Value Of Long Non-coding RNAs Research Articles

Prognostic value and immune infiltration of novel signatures in colon cancer microenvironment

BackgroundGrowing evidence has shown that the prognosis for colon cancer depends on changes in microenvironment. The purpose of this study was to elucidate the prognostic value of long noncoding RNAs (lncRNAs) related to immune microenvironment (IM) in colon cancer.MethodsSingle sample gene set enrichment analysis (ssGSEA) was used to identify the subtypes of colon cancer based on the immune genomes of 29 immune signatures. Cox regression analysis identified a lncRNA signatures associated with immune infiltration. The Tumor Immune Estimation Resource database was used to analyze immune cell content.ResultsColon cancer samples were divided into three subtypes by unsupervised cluster analysis. Cox regression analysis identified an immune infiltration-related 5-lncRNA signature. This signature combined with clinical factors can effectively improve the predictive ability for the overall survival (OS) of colon cancer. At the same time, we found that the expression of H19 affects the content of B cells and macrophages in the microenvironment of colon cancer and affects the prognosis of colon cancer. Finally, we constructed the H19 regulatory network and further analyzed the possible mechanisms. We found that knocking down the expression of H19 can significantly inhibit the expression of CCND1 and VEGFA. At the same time, the immunohistochemical assay found that the expression of CCND1 and VEGFA protein was significantly positively correlated with the infiltration of M2 type macrophages.ConclusionThe findings may help to formulate clinical strategies and understand the underlying mechanisms of H19 regulation. H19 may be a biomarker for targeted treatment of colon cancer.

Identification of a nomogram based on an 8-lncRNA signature as a novel diagnostic biomarker for childhood acute lymphoblastic leukemia.

Childhood acute lymphoblastic leukemia (cALL) still represents a major cause of disease-related death in children. This study aimed to explore the prognostic value of long non-coding RNAs (lncRNAs) in cALL. We downloaded lncRNA expression profiles from the TARGET and GEO databases. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to identify lncRNA-based signatures. We identified an eight-lncRNA signature (LINC00630, HDAC2-AS2, LINC01278, AL356599.1, AC114490.1, AL132639.3, FUT8.AS1, and TTC28.AS1), which separated the patients into two groups with significantly different overall survival rates. A nomogram based on the signature, BCR ABL1 status and white blood cell count at diagnosis was developed and showed good accuracy for predicting the 3-, 5- and 7-year survival probability of cALL patients. The C-index values of the nomogram in the training and internal validation set reached 0.8 (95% CI, 0.757 to 0.843) and 0.806 (95% CI, 0.728 to 0.884), respectively. The nomogram proposed in this study objectively and accurately predicted the prognosis of cALL. In vitro experiments suggested that LINC01278 promoted the proliferation of leukemic cells and inhibited leukemic cell apoptosis by targeting the inhibition of miR-500b-3p in cALL, and LINC01278 may be a biological target for the treatment of cALL in the future.

Expression and Clinical Significance of Long Non-Coding RNA RP4-669H2.1 in Glioblastoma

Neuroglioma is the most common malignant tumor in the central nervous system and still has a poor prognosis. Here, we investigated the prognostic value of long non-coding RNAs(lncRNAs) in glioblastoma. We first analyzed the lncRNA expression profiles of glioblastoma (GBM) in The Cancer Genome Atlas database and selected the most differential survival genes (lncRNA RP4-669H2.1) for further validation. We then performed qRT-PCR using samples of 88 glioblastoma patients treated in our department between January 2011 and December 2017 that were retrospectively selected to validate the prognostic value of RP4-669H2.1expression in glioblastoma. Using a Cox multivariate analysis, we explored the prognostic value of RP4-669H2.1 and analyzed whether it was an independent prognostic factor. This analysis confirmed that the RP4-669H2.1 expression was significantly associated with glioblastoma-associated mortality in this patient cohort (P =1.80E–05) in TCGA database. In fact, the overall survival (OS) of the RP4-669H2.1 high-expression group (78 cases) was lower than that of the low-expression group (49 cases) (P = 4.6E–06) in TCGA database. Moreover, the TNM stage of the RP4-669H2.1 high-expression group was higher than that of the RP4-669H2.1 low-expression group (P = 0.001). A multivariate analysis further showed that a higher TNM stage (OR = 2.167, 95% CI: 1.349–3.479) and a higher RP4-669H2.1 expression (OR = 2.933, 95% CI: 1.122–7.663) were independent risk factors for the OS of glioblastoma patients. Finally, we predicted the target genes of RP4-669H2.1 using a Multi Experiment Matrix and annotated their biological functions. We observed that the target genes of RP4-669H2.1 were mainly enriched in biological functions related to DNA-binding transcription factor activity. Among these, we selected SMAD6 because the expression of RP4-669H2.1 was positively correlated with that of SMAD6 in glioblastoma. Overall, we conclude that the upregulation of RP4-669H2.1 is an independent poor prognosis factor for glioblastoma and that it can regulate the DNA-binding activity of transcription factors.

The value of long noncoding RNAs for predicting the recurrence of endometriosis: A protocol for meta-analysis and bioinformatics analysis.

Background:As a gynecological disease, endometriosis (EM) seriously endangers the health of women at the age of childbearing and is closely related to long noncoding RNAs (lncRNAs). Current studies have discovered that there are differential expressions of many kinds of lncRNAs in EM. However, whether lncRNAs can be applied as a new marker for the prediction of the recurrence of EM is still controversial. In this study, meta-analysis and bioinformatics analysis were carried out to explore the value of lncRNAs as a predictor of the recurrence of EM and to analyze its biological role.Methods:PubMed, Embase, and Web of Science databases were searched through computer and the articles published from the self-built database to April 2021 were collected. According to the inclusion and exclusion criteria, the literature was screened, and the quality of the inclusion study was evaluated. Stata 16.0 software was used for meta-analysis. The co-expression genes related to lncRNAs were screened by online tool Co-LncRNA. Then David for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were conducted. A competitive endogenous RNA network that may exist in lncRNAs through Starbase was built.Results:The results of this meta-analysis would be submitted to peer-reviewed journals for publication.Conclusion:This meta-analysis could provide high-quality evidence support for lncRNAs, so as to predict the recurrence of EM. At the same time, we use bioinformatics technology to predict and analyze its biological effects, which provides a theoretical basis for further experimental verification.Ethics and dissemination:The private information from individuals will not be published. This systematic review also should not damage participants’ rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.OSF Registration Number:DOI 10.17605/OSF.IO/MF3QJ.

Novel Long Non-coding RNA and LASSO Prediction Model to Better Identify Pulmonary Tuberculosis: A Case-Control Study in China.

IntroductionThe insufficient understanding and misdiagnosis of clinically diagnosed pulmonary tuberculosis (PTB) without an aetiological evidence is a major problem in the diagnosis of tuberculosis (TB). This study aims to confirm the value of Long non-coding RNA (lncRNA) n344917 in the diagnosis of PTB and construct a rapid, accurate, and universal prediction model.MethodsA total of 536 patients were prospectively and consecutively recruited, including clinically diagnosed PTB, PTB with an aetiological evidence and non-TB disease controls, who were admitted to West China hospital from Dec 2014 to Dec 2017. The expression levels of lncRNA n344917 of all patients were analyzed using reverse transcriptase quantitative real-time PCR. Then, the laboratory findings, electronic health record (EHR) information and expression levels of n344917 were used to construct a prediction model through the Least Absolute Shrinkage and Selection Operator algorithm and multivariate logistic regression.ResultsThe factors of n344917, age, CT calcification, cough, TBIGRA, low-grade fever and weight loss were included in the prediction model. It had good discrimination (area under the curve = 0.88, cutoff = 0.657, sensitivity = 88.98%, specificity = 86.43%, positive predictive value = 85.61%, and negative predictive value = 89.63%), consistency and clinical availability. It also showed a good replicability in the validation cohort. Finally, it was encapsulated as an open-source and free web-based application for clinical use and is available online at https://ziruinptb.shinyapps.io/shiny/.ConclusionCombining the novel potential molecular biomarker n344917, laboratory and EHR variables, this web-based prediction model could serve as a user-friendly, accurate platform to improve the clinical diagnosis of PTB.

LncRNA XIST promotes liver cancer progression by acting as a molecular sponge of miR-200b-3p to regulate ZEB1/2 expression.

ObjectiveTo evaluate the predictive value of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) for survival, and determine the involvement of miRNA(miR)-200b-3p and zinc finger E-box-binding homeobox (ZEB) 1/2 in the pro-tumor effect of lncRNA XIST in liver cancer.MethodsWe evaluated lncRNA XIST expression in liver cancer tissues and cell lines by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and analyzed the correlation between its expression and overall survival of liver cancer patients by Kaplan–Meier analysis. Its effects on cell proliferation, migration, and invasion were analyzed by Cell-Counting Kit-8 and Transwell assays. The association between lncRNA XIST and miR-200b-3p, and the effects of lncRNA XIST on ZEB1/2 expression were explored using luciferase reporter assays, real-time PCR, and western blotting.ResultsThe lncRNA XIST was significantly upregulated in liver cancer, and increased lncRNA XIST expression was associated with a poor prognosis. The lncRNA XIST promoted liver cancer cell proliferation, migration, and invasion in vitro, and acted as a molecular sponge for miR-200b-3p, and also regulated the expression of ZEB1/2 via miR-200b-3p.ConclusionThe lncRNA XIST is an oncogenic lncRNA that promotes liver cancer metastasis, and its pro-metastatic phenotype can be partially attributed to the lncRNA XIST/miR-200b-3p/ZEB1/2 signaling axis.

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.

An Autophagy-Related Long Noncoding RNA Signature Contributes to Poor Prognosis in Colorectal Cancer.

Purpose Colorectal cancer is one of the most common malignant primary tumors, prone to metastasis, and associated with a poor prognosis. As autophagy is closely related to the development and treatment of colorectal cancer, we investigated the potential prognostic value of long noncoding RNA (lncRNA) associated with autophagy in colorectal cancer. Methods In this study, we acquired information on the expression of lncRNAs in colorectal cancer from the Cancer Genome Atlas (TCGA) database and found that 860 lncRNAs were associated with autophagy-related genes. Subsequently, univariate Cox regression analysis was used to investigate 32 autophagy-related lncRNAs linked to colon cancer prognosis. Subsequently, eight of the 32 autophagy-related lncRNAs (i.e., long intergenic nonprotein coding RNA 1503 [LINC01503], ZEB1 antisense RNA 1 [ZEB1-AS1], AC087481.3, AC008760.1, AC073896.3, AL138756.1, AL022323.1, and TNFRSF10A-AS1) were selected through multivariate Cox regression analysis. Based on these autophagy-related lncRNAs, a risk signature was constructed, and the patients were divided into high- and low-risk groups. Results The high-risk group's overall survival time was significantly shorter than that of the low-risk group (p < 0.0001). Receiver operating characteristic curve analysis was performed to further confirm the validity of the model (area under the curve: 0.689). Moreover, multivariate regression suggested that the risk score was a significant prognostic risk factor in colorectal cancer. Gene set enrichment analysis showed that these gene sets are significantly enriched in cancer-related pathways, such as Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling. Conclusion The risk signature of eight autophagy-related lncRNAs has prognostic potential for colorectal cancer. These autophagy-related lncRNAs may play a vital role in the biology of colorectal cancer.

The prognostic value of long noncoding RNA activated by TGF-β in digestive system cancers: A meta-analysis.

Background:To systematically evaluate whether the expression level of long non-coding RNA activated by transforming growth factor-β (lncRNA-ATB) is correlated with the prognosis of digestive system cancer (DSC) patients.Methods:PubMed, Embase, Cochrane Library, Web of Science, Springerlink, Nature, and Karger databases were searched up to April 20, 2019 by 2 experienced researchers independently. The quality of studies was assessed with the Newcastle-Ottawa scale. The Review Manager 5.2 and STATA 12.0 software were used for this meta-analysis.Result:Eleven studies with 1227 DSC patients were included in the meta-analysis. Except for pancreatic cancer, high expression of lncRNA-ATB was associated with lymph node metastasis (risk ratio (RR) = 1.26, 95% confidence interval (CI): 1.12–1.42, P < .001), advanced clinical staging (RR = 1.44, 95%CI: 1.23–1.69, P < .001), reduced overall survival rate (OS) (hazard ratio (HR) = 2.33, 95%CI: 1.22–4.50, P = .01), and recurrence-free survival (RFS) (HR = 2.61, 95%CI: 1.46–4.65, P = .001) compared with low lncRNA-ATB expression in DSCs.Conclusions:High expression of lncRNA-ATB was significantly correlated with poor prognosis for most DSCs. The expression level of lncRNA-ATB could be a promising prognostic biomarker for DSC patients.

The correlation of serum long non-coding RNA ANRIL with risk factors, functional outcome, and prognosis in atrial fibrillation patients with ischemic stroke.

BackgroundThis study aimed to evaluate the predictive value of long non‐coding RNA (lncRNA) antisense non‐coding RNA in the INK4 locus (ANRIL) for atrial fibrillation (AF) patients with ischemic stroke and investigate its correlation with risk factors, functional outcome, and prognosis.MethodsA total of 386 consecutive AF patients were recruited. AF patients were followed up for 24‐48 months by outpatient follow‐up, telephone follow‐up, and medical record. The time of ischemic stroke in patients with AF was recorded, and follow‐up was continued for 6 months. LncRNA ANRIL expression from serum was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR).ResultsCompared with the AF with ischemic stroke group (14.3 ± 2.3), patients in the AF without ischemic stroke group (11.9 ± 1.8) had significantly lower serum lncRNA ANRIL levels (P < .05). The sensitivity and specificity of lncRNA ANRIL for identifying AF with ischemic stroke were 76.6% and 81.4%, respectively. Spearman correlation analysis results shown that lncRNA ANRIL was significantly correlated with the NIHSS score (r Spearman = .490, P < .001) and the mRS score (r Spearman = .466, P < .001). Compared with the lncRNA ANRIL high‐expression group, the recurrence‐free survival (RFS) of the lncRNA ANRIL low‐expression group was significantly higher (χ2 = 11.009, log‐rank P < .001). Cox proportional regression model analysis indicated that the serum lncRNA ANRIL level (P = .004), NIHSS score (P = .001), infarct volume (P = .035), and smoking (P < .001) were the risk factors for AF with ischemic stroke.ConclusionSerum lncRNA ANRIL exerts a good predictive value for AF with ischemic stroke, and its increased expression is correlated with worse RFS for patients.

Long Noncoding RNA Maternally Expressed Gene 3 Is Downregulated, and Its Insufficiency Correlates With Poor-Risk Stratification, Worse Treatment Response, as Well as Unfavorable Survival Data in Patients With Acute Myeloid Leukemia.

Objective:Our study aimed to investigate the correlation of long noncoding RNA maternally expressed gene 3 expression with clinical features, treatment response, and survival profiles in patients with acute myeloid leukemia.Methods:Bone marrow samples of 122 de novo patients with acute myeloid leukemia (prior to treatment) and 30 healthy donors (after enrollment) were collected, and long noncoding RNA maternally expressed gene 3 expression was detected by reverse transcription quantitative polymerase chain reaction. According to median value of long noncoding RNA maternally expressed gene 3 expression in patients with acute myeloid leukemia, they were divided into long noncoding RNA maternally expressed gene 3 high expression and low expression patients (which were further categorized as low---, low--, and low- expression patients).Results:Long noncoding RNA maternally expressed gene 3 expression was decreased in patients with acute myeloid leukemia compared to healthy donors. Besides, receiver operating characteristic curve displayed that long noncoding RNA maternally expressed gene 3 distinguished patients with acute myeloid leukemia from healthy donors. In patients with acute myeloid leukemia, long noncoding RNA maternally expressed gene 3 low expression was associated with poor-risk stratification but was not correlated with age, gender, French-American-Britain classification, or white blood cell level. For prognosis, complete remission rate was lowest in long noncoding RNA maternally expressed gene 3 low--- expression patients, followed by long noncoding RNA maternally expressed gene 3 low-- expression patients, long noncoding RNA maternally expressed gene 3 low- expression patients, and was highest in long noncoding RNA maternally expressed gene 3 high expression patients; Kaplan-Meier curves displayed that lower long noncoding RNA maternally expressed gene 3 expression was associated with reduced event-free survival and overall survival; Cox regression analysis showed that lower long noncoding RNA maternally expressed gene 3 expression independently predicted decreased event-free survival and worse overall survival in patients with acute myeloid leukemia.Conclusion:Long noncoding RNA maternally expressed gene 3 may function as a novel marker for effective surveillance and management of acute myeloid leukemia.

Diagnostic Value of lncRNA ROR in Differentiating Ovarian Cancer Patients.

The current study aims to investigate the prognostic value of long non-coding RNA (lncRNA) ROR in ovarian cancer patients. Sixty cases of ovarian cancer patients were collected from January 2017 to December 2017. The expression of lncRNA ROR in the plasma and tissues of ovarian cancer was detected by RT-qPCR. The relationship between the expression of lncRNA ROR and the clinicopathological characteristics was analyzed. The expression of lncRNA ROR in the plasma of ovarian cancer patients was significantly higher than that in healthy controls. Compared with that in the adjacent non-cancerous tissues, the level of lncRNA ROR was significantly enhanced in the ovarian cancer tissues. Further study showed that the expression of lncRNA ROR was closely related to FIGO stage, tumor grade, and lymph node metastasis. Pearson's correlation assay indicated that lncRNA ROR positively correlated with CA125 in ovarian cancer patients. Moreover, the combined detection of plasma lncRNA ROR and CA125 had the highest value in the diagnosis of ovarian cancer compared to that of lncRNA ROR or CA125 alone. The enhanced level of plasma lncRNA ROR could be used as a potential biomarker for the diagnosis of ovarian cancer.

Clinical diagnostic value of long non-coding RNAs in Colorectal Cancer: A systematic review and meta-analysis.

Background: Histopathological diagnosis remains the gold standard for the diagnosis of cancer, including colorectal cancer, but it is infeasible when tumor tissue is not available. With the recognition of long non-coding RNAs (lncRNAs), the expression of lncRNAs in serum or tissue samples has been reported as a diagnosis method for some cancers, however, the diagnostic value of lncRNAs for colorectal cancer remains unclear.Methods: A systematic review and meta-analysis were conducted. Eligible studies were identified through a comprehensive literature search in PubMed, PubMed Central, Web of Science, Embase, and Cochrane Library (up to May 05, 2020) according to the selection criteria. Meta-DiSc, Review Manager and STATA were used to analyze the association between lncRNAs expression and the diagnosis of colorectal cancer.Results: Fifteen studies that analyzed the expression of 15 lncRNAs in 1434 CRC patients were included. The summary area under the curve (AUC) of lncRNA for the diagnosis efficacy between patients with and without CRC was estimated to be 0.8629, corresponding to a weighted sensitivity of 0.75 (95% CI: 0.72 - 0.77), specificity of 0.80 (95%CI: 0.78 - 0.82). Subgroup analysis illustrated that the AUC of blood-based detection of lncRNA showed 0.8820, pooled DOR: 18.57, while tissue-based analysis showed 0.8203, pooled DOR: 10.47. Blood-based tests were then divided into two categories, plasma-based and serum-based lncRNA testing. Results revealed that the AUC of serum-based detection was 0.9077, pooled DOR: 26.64, and plasma-based detection was 0.5000, pooled DOR: 11.80.Conclusions: This meta-analysis indicates that the aberrantly expressed lncRNAs might serve as potential diagnostic biomarkers for CRC patients and blood-based lncRNA analysis is of higher diagnostic accuracy than tissue-based testing. Moreover, serum-based lncRNA testing achieved higher diagnostic efficacy than plasma-based analysis.

Expression and clinical value of lncRNA MALAT1 and lncRNA ANRIL in glaucoma patients.

Expression and clinical value of long non-coding RNA (lncRNA) MALAT1 and lncRNA ANRIL in glaucoma patients were investigated. Altogether 86 glaucoma patients who were diagnosed (study group) and 86 people who underwent physical examinations and were confirmed to be healthy (control group) in the Hospital of Chengdu University of Traditional Chinese Medicine from January 2016 to June 2018 were enrolled. Expression of the serum lncRNA MALAT1, lncRNA ANRIL, pigment epithelium-derived factor (PEDF), homocysteine (Hcy), and inflammatory cytokines [interleukin-12 (IL-12), interleukin-4 (IL-4) and interferon-γ (IFN-γ)] was detected. The clinical significance of lncRNA MALAT1 and lncRNA ANRIL was analyzed. Compared with those in the control group, patients in the study group had significantly lower expression of serum lncRNA MALAT1 and lncRNA ANRIL (P<0.05), significantly lower expression of serum PEDF and IL-12 (P<0.05), and significantly higher expression of serum Hcy and IL-4 (P<0.05), without significant difference in the expression of serum IFN-γ between the two groups (P>0.05). Serum lncRNA MALAT1 and lncRNA ANRIL were positively correlated with PEDF and IL-12 (P<0.05), but negatively correlated with Hcy and IL-4 (P<0.05). The diagnostic value of the combined detection of lncRNA MALAT1 and lncRNA ANRIL was higher than that of lncRNA MALAT1 alone and lncRNA ANRIL alone. The expression of lncRNA MALAT1 and lncRNA ANRIL was significantly related to the pathological staging of the patients (P<0.05), not the sex, age, body mass index (BMI), types, and presence or absence of myopia (P>0.05). lncRNA MALAT1 and lncRNA ANRIL are poorly expressed in the serum of glaucoma patients and related to the patients' conditions. Their combined detection has high diagnostic value for the disease. Therefore, they may be used as new molecular targets for the diagnosis and severity evaluation of glaucoma patients.

Inhibition of LncRNA FOXD3-AS1 suppresses the aggressive biological behaviors of thyroid cancer via elevating miR-296-5p and inactivating TGF-β1/Smads signaling pathway

BackgroundThyroid cancer is the most common malignant tumor with relatively high incidence and mortality in endocrine system. Research about thyroid cancer-related targets is the basis for the diagnosis of thyroid cancer and the development of new drugs. However, the predictive value of long non-coding RNA (lncRNA) for the diagnosis and prognosis of thyroid cancer is still in the preliminary stage of exploration. Thus, we for the first time investigated the effects and associated regulatory mechanism of lncRNA Forkhead box D3 antisense RNA 1 (FOXD3-AS1) in thyroid cancer in vitro and in vivo. MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of lncRNA FOXD3-AS1 and miR-296-5p. Cell proliferation was detected through colony formation assay. Cell cycle was analyzed through flow cytometry. Cell mobility was valued through transwell invasion assay and wound healing assay. Western blotting was used to examine the expression of proteins related to cell proliferation and cell migration and TGF-β1/Smads signaling pathway. Luciferase reporter assay was used to verify the targeting relationship between FOXD3-AS1 and miR-296-5p. Tumor xenograft model was established and immunohistochemistry (IHC) was used to examine the expression of Ki67 and VEGF. ResultsWe found that the expression of lncRNA FOXD3-AS1was upregulated and it had negative correlation with the level of miR-296-5p in thyroid cancer tissues and cells. LncRNA FOXD3-AS1 knockdown effectively suppressed cell proliferation and cell invasion in vitro. Further study revealed that miR-296-5p was a target of lncRNA FOXD3-AS1 and FOXD3-AS1 exerted anti-tumor effect through up-regulating miR-296-5p. Moreover, we found that FOXD3-AS1 knockdown suppressed the aggressive biological behaviors of thyroid cancer through inactivating the TGF-β1/Smads signaling pathway. Subsequently, the in vivo experiments further verified that the FOXD3-AS1/miR-296-5p axis exerted obvious anti-tumor effect through inhibiting tumor growth and metastasis and the TGF-β1/Smads signaling pathway was also inactivated in vivo by the inhibition of FOXD3-AS1. ConclusionInhibition of LncRNA FOXD3-AS1 suppresses the aggressive biological behaviors of thyroid cancer via elevating miR-296-5p and inactivating TGF-β1/Smads signaling pathway.

Prognostic significance of long non-coding RNAs in clear cell renal cell carcinoma: A meta-analysis.

Background:Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer in adults, and patients with advanced ccRCC have a 5-year survival rate of <30%. The poor prognosis of ccRCC is closely related to its lacking of potential therapeutic and prognostic biomarkers. This meta-analysis aimed to elucidate the precise prognostic value of long non-coding RNAs (lncRNAs) in patients with ccRCC.Methods:A literature search was performed in related databases up to January 31, 2019. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to explore the relationship between special lncRNAs expression and survival in patients with ccRCC.Results:After literature researching, a total of 16 studies, including 13 lncRNAs were identified. The data from studies that investigated the association between lncRNA expression and survival outcomes in patients with ccRCC were extracted. Results revealed that lncRNAs expression was significantly associated with poor overall survival (OS) outcome in patients with ccRCC (HR = 1.71, 95%CI = 1.40–2.01 in up-regulated subgroup; HR = 0.53, 95% CI = 0.25–0.80 in down-regulated subgroup). The overexpression of PVT1 was significantly associated with poor OS in ccRCC (HR = 1.51, 95% CI = 1.02–2.00). Meanwhile, up-regulation of LUCAT1 was significantly related to worse OS in ccRCC patients (HR = 1.51, 95% CI = 1.01–2.00).Conclusions:These results suggest that lncRNAs could be used to predict unfavorable prognosis and function as potential prognostic biomarkers in ccRCC.

Prognostic Value of Long Noncoding RNAs in Patients with Gastrointestinal Cancer: A Systematic Review and Meta-Analysis.

Gastrointestinal cancers (GICs) are a huge threat to human health, which mainly include esophageal, gastric, and colorectal cancers. The purpose of this study was to clarify the prognostic value of long noncoding RNAs (lncRNAs) in GICs. A total of 111 articles were included, and 13103 patients (3123 with esophageal cancer, 4972 with gastric cancer, and 5008 with colorectal cancer) were enrolled in this study. The pooled hazard ratio (HR) values and corresponding 95% confidence interval (95% CI) of overall survival (OS) related to different lncRNA expressions in esophageal, gastric, colorectal, and gastrointestinal cancer patients were 1.92 (1.70–2.16), 1.96 (1.77–2.16), 2.10 (1.87–2.36), and 2.00 (1.87–2.13), respectively. We have identified 74 lncRNAs which were associated closely with poor prognosis of GIC patients, including 58 significantly upregulated lncRNA expression and 16 significantly downregulated lncRNA expression. In addition, 47 of the included studies revealed relative mechanisms and 12 of them investigated the correlation between lncRNAs and microRNAs. Taken together, this meta-analysis supports that specific lncRNAs are significantly related to the prognosis of GIC patients and may serve as novel markers for predicting the prognosis of GIC patients. Furthermore, lncRNAs may have a promising contribution to lncRNA-based targeted therapy and clinical decision-making in the future.

The Prognostic Value of lncRNAs Expression and Clinicopathological Feature in Gastric Cancer: A Field Synopsis of Observational Studies

Background: Data on prognostic value of long non-coding RNAs (lncRNAs) to sporadic gastric cancer have been published at a growing pace. However, there has been no comprehensive quantitative overview has been available. We aim to investigate the association between the expression of long non-coding RNAs (lncRNAs), clinicopathological factors and prognosis of gastric cancer. Methods: We explored correlation of lncRNA with clinicopathological features and prognosis. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), disease-free survival (DFS)/progression-free survival (PFS)/Disease Specific Survival (DSS)/recurrence-free survival (RFS) were calculated to estimate the association strength. Results: Literature search identified 80 eligible studies comprising 2205 cases which investigated senven gastric cancer associated clinicopathological factors. Overall, a significant association was observed between high lncRNAs level and poor OS in patients with gastric cancer (HR = 1.46, 95% CI: 1.31-1.63, P<0.001). We conduct stratified analysis based on statistical approach showing that high expression of lncRNAs in both log rank (HR=1.64, 95%CI: 1.32-2.03, P<0.001) and multivariate analysis (HR=1.37, 95%CI: 1.21-1.55, P<0.001) were significant associated with poor OS, and the pooled HR of association between elevated lncRNAs expression level and DFS/PFS/DSS/RFS in gastric cancer patients was 1.60 (95% CI: 1.29-1.98, P<0.001). For the OS, the results showed that the lncRNA expression level was signifcantly associated the clinicopathological parameters including TNM stage (P<0.001), tumor size (P<0.001), pathological differention (P=0.02), lymph nodes metastasis (P<0.001), distance metastasis (P<0.001) and invasion depth (P<0.001), and there was significant association in TNM stage (P<0.001), lymph nodes metastasis (P<0.001), distance metastasis (P<0.001), and invasion depth (P=0.02) for DFS. Conclusion: High expression of lncRNA could predict poor prognosis in gastric cancer, and abnormal expression of lncRNAs supported the clinical value regarding the clinicopathological factors. Funding: This study was funded by National Natural Science Foundation of China (81701536, 81373097). Declaration of Interest: The authors declare no conflict of interest.

A novel lncRNA-focus expression signature for survival prediction in endometrial carcinoma

BackgroundEndometrial cancer (UCEC) is a complex malignant tumor characterized by both genetic level and clinical trial. Patients with UCEC exhibit the similar clinical features, however, they have distinct outcomes due to molecular heterogeneity. The aim of this study was to access the prognostic value of long non-coding RNAs (lncRNAs) in UCEC patients and to identify potential lncRNA signature for predicting patients’ survival and improving patient-tailored treatment.MethodsWe performed a comprehensive genome-wide analysis of lncRNA expression profiles and clinical data in a large cohort of 301 UCEC patients. UCEC patients were randomly divided into the discovery cohort (n = 150) and validation cohort (n = 151). A novel lncRNA-focus expression signature was identified in the discovery cohort, and independently accessed in the validation cohort. Additionally, the lncRNA signature was evaluated by multivariable Cox regression and stratification analysis as well as functional enrichment analysis.ResultsWe detected a novel lncRNA-focus expression signature (LFES) consisting of 11 lncRNAs that were associated with survival based on risk scoring strategy in UCEC. The risk score based on the LFES was able to separate patients of discovery cohort into high-risk and low-risk groups with significantly different overall survival and progression-free survival, and has been successfully confirmed in the validation cohort. Furthermore, the LFES is an independent prognostic predictor of survival and demonstrates superior prognostic performance compared with the clinical covariates for predicting 5-year survival (AUC = 0.887). Functional analysis has linked the expression of prognostic lncRNAs to well-known tumor suppressor or ontogenetic pathways in endometrial carcinogenesis.ConclusionsOur study revealed a novel 11-lncRNA signature to predict survival of UCEC patient. This lncRNA signature may be a valuable and alternative marker for risk evaluation to aid patient-tailored treatment and improve the outcome of patients with UCEC.

Plasma Long Non-Coding RNA (lncRNA) GAS5 is a New Biomarker for Coronary Artery Disease.

Our study aimed to investigate the diagnostic value of long non-coding RNA (lncRNA) GAS5 for coronary artery disease (CAD) and to explore the mechanism of the role of GAS5 in CAD.A total of 30 patients with CAD were selected from January 2015 to January 2017 in The First Hospital of Tianmen. In addition, 30 healthy individuals were selected as a control group, and patients with various other types of cardiovascular diseases were also selected. Expression of GAS5 in plasma of all participants was detected by quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was performed to investigate the diagnostic value of GAS5 for CAD. Levels of mammalian target of rapamycin (mTOR) and phospho-mTOR (p-mTOR) in human primary coronary artery endothelial cells (HCAECs) were detected by western blotting.Compared with normal healthy people, expression level of lncRNA Novlnc6 was significantly reduced in patients with CAD and diabetes mellitus, but not in patients with other types of cardiovascular diseases, such as hypertension, abnormal aortic aneurysm, viral myocarditis. In addition, the expression level of GAS5 was significantly lower in patients with CAD compared to patients with diabetes mellitus. ROC curve analysis showed that GAS5 may serve as a promising biomarker for CAD. GAS5 knockdown and overexpression showed no significant effect on the level of mTOR) in HCAECs. However, GAS5 knockdown significantly increased the level of phospho-mTOR (p-mTOR), and GAS5 overexpression significantly decreased the level of p-mTOR. Treatment with mTOR inhibitor and activator showed no significant effect on expression of GAS5 in HCAECs.GAS5 plays a role as upstream regulator of the mTOR pathway to participate in the development of CAD. GAS5 was specifically downregulated in patients with CAD, and it may serve as a promising biomarker for CAD.