty carrier group. Overexpression of Linc00673 promoted proliferation of MGC-803 cells (P＜0.05) and clone formation (P＜0.05), inhibited cell apoptosis and affected the G1→S phase progression of cell cycle (P＜0.01). Overexpression of Linc00673 could affect the expressions of cell cycle regulatory gene CCNG2, P19 and CDK1 in MGC-803. Western blot showed that Linc00673 overexpression not only promoted the expressions of the key molecule pAkt in PI3K / Akt signaling pathway and its downstream target NF-κ B and Bcl-2 protein, but also up regulated the expressions of tumor related factors β-catenin and EZH2 proteins. Conclusion: Overexpression of Linc00673 may promote proliferation and inhibit apoptosis of MGC-803 cells through PI3K/Akt signaling pathway.

Differential Expression of Long Non-coding RNA Cancer Susceptibility Candidate 2 and Imprinted Gene H19 in Extrahepatic Cholangiocarcinoma / 中国医学科学院学报

Objective To investigate the expression and the potential roles of long non-coding RNA(lncRNA)cancer susceptibility candidate 2(CASC2)and imprinted gene H19 in extrahepatic cholangiocarcinoma(ECC). Methods Four samples from patients with ECC were collected for high-throughput sequencing which was conducted to reveal the transcriptomic profiles of lncRNA CASC2 and H19.Bioinformatics tools were employed to predict the potential roles of the two genes.Another 22 ECC tissue samples and the cholangiocarcinoma cell lines(RBE,QBC939,HuH-28,and HuCCT1)with different degrees of differentiation were selected for validation.The para-carcinoma tissue and normal human intrahepatic biliary epithelial cell(HIBEC)were used as the control groups.The expression levels of lncRNA CASC2 and H19 in carcinoma tissue,para-carcinoma tissue,and cell lines were determined by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation analysis was carried out for the clinical indicators of patients with the expression levels of the target genes. Results The two target genes showed significantly different expression between carcinoma tissue and para-carcinoma tissue(all P<0.05).Specifically,CASC2 had higher expression level in the carcinoma tissue than in the para-carcinoma tissue(t=1.262,P=0.025),whereas the expression of H19 showed an opposite trend(t=1.285,P=0.005).The expression levels of CASC2 in QBC939(t=8.114,P=0.015)and HuH-28(t=9.202,P=0.012)cells were significantly higher than that in the control group.The expression levels of H19 were significantly lower in RBE(t=-10.244,P<0.001),QBC939(t=-10.476,P<0.001),HuH-28(t=-19.798,P<0.001),and HuCCT1(t=-16.193,P=0.004)cells than in the control group.Bioinformatics analysis showed that CASC2 was mainly involved in the metabolic process and H19 in the development of multicellular organisms.Both CASC2 and H19 were related to catalytic activity.The expression level of lncRNA CASC2 was correlated with pathological differentiation(χ 2=6.222,P=0.022)and lymph node metastasis(χ2=5.455,P=0.020),and that of lncRNA H19 with pathological differentiation(χ2=1.174,P=0.029)and tumor size(χ2=-0.507,P=0.037). Conclusions In the case of ECC,lncRNA CASC2 and H19 have transcription disorders.lncRNA CASC2 is generally up-regulated in the carcinoma tissue,while H19 is down-regulated.Both genes have the potential to become new molecular markers for ECC.

ZNF750 facilitates carcinogenesis via promoting the expression of long non-coding RNA CYTOR and influences pharmacotherapy response in colon adenocarcinoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The epidermal cell differentiation regulator zinc finger protein 750 (ZNF750) is a transcription factor containing the Cys2His2 (C2H2) domain, the zinc finger structure of which is located at the N-terminal 25‍‍-‍46 amino acids of ZNF750. It can promote the expression of differentiation-related factors while inhibiting the expression of progenitor cell-related genes. ZNF750 is directly regulated by p63 (encoded by the TP63 gene, belonging to the TP53 superfamily). The Krüppel-like factor 4 (KLF4), repressor element-1 (RE-1)‍-silencing transcription factor (REST) corepressor 1 (RCOR1), lysine demethylase 1A (KDM1A), and C-terminal-binding protein 1/2 (CTBP1/2) chromatin regulators cooperate with ZNF750 to repress epidermal progenitor genes and activate the expression of epidermal terminal differentiation genes (Sen et al., 2012; Boxer et al., 2014). Besides, ZNF750 and the regulatory network composed of bone morphogenetic protein (BMP) signaling pathway, long non-coding RNAs (lncRNAs) (anti-differentiation non-coding RNA (ANCR) and tissue differentiation-inducing non-protein coding RNA (TINCR)), musculoaponeurotic fibrosarcoma oncogene (MAF)/MAF family B (MAFB), grainy head-like 3 (GRHL3), and positive regulatory domain zinc finger protein 1 (PRDM1) jointly promote epidermal cell differentiation (Sen et al., 2012).

Expression, functional mechanism and therapy application of long noncoding RNA in β-thalassemia / 中南大学学报(医学版)

β-thalassemia (β-thal) is one of the most common genetic diseases in the world, its pathogenesis is extremely complex and there is no effective treatment at present. The birth of children with moderate and severe β-thal brings economic pressure to families, social medical and health services. Long noncoding RNA (lncRNA) is a type of noncoding protein transcripts with a length greater than 200 nucleotides, which is involved in a variety of biological processes, such as cell proliferation, differentiation and chromosome variation and plays an important role in the epigenetic and post-transcriptional regulation of genes. It has potential value in the diagnosis, prevention and treatment of β-thal. LncRNA possesses the characteristics such as tissue specificity, cell specificity, developmental stage specificity, space-time specificity and disease specificity, and its complex interaction network has become a challenge to translate research results into clinical practice. Taking lncRNA as an entry point, in-depth understanding of the function of lncRNA in β-thal and explanation of its related regulatory mechanisms will provide theoretical basis for targeting treatment of β-thal, which can improve the diagnosis and treatment of β-thal.

The single nucleotide polymorphism rs1814521 in long non-coding RNA ADGRG3 associates with the susceptibility to silicosis: a multi-stage study

BACKGROUND@#This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis.@*METHODS@#First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system.@*RESULTS@#A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011).@*CONCLUSION@#The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.

LINC00668 is Highly Expressed in Lung Squamous Cell Carcinoma and Promotes Tumor Cell Migration and Invasion / 中国肺癌杂志

BACKGROUND@#A lack of effective treatment for lung squamous cell carcinoma (LUSC) makes it an important factor restricting the 5-year survival rate of non-small cell lung cancer (NSCLC). Long non-coding RNA 00668 (LINC00668) was reported to play crucial regulatory roles in the tumorigenesis and progression of various cancers; however, its role in LUSC is unclear. The aim of this study was to investigate the prognosis value and biological function of LINC00668 in NSCLC, especially in LUSC.@*METHODS@#The expression pattern of LINC00668 and its relationship with clinical characteristics and prognosis of patients were investigated in the NSCLC especially LUSC based on The Cancer Genome Altas (TCGA) database. Its function in LUSC cells was explored in vitro.@*RESULTS@#LINC00668 expression was significantly up-regulated in LUSC patients and high expression level of LINC00668 was associated with advanced tumor-node-metastasis (TMN) stage. Moreover, the expression of LINC00668 significantly increased in smoking patients, and was a prognostic indicator for overall survival (OS) of smoking patients with LUSC. In vitro experiments showed that LINC00668 has significantly higher expression level in LUSC cell lines and tissues compared to normal bronchial epithelial cell and para-tumor tissues; meanwhile, functional assay indicated knockdown of LINC00668 effectively inhibited the migration and invasion of LUSC cells.@*CONCLUSIONS@#LINC00668 might closely relate to the development of LUSC, and inhibition of LINC00668 may reduce the metastasis of LUSC.

Clinical Significance of Low Expression of LncRNA CASC15 in Acute Myeloid Leukemia with NPM1 Mutations / 中国实验血液学杂志

AbstractObjective: To identify the expression and methylation patterns of lncRNA CASC15 in bone marrow (BM) samples of acute myeloid leukemia (AML) patients, and further explore its clinical significance.@*METHODS@#Eighty-two de novo AML patients and 18 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the expression and methylation data of CASC15. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of CASC15 expression to identify AML. The patients were divided into CASC15high group and CASC15low group by X-tile method, and the prognostic value of CASC15 was identified by Kaplan-Meier method and univariate and multivariate Cox regression analysis.@*RESULTS@#The expression level of CASC15 was significantly decreased in BM cells of AML patients compared with healthy donors (P<0.001). ROC curve analysis suggested that CASC15 expression might be a potential biomarker to discriminate AML from controls. The expression of CASC15 was high at the early stage of hematopoiesis, and reached a peak at the stage of multipotent progenitors differentiation, then decreased rapidly, and was at a range of low level fluctuations in the subsequent process. Among FAB subtypes, CASC15 expression in M0 was significantly higher than that in M1-M7. Clinically, CASC15low patients were more likely to have NPM1 mutations than CASC15high patients (P=0.048), while CASC15high patients had a significantly higher frequency of IDH1 and RUNX1 mutations (P=0.021 and 0.014, respectively). Moreover, CASC15low group had a shorter overall survival (OS) in patients with NPM1 mutations. Furthermore, multivariate analysis confirmed that CASC15 expression was a significant independent risk factor for OS in NPM1 mutated AML patients. In addition, CASC15 methylation level in BM samples of AML patients was significantly decreased compared with healthy donors. Patients with CASC15 high methylation had poor OS and disease-free survival.@*CONCLUSION@#The expression of CASC15 is decreased in AML, and low CASC15 expression may predict adverse prognosis in AML patients with NPM1 mutations. Moreover, CASC15 methylation level in AML is significantly decreased, and high CASC15 methylation may predict poor prognosis in AML.

Pan-cancer analysis of the expression pattern of long non-coding RNA MIR22HG / 南方医科大学学报

OBJECTIVE@#To conduct a pan-cancer analysis of the expression of long non-coding RNA (lncRNA) MIR22HG and explore its association with clinical characteristics.@*METHODS@#We analyzed the expression of MIR22HG in different tumors and its association with clinical staging, lymph node metastasis, tumor mutation burden (TMB) and microsatellite instability (MSI) using R package based on the Cancer Genome Atlas (TCGA) datasets. The relationship between MIR22HG expression and infiltrating immune cells was analyzed using TIMER algorithm. The association of MIR22HG gene alteration frequency with the clinical outcomes was examined using cBioPortal online software. Data form Genomics of Drug Sensitivity in Cancer (GDSC) were used to analyze the relationship between MIR22HG and the sensitivity of chemotherapy drugs. We specifically analyzed MIR22HG expression in hepatocellular carcinoma (HCC) and its correlation with sorafenib treatment using GEO database and verified the results in 12 pairs of HCC specimens. Kaplan-Meier analysis was performed to analyze the correlation of MIR22HG with the outcomes of sorafenib treatment. We also tested the effects of MIR22HG overexpression and knockdown on IC50 of sorafenib in HCC cells.@*RESULTS@#MIR22HG was downregulated in most tumors (P < 0.05), where its deletion mutations were frequent, and associated with a poor prognosis (P < 0.05). In many tumors, MIR22HG expression level was correlated with clinical stage, lymph node metastasis, TMB, MSI, immune cell infiltration, immune checkpoint-related genes, and sensitivity to common chemotherapeutic drugs (P < 0.05). Among the 6 common infiltrating immune cells in cancers, neutrophil infiltration had the strongest correlation with MIR22HG expression level, especially in breast cancer, rectal cancer and kidney renal papillary cell carcinoma (P < 0.05). MIR22HG was downregulated in HCC in association with HCC progression (P < 0.05). In HCC patients, a low MIR22HG expression was associated with a favorable outcome after sorafenib treatment (HR=2.94, P=0.075) and was capable of predicting the response to sorafenib treatment (AUC=0.8095). Compared with the negative control, MIR22HG overexpression obviously reduced sorafenib sensitivity (with IC50 of 7.731 vs 15.61) while MIR22HG knockdown increased sorafenib sensitivity of HCC cells (with IC50 of 7.986 vs 5.085).@*CONCLUSION@#MIR22HG expression level is correlated with clinical stage, lymph node metastasis, TMB, MSI, immune cell infiltration, and chemosensitivity in most cancer, suggesting its potential as an immunotherapeutic target and also a prognostic biomarker for tumors.

Knockdown of long non-coding RNA MIR4697 host gene inhibits adipogenic differentiation in bone marrow mesenchymal stem cells / 北京大学学报(医学版)

OBJECTIVE@#To preliminarily investigate the role of long non-coding RNA (lncRNA) MIR4697 host gene (MIR4697HG) in regulating the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).@*METHODS@#For adipogenic differentiation, BMSCs were induced in adipogenic media for 10 days. The mRNA expression levels of lncRNA MIR4697HG and adipogenic marker genes including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhanced binding protein α (CEBP/α) and adiponectin (ADIPQ) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) at different time points (0, 1, 2, 3, 5, 7, 10 days). The MIR4697HG stable knockdown-BMSC cell line was generated by infection of MIR4697HG shRNA-containing lentiviruses. To avoid off-target effect, two target sequences (shMIR4697HG-1, shMIR4697HG-2) were designed. And then cells were induced to differentiate in adipogenic medium. Oil red O staining, Western blot and qRT-PCR were used to detect the effect of MIR4697HG knockdown on adipogenic differentiation of BMSCs.@*RESULTS@#The mRNA expression level of MIR4697HG was significantly increased during adipogenic differentiation (P < 0.01), and adipogenic differentiation of BMSCs was evidenced by upregulated mRNA levels of specific adipogenesis-related genes including PPARγ, CEBP/α and ADIPQ. Observed by fluorescence microscopy, more than 90% transfected target cells expressed green fluorescent protein successfully after shMIR4697HG-1 group, shMIR4697HG-2 group and shNC group transfection for 72 h. And the transfection efficiency of MIR4697HG examined by qRT-PCR was above 60%. Then the BMSCs were treated with adipogenic media for 7 days and showed that the mRNA expression levels of adipogenesis-related genes including PPARγ, CEBP/α and ADIPQ were significantly decreased in the MIR4697HG knockdown group (P < 0.01), while the expression levels of PPARγ and CEBP/α proteins were decreased remarkably as well (P < 0.01). Consistently, MIR4697HG knockdown BMSCs formed less lipid droplets compared with the control BMSCs, which further demonstrated that MIR4697HG knockdown inhibited adipogenic differentiation of BMSCs.@*CONCLUSION@#lncRNA MIR4697HG played a crucial role in regulating the adipogenic differentiation of BMSCs, and MIR4697HG knockdown significantly inhibited the adipogenic differentiation of BMSCs. These data may suggest that lncRNA MIR4697HG could serve as a therapeutic potential target for the aberrant adipogenic differentiation-associated disorders including osteoporosis.

Research progress on the regulatory mechanism of non-coding RNA in arsenic toxicity / 中华劳动卫生职业病杂志

Arsenic is a non-metallic element, and the International Agency for Research on Cancer has identified arsenic and its compounds as carcinogens. Arsenic and its compounds can be absorbed through the respiratory tract, skin and digestive tract, distributed in the liver, kidney, lung and skin, and cause damage. Non-coding RNAs are closely related to arsenic-induced nervous system disorders, cell necrosis, reproductive toxicity, and carcinogenesis. In recent years, the network regulation of microRNAs (miRNAs) , long non-coding RNAs (lncRNAs) , and circular RNAs (circRNAs) among non-coding RNAs in various diseases induced by arsenic has become a new research field. This paper summarizes the existing scientific research results, and expounds the mechanism of miRNAs, lncRNAs and circRNAs in arsenic toxicity, and provides basic data and theoretical basis for the prevention and treatment of arsenic poisoning.

Research progress on the role of lncRNA in the occurrence and development of malignant mesothelioma / 中华劳动卫生职业病杂志

Malignant mesothelioma (MM) is a long latency, poor prognosis and asbestos exposure related malignant disease. Long non-coding RNA (lncRNA) is a kind of RNA with a length of more than 200 nucleotides that does not encode protein. It plays an important role in epigenetic regulation, cell cycle regulation and cell differentiation regulation. Recent studies have shown that the abnormal expression or function of lncRNA is closely related to the diagnosis and prognosis of MM. In this paper, the lncRNA research on MM is reviewed to better understand the role of lncRNA in MM.

Long non-coding RNA LOC101927476 inhibits invasion, migration, and proliferation of ovarian cancer cell lines / 中华肿瘤杂志

Objective: To investigate the expression of long non-coding RNA LOC101927476 (LncRNA LOC101927476) in ovarian cancer and its effect on the biological characteristics of ovarian cancer. Methods: Patients with ovarian cancer who underwent surgery in Cancer Hospital of Chinese Academy of Medical Sciences from 2018 to 2019 were selected. The expressions of LOC101927476 in ovarian cancer cells 3AO, OVCA429, TOV21G, A2780, SKOV3, as well as 22 primary tumor tissues and their matched metastatic tumor tissues were detected by real-time quantitative polymerase chain reaction (RT-PCR). Ovarian cancer transcriptome sequencing data from the TCGA database was used to verify the expressions of LOC101927476 and GATA4. 3AO and OVCA429 cells were infected with lentivirus plasmid containing OE-LOC101927476 and single guide RNA (sg-RNA) targeting LOC101927476, respectively. The effects of LOC101927476 on migration and invasion were detected by Transwell and wound healing assay. The effect of LOC101927476 on cell proliferation was detected by cell counting kit-8 (CCK-8) assay. Results: RT-PCR assay showed that 20 out of 22 patients had significantly lower expression of LOC101927476 in their metastatic tumors compared with primary tumors. Transwell assay showed that overexpression of LOC101927476 significantly inhibited the invasion and migration capacities of 3AO cells. The numbers of invading and migrating 3AO cells infected with OE-LOC101927476 lentivirus were (357±63) and (699±65), respectively, lower than (661±95) and (1 024±76) in OE-EV group (P<0.050). In contrast, the numbers of invading and migrating OVCA429 cells with LOC101927476 knockdown were (512±72) and (472±40), respectively, higher than (309±13) and (363±27) in sg-Control group (P<0.050). Wound healing assay results showed that after 48 hours, the percentage of scratch healing of 3AO cells in OE-LOC101927476 group was (10.86±0.63)%, significantly lower than (57.38±4.42)% of OE-EV group (P=0.009). After 24 hours, the percentage of scratch healing of OCVA429 cells in sg-LOC101927476 group was (59.98±1.34)%, significantly higher than (23.15±2.03)% of sg-Control group (P=0.004). CCK-8 assays showed that the OD value of 3AO cells in OE-LOC101927476 group was (2.07±0.08), significantly lower than (2.29±0.04) of OE-EV group (P=0.009). The OD value of OVCA429 cells in sg-LOC101927476 group was (2.13±0.03), significantly higher than (1.93±0.03) of sg-Control group (P=0.001). The relative expression of GATA4 in OE-LOC101927476 group was (1.86±0.25), significantly higher than 1.00 of OE-EV group (P=0.001). In patients with high expression of LncRNA LOC101927476, the expression level of GATA4 was (2.93±0.35), which was higher than (0.29±0.06) of LOC101927476 low expression group (P=0.001). Conclusion: LncRNA LOC101927476 can inhibit the invasion, migration and proliferation of ovarian cancer cells.

Role and mechanism of non-coding RNA in the pathogenesis of acute kidney injury / 生理学报

Acute kidney injury (AKI) is a common clinical syndrome and an independent risk factor of chronic kidney disease and end-stage renal failure. At present, the treatments of AKI are still very limited and the morbidity and mortality of AKI are rising. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs (circRNAs), are RNAs that are transcribed from the genome, but not translated into proteins. It has been widely reported that ncRNA is involved in AKI caused by ischemia reperfusion injury (IRI), drugs and sepsis through different molecular biological mechanisms, such as apoptosis and oxidative stress response. Therefore, ncRNAs are expected to become a new target for clinical prevention and treatment of AKI and a new biomarker for early warning of the occurrence and prognosis of AKI. Here, the role and mechanism of ncRNA in AKI and the research progress of ncRNA as biomarkers are reviewed.

Exploring the expression profile of vitamin D receptor and its related long non-coding RNAs in patients with acute lymphoblastic leukemia

SUMMARY OBJECTIVE: Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Previous studies have indicated the involvement of vitamin D receptor (VDR) and related long noncoding RNAs (lncRNAs) signaling in the pathophysiology of several cancers. However, their contribution to ALL remains to be elucidated. METHODS: In this case-control study, 30 patients with newly diagnosed ALL and 30 age- and sex-matched healthy children were selected. Then, the level of 25(OH) vitamin D and the expression of VDR and four VDR-related lncRNAs were assessed. RESULTS: No significant difference in serum 25(OH) vitamin D was observed between patients with ALL (20.42±6.5 ng/mL) and healthy subjects (25.45±11 ng/mL). In addition, the expression of MALAT-1, HOTAIR, and P-21 was not statistically significant between the two groups. However, a significant reduction in VDR and H19 expression was observed in patients with ALL (p<0.05). CONCLUSIONS: 25(OH) vitamin D insufficiency was evident in both groups. VDR and H19 signaling might be contributed to the pathogenesis of ALL, which needs further investigations.

A novel lncRNA-mRNA-miRNA signature predicts recurrence and disease-free survival in cervical cancer

Cervical cancer (CC) patients have a poor prognosis due to the high recurrence rate. However, there are still no effective molecular signatures to predict the recurrence and survival rates for CC patients. Here, we aimed to identify a novel signature based on three types of RNAs [messenger RNA (mRNAs), microRNA (miRNAs), and long non-coding RNAs (lncRNAs)]. A total of 763 differentially expressed mRNAs (DEMs), 46 lncRNAs (DELs), and 22 miRNAs (DEMis) were identified between recurrent and non-recurrent CC patients using the datasets collected from the Gene Expression Omnibus (GSE44001; training) and The Cancer Genome Atlas (RNA- and miRNA-sequencing; testing) databases. A competing endogenous RNA network was constructed based on 23 DELs, 15 DEMis, and 426 DEMs, in which 15 DELs, 13 DEMis, and 390 DEMs were significantly associated with disease-free survival (DFS). A prognostic signature, containing two DELs (CD27-AS1, LINC00683), three DEMis (hsa-miR-146b, hsa-miR-1238, hsa-miR-4648), and seven DEMs (ARMC7, ATRX, FBLN5, GHR, MYLIP, OXCT1, RAB39A), was developed after LASSO analysis. The built risk score could effectively separate the recurrence rate and DFS of patients in the high- and low-risk groups. The accuracy of this risk score model for DFS prediction was better than that of the FIGO (International Federation of Gynecology and Obstetrics) staging (the area under receiver operating characteristic curve: training, 0.954 vs 0.501; testing, 0.882 vs 0.656; and C-index: training, 0.855 vs 0.539; testing, 0.711 vs 0.508). In conclusion, the high predictive accuracy of our signature for DFS indicated its potential clinical application value for CC patients.

Long non-coding ribonucleic acid H19 and ten-eleven translocation enzyme 1 messenger RNA expression levels in uterine fibroids may predict their postoperative recurrence

OBJECTIVES: To investigate the predictive value of long non-coding RNA (lncRNA) H19 and the ten-eleven translocation enzyme 1 (TET1) transcriptional expression in postoperative recurrence of uterine fibroids (UFs). METHODS: Seventy-five patients with UF, who underwent surgical treatment, were enrolled in the treatment group, and 60 healthy individuals were enrolled in the control group. The relative expression levels of lncRNA H19 and TET1 mRNA in the serum and UF tissues were analyzed. The patients were further divided into a better curative (BC) group and a poor efficacy (PE) group to analyze the predictive value of lncRNA H19 and TET1 and the independent risk factors affecting the recurrence of UF. RESULTS: Compared with the control group, lncRNA H19 expression levels were significantly higher, while TET1 expression levels were significantly lower in the treatment group (p<0.001). The area under the receiver operating characteristic (ROC) curve (AUC) values of the two indicators for diagnostic importance were found to be 0.872 and 0.826, respectively. Compared with the PE group, lncRNA H19 expression levels were significantly lower, while TET1 expression levels were significantly higher in the BC group (p<0.001). The AUC values of the two indicators for their predictive efficacy were 0.788 and 0.812, respectively. Logistic regression analysis showed that age, menarche age, maximum diameter of UFs, number of UFs, lncRNA H19 levels, and TET1 levels were independent risk factors affecting UF recurrence. The AUC values of lncRNA H19 and TET1 for their predictive value for postoperative recurrence were 0.814 and 0.765, respectively. CONCLUSIONS: The lncRNA H19 and TET1 have high diagnostic and predictive efficacy for determining the postoperative recurrence of UFs.

Knockdown of lncRNA H19 suppresses endometriosis in vivo

The long noncoding RNA (lncRNA) H19 is involved in the pathogenesis of endometriosis by modulating the proliferation and invasion of ectopic endometrial cells in vitro, but related in vivo studies are rare. This study aimed to investigate the role of lncRNA H19 in a nude mouse model of endometriosis. Ectopic endometrial stromal cells (ecESCs) were isolated from ectopic endometrium of patients with endometriosis and infected with lentiviruses expressing short hairpin RNA (shRNA) negative control (LV-NC-shRNA) or lncRNA-H19 shRNA (LV-H19-shRNA). The ecESCs infected with LV-NC-shRNA and LV-H19-shRNA were subcutaneously implanted into forty 6- to 8-week-old female nude mice. The size and weight of the endometriotic implants were measured at 1, 2, 3, and 4 weeks after implantation and compared, and lncRNA H19 levels in endometriotic implants were evaluated using real-time polymerase chain reaction (RT-PCR). All nude mice survived the experimental period, and no significant differences in body weight were observed between the experimental group and the control group. All nude mice developed histologically confirmed subcutaneous endometriotic lesions with glandular structures and stroma after 1 week of implantation. The subcutaneous lesions in the LV-NC-shRNA group after 1, 2, 3, and 4 weeks of implantation were larger than those in the LV-H19-shRNA group, and lncRNA H19 levels in subcutaneous lesions in the LV-NC-shRNA group were significantly higher than those in the LV-H19-shRNA group. Knockdown of lncRNA H19 suppresses endometriosis in vivo. Further study is required to explore the underlying mechanism in the future.

Down-regulation of HCP5 inhibits cell proliferation, migration, and invasion through regulating EPHA7 by competitively binding miR-101 in osteosarcoma

Patients with osteosarcoma (OS) usually have poor overall survival because of frequent metastasis. Long non-coding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and metastasis. In this study, we investigated the expression and roles of lncRNA human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in OS, aiming to provide a novel molecular mechanism for OS. HCP5 was up-regulated both in OS tissues and cell lines and high expression of HCP5 was associated to low survival in OS patients. Down-regulation of HCP5 inhibited cell proliferation, migration, and invasion, suggesting its carcinogenic role in OS. miR-101 was targeted by HCP5 and its expression was decreased in OS. The inhibitor of miR-101 reversed the impact of HCP5 down-regulation on cell proliferation, apoptosis, and metastasis in OS. Ephrin receptor 7 (EPHA7) was proved to be a target of miR-101 and had ability to recover the effects of miR-101 inhibitor in OS. In conclusion, lncRNA HCP5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis through depleting the expression of EPHA7 by binding to miR-101, providing a potential therapeutic strategy of HCP5 in OS.