• LncRNA
• Osteoclasts
• Osteoporosis
• Treatment

• RNA, Long Noncoding/genetics
• Humans
• Osteoporosis/genetics
• Osteoporosis/pathology
• Osteoclasts/pathology
• Osteoclasts/metabolism
• Cell Differentiation/genetics
• Animals
• Osteogenesis/genetics
• Osteogenesis/physiology

• EGFR
• HER2
• HER3
• HER3-targeted therapy
• SIBP-03
• neuregulin 1

• Humans
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Cell Line, Tumor
• Phosphatidylinositol 3-Kinases/metabolism
• Receptor, ErbB-2/metabolism
• Receptor, ErbB-3/antagonists & inhibitors
• Receptor, ErbB-3/metabolism
• Signal Transduction
• Trastuzumab/pharmacology
• Trastuzumab/therapeutic use
• Antibodies, Monoclonal/immunology
• Antibodies, Monoclonal/therapeutic use
• Neoplasms/therapy

• (S)-10-hydroxycamptothecin
• EMT
• HIPPO
• Osteosarcoma
• large tumor suppressor.
• metastasis

• Humans
• Osteosarcoma/drug therapy
• Osteosarcoma/pathology
• Osteosarcoma/metabolism
• Camptothecin/pharmacology
• Camptothecin/analogs & derivatives
• Hippo Signaling Pathway/drug effects
• Cell Proliferation/drug effects
• Epithelial-Mesenchymal Transition/drug effects
• Signal Transduction/drug effects
• Protein Serine-Threonine Kinases/metabolism
• Bone Neoplasms/drug therapy
• Bone Neoplasms/pathology
• Bone Neoplasms/metabolism
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Dose-Response Relationship, Drug

• (2021LK047). Shanghai University of Traditional Chinese Medicine
• (81973877 and 82174408) National Natural Science Foundation of China (NSFC)

• bone metastasis
• hippo-YAP pathway
• liver hepatocellular carcinoma
• prognosis
• topoisomerase 2A

• Humans
• Carcinoma, Hepatocellular/genetics
• Liver Neoplasms/genetics
• Bone Neoplasms/genetics
• Biological Assay
• Prognosis

• Breast cancer
• Non-coding RNAs
• Organs
• Pathways
• Subtypes
• Tumor cells
• Tumor microenvironment

• Humans
• Female
• Breast Neoplasms/pathology
• Tumor Microenvironment/genetics
• Melanoma
• Tropism
• Neoplasm Metastasis
• Melanoma, Cutaneous Malignant

• hepatocytes
• long noncoding RNA
• nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis
• signaling pathway

• Humans
• Non-alcoholic Fatty Liver Disease/genetics
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Liver/metabolism

• Biomarker
• Cancer
• LINC-PINT
• LncRNA
• Tumor suppressor gene

Although recent evidence has shown that hepatocyte senescence plays a crucial role in the pathogenesis and development of non‐alcoholic fatty liver disease (NAFLD), the mechanism is still not clear. The purpose of this study was to investigate the signal transduction pathways involved in the senescence of hepatocyte, in order to provide a potential strategy for blocking the process of NAFLD. The results confirmed that hepatocyte senescence occurred in HFD‐fed Golden hamsters and PA‐treated LO2 cells as manifested by increased levels of senescence marker SA‐β‐gal, p16 and p21, heterochromatin marker H3K9me3, DNA damage marker γ‐H2AX and decreased activity of telomerase. Further studies demonstrated that iron overload could promote the senescence of hepatocyte, whereas the overexpression of Yes‐associated protein (YAP) could blunt iron overload and alleviate the senescence of hepatocyte. Of importance, depression of lncRNA MAYA (MAYA) reduced iron overload and cellular senescence via promotion of YAP in PA‐treated hepatocytes. These effects were further supported by in vivo experiments. In conclusion, these data suggested that inhibition of MAYA could up‐regulate YAP, which might repress hepatocyte senescence through modulating iron overload. In addition, these findings provided a promising option for heading off the development of NAFLD by abrogating hepatocyte senescence.

• MAYA
• Yes-associated protein
• cellular senescence
• iron overload
• non-alcoholic fatty liver disease

• epithelial-to-mesenchymal transition
• growth factors
• metastasis
• mutation
• tumor microenvironments
• wound healing

• Breast cancer
• Metastasis
• Metastatic suppressors
• Runx2
• ncRNAs

Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined.

qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2.

LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8⁺ T cell population in LA-4/SLN-205-derived tumors through targeting TGF-β. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83–123 nucleotide [nt]) can directly bind to the enhancer of zeste homolog 2 (EZH2) (612–727 amino acid [aa]) to promote H3K27me3 at the ELL protein-associated factor 2 (EAF2) promoter. EAF2 directly binds and stabilizes von Hippel–Lindau protein (pVHL), so downregulated EAF2 augments hypoxia-inducible factor 1 α (HIF1α) expression by regulating pVHL in NSCLC cells. Moreover, we also found that LINC00301 could function as a competing endogenous RNA (ceRNA) against miR-1276 to expedite HIF1α expression in the cytoplasm of NSCLC cells.

In summary, our present research revealed the oncogenic roles of LINC00301 in clinical specimens as well as cellular and animal experiments, illustrating the potential roles and mechanisms of the FOXC1/LINC00301/EZH2/EAF2/pVHL/HIF1α and FOXC1/LINC00301/miR-1276/HIF1α pathways, which provides novel insights and potential theraputic targets to NSCLC.

• ELL protein-associated factor 2 (EAF2)
• Enhancer of zeste homolog 2 (EZH2)
• Hypoxia-inducible factor 1 α (HIF1α)
• LINC00301
• Non-small cell lung cancer (NSCLC)
• Regulatory T cells (Treg)
• Tumorigenesis
• miR-1276

• Computational biology
• Drug design
• Glioma
• Long noncoding
• RNA
• Risk factors

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/therapeutic use
• Brain Neoplasms/drug therapy
• Brain Neoplasms/genetics
• Brain Neoplasms/mortality
• Brain Neoplasms/pathology
• Female
• Glioma/drug therapy
• Glioma/genetics
• Glioma/mortality
• Glioma/pathology
• Humans
• Male
• MicroRNAs/metabolism
• Middle Aged
• Prognosis
• RNA, Long Noncoding/metabolism
• RNA, Messenger/metabolism
• Risk
• Young Adult

• brain
• lncRNA
• lung adenocarcinoma
• metastases
• microRNA

The receptor tyrosine kinase ROR1 is absent in most normal adult tissues, but overexpressed in several malignancies. In this study, we explored clinical and functional inhibitory aspects of ROR1 in diffuse large B-cell lymphoma (DLBCL). ROR1 expression in tumor cells was more often observed in primary refractory DLBCL, Richter’s syndrome and transformed follicular lymphoma than in relapsed and non-relapsed DLBCL patients (p < 0.001). A survival effect of ROR1 expression was preliminarily observed in relapsed/refractory patients independent of gender and stage but not of age, cell of origin and international prognostic index. A second generation small molecule ROR1 inhibitor (KAN0441571C) induced apoptosis of ROR1+ DLBCL cell lines, similar to venetoclax (BCL-2 inhibitor) but superior to ibrutinib (BTK inhibitor). The combination of KAN0441571C and venetoclax at EC₅₀ concentrations induced almost complete killing of DLBCL cell lines. Apoptosis was accompanied by the downregulation of BCL-2 and MCL-1 and confirmed by the cleavage of PARP and caspases 3, 8, 9. PI3Kδ/AKT/mTOR (non-canonical Wnt pathway) as well as β-catenin and CK1δ (canonical pathway) were inactivated. In zebra fishes transplanted with a ROR1+ DLBCL cell line, KAN0441571C induced a significant tumor reduction. New drugs with mechanisms of action other than those available for DLBCL are warranted. ROR1 inhibitors might represent a novel promising approach.

• DLBCL
• ROR1
• small molecules

A growing number of studies recognize that long non‐coding RNAs (lncRNAs) are essential to mediate multiple tumorigenic processes, including hepatic tumorigenesis. However, the pathological mechanism of lncRNA‐regulated liver cancer cell growth remains poorly understood. In this study, we identified a novel function lncRNA, named polo‐like kinase 4 associated lncRNA (lncRNA PLK4, GenBank Accession No. RP11‐50D9.3), whose expression was dramatically down‐regulated in hepatocellular carcinoma (HCC) tissues and cells. Interestingly, talazoparib, a novel and highly potent poly‐ADP‐ribose polymerase 1/2 (PARP1/2) inhibitor, could increase lncRNA PLK4 expression in HepG2 cells. Importantly, we showed that talazoparib‐induced lncRNA PLK4 could function as a tumour suppressor gene by Yes‐associated protein (YAP) inactivation and induction of cellular senescence to inhibit liver cancer cell viability and growth. In summary, our findings reveal the molecular mechanism of talazoparib‐induced anti‐tumor effect, and suggest a potential clinical use of talazoparib‐targeted lncRNA PLK4/YAP‐dependent cellular senescence for the treatment of HCC.

• Yes-associated protein
• cellular senescence
• hepatocellular carcinoma
• polo-like kinase 4 associated lncRNA
• talazoparib

Long noncoding RNAs (lncRNAs) have been identified to participate in tumorigenesis. However, the underlying mechanisms of differentially expressed lncRNAs engaged in diseases remain indistinct and need further exploration.

Raw data files downloaded from TCGA and GEO dataset were used to analyze the differentially expressed lncRNAs and LINC00565 was picked out as the potential oncogene. qRT-PCR was used to analyze the LINC00565 level in ovarian tissues and cell lines. Subsequently, the selected ovarian tumor cells were then transfected with LINC00565 siRNA by Lipofectamine 2000 and the cell cycle was detected by flow cytometry. Effect of LINC00565 on tumor growth and cell cycle was verified by tumor formation assay in nude mice. The mechanism of LINC00565 involving in cell cycle regulation was further explored by Western blot.

In this research, we discovered that LINC00565, a novel lncRNA, was highly expressed in ovarian cancer (OC). LINC00565 expression level was negatively associated with outcomes of OC patients. Further analysis showed that LINC00565 expression was closely correlated to tumor size, FIGO stage, but not related to other clinical features. In vitro experiments indicated that knockdown of LINC00565 significantly inhibited proliferative, invasive and migratory abilities of ovarian cancer cells. Besides, knockdown of LINC00565 can induce cell cycle arrest in G0/G1 phase. In addition, in vivo assay showed that low expression of LINC00565 inhibited the growth of OC. Further study found that LINC00565 knockdown markedly downregulated the protein expressions of CyclinD1, CyclinE1 and CDK4, but upregulated the expression of P16 and P21. Subsequently, we confirmed that LINC00565 promoted the progression of OC via upregulating GAS6, which has been confirmed to promote tumor progression.

In summary, our study firstly reported that the LINC00565 functioned as an oncogene to promote the progression of OC by interacting with GAS6.

• GAS6
• LINC00565
• OC
• cell cycle
• ovarian cancer

Long non-coding RNAs (lncRNAs) play important roles in many diseases, including hepatocellular carcinoma (HCC). Autophagy is a metabolic pathway that facilitates cancer cell survival in response to stress. The relationship between autophagy and the lncRNA-activated by transforming growth factor beta (lncRNA-ATB) in HCC remains unknown.

To explore the influence of lncRNA-ATB in regulating autophagy in HCC cells and the underlying mechanism.

In the present study, we evaluated lncRNA-ATB expression in tumor and adjacent non-tumor tissues from 72 HCC cases by real-time PCR. We evaluated the role of lncRNA-ATB in the proliferation and clonogenicity of HCC cells in vitro. The effect of lncRNA-ATB on autophagy was determined using a LC3-GFP reporter and transmission electron microscopy. Furthermore, the mechanism by which lncRNA-ATB regulates autophagy was explored by immunofluorescence staining, RNA immunoprecipitation (RIP), and Western blot.

The expression of lncRNA-ATB was higher in HCC tissues than in normal liver tissues, and lncRNA-ATB expression was positively correlated with tumor size, TNM stage, and poorer survival of patients with HCC. Moreover, ectopic overexpression of lncRNA-ATB promoted cell proliferation and clonogenicnity of HCC cells in vitro. LncRNA-ATB promoted autophagy by activating Yes-associated protein (YAP). Moreover, lncRNA-ATB interacted with autophagy-related protein 5 (ATG5) mRNA and increased ATG5 expression.

LncRNA-ATB regulates autophagy by activating YAP and increasing ATG5 expression. Our data demonstrate a novel function for lncRNA-ATB in autophagy and suggest that lncRNA-ATB plays an important role in HCC.

• LncRNA-ATB
• Autophagy
• Yes-associated protein
• Autophagy-related protein 5
• Hepatocellular carcinoma

• Adaptor Proteins, Signal Transducing/genetics
• Autophagy/genetics
• Autophagy-Related Protein 5/genetics
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Cell Line, Tumor
• Cell Survival/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Liver/pathology
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Male
• Middle Aged
• RNA, Long Noncoding/metabolism
• Transcription Factors/genetics
• YAP-Signaling Proteins

Our previous genome-wide association study using the MA.27 aromatase inhibitors adjuvant trial identified SNPs in the long noncoding RNA MIR2052HG associated with breast cancer-free interval. MIR2052HG maintained ERα both by promoting AKT/FOXO3-mediated ESR1 transcription and by limiting ubiquitin-mediated ERα degradation. Our goal was to further elucidate MIR2052HG’s mechanism of action.

RNA-binding protein immunoprecipitation assays were performed to demonstrate that the transcription factor, early growth response protein 1 (EGR1), worked together with MIR2052HG to regulate that lemur tyrosine kinase-3 (LMTK3) transcription in MCF7/AC1 and CAMA-1 cells. The location of EGR1 on the LMTK3 gene locus was mapped using chromatin immunoprecipitation assays. The co-localization of MIR2052HG RNA and the LMTK3 gene locus was determined using RNA-DNA dual fluorescent in situ hybridization. Single-nucleotide polymorphisms (SNP) effects were evaluated using a panel of human lymphoblastoid cell lines.

MIR2052HG depletion in breast cancer cells results in a decrease in LMTK3 expression and cell growth. Mechanistically, MIR2052HG interacts with EGR1 and facilitates its recruitment to the LMTK3 promoter. LMTK3 sustains ERα levels by reducing protein kinase C (PKC) activity, resulting in increased ESR1 transcription mediated through AKT/FOXO3 and reduced ERα degradation mediated by the PKC/MEK/ERK/RSK1 pathway. MIR2052HG regulated LMTK3 in a SNP- and aromatase inhibitor-dependent fashion: the variant SNP increased EGR1 binding to LMTK3 promoter in response to androstenedione, relative to wild-type genotype, a pattern that can be reversed by aromatase inhibitor treatment. Finally, LMTK3 overexpression abolished the effect of MIR2052HG on PKC activity and ERα levels.

Our findings support a model in which the MIR2052HG regulates LMTK3 via EGR1, and LMTK3 regulates ERα stability via the PKC/MEK/ERK/RSK1 axis. These results reveal a direct role of MIR2052HG in LMTK3 regulation and raise the possibilities of targeting MIR2052HG or LMTK3 in ERα-positive breast cancer.

The online version of this article (10.1186/s13058-019-1130-3) contains supplementary material, which is available to authorized users.

• Aromatase inhibitor
• EGR1
• ERα
• LMTK3
• Lon noncoding RNA
• MIR2052HG
• PKC

• Diagnosis
• long non-coding RNA
• PCAT-1
• prognosis
• survival

• Biomarkers, Tumor/genetics
• Humans
• Neoplasms/genetics
• Neoplasms/pathology
• Prognosis
• RNA, Long Noncoding/genetics

Oxidized low‐density lipoprotein (ox‐LDL) can damage vascular endothelial cells and cause atherosclerosis, but its epigenetic regulatory mechanism has not been fully elucidated. We show that ox‐LDL induced significant apoptosis and loss of function in human umbilical vascular endothelial cells (HUVECs). At the same time, ox‐LDL significantly decreased the expression of Hippo–YAP/ZAP (Yes‐associated protein/YLP motif–containing 1) pathway proteins as compared to that of the control. The luciferase reporter system confirmed that microRNA (miR)‐496 silenced YAP gene expression by binding to its 3′ untranslated region (3′ UTR). Ox‐LDL–treated miR‐496 overexpression HUVECs had a higher apoptosis rate and more severe dysfunction compared to the control cells. This in‐depth study shows that ox‐LDL inhibits YAP protein expression by inducing miR‐496 expression, leading to its inability to enter the nucleus, thereby losing its function as a transcriptional cofactor for activating the downstream genes. Our findings reveal that, through epigenetic modification, ox‐LDL can inhibit the normal expression of Hippo–YAP/ZAP pathway proteins via miR‐496 expression and induce vascular endothelial cell dysfunction.

• Hippo-YAP/ZAP pathway
• miR-496
• oxidized low-density lipoprotein
• vascular endothelial cell

HER3 is the third member of the human epidermal growth factor receptor (HER/EGFR) family, and unlike its other family members, is unique due to its minimal intrinsic kinase activity. As a result, HER3 has to interact with another receptor tyrosine kinase (RTK), such as EGFR or HER2, in order to activate the PI-3 K/Akt, MEK/MAPK, Jak/Stat pathways, as well as Src kinase. Over-expression of HER3 in various human cancers promotes tumor progression by increasing metastatic potential and acting as a major cause of treatment failure. Effective inhibition of HER3, and/or the key downstream mediators of HER3 signaling, is thought to be required to overcome resistance and enhance therapeutic efficacy. To date, there is no known HER3-targeted therapy that is approved for breast cancer, with a number of anti-HER3 antibodies current in various stages of development and clinical testing. Recent data suggests that the epigenetic strategy of using a histone deacetylase (HDAC) inhibitor, or functional cooperative miRNAs, may be an effective way to abrogate HER3 signaling. Here, we summarize the latest advances in our understanding of the mechanism of HER3 signaling in tumor progression, with continuing research towards the identification of therapeutic anti-HER3 antibodies. We will also examine the potential to develop novel epigenetic approaches that specifically target the HER3 receptor, along with important key downstream mediators that are involved in cancer treatment.

• Cell signaling
• Epigenetic approach
• HER3
• Targeted therapy
• miRNA

There is an urgent need to identify new molecular targets for treatment of osteosarcoma. Circular RNAs are a class of endogenous RNAs that are extensively found in mammalian cells and exert critical functions in the regulation of gene expression, but in osteosarcoma the underlying molecular mechanism of circular RNAs remain poorly understood. Here we assessed the tumorigenesis properties of a circular RNA, circFAT1 in osteosarcoma.

The effects of circFAT1/miR-375/YAP1 was evaluated on human osteosarcoma cells growth, apoptosis, migration, invasion and tumorigenesis. Signaling pathways were analyzed by western blotting, qRT-PCR, fluorescence in situ hybridization, chromogenic in situ hybridization,RNA Binding Protein Immunoprecipitation and immunofluorescence. The consequence of circFAT1 short hairpin RNA combined or not with miR-375 sponge was evaluated in mice bearing 143B xenografts on tumor growth.

In this study, we observed significant upregulation of circFAT1 originating from exon 2 of the FAT1 gene in human osteosarcoma tissues and cell lines. Inhibition of circFAT1 effectively prevented the migration, invasion, and tumorigenesis of osteosarcoma cells in vitro and repressed osteosarcoma growth in vivo. Mechanistic studies revealed that circFAT1 contains a binding site for the microRNA-375 (miR-375) and can abundantly sponge miR-375 to upregulate the expression of Yes-associated protein 1. Moreover, inhibition of miR-375 reversed attenuation of cell proliferation, migration, and invasion, which was induced by circFAT1 knockdown, and therefore promoted tumorigenesis.

Our findings demonstrate a novel function of circFAT1 in tumorigenesis and suggest a new therapeutic target for the treatment of osteosarcoma.

The online version of this article (10.1186/s12943-018-0917-7) contains supplementary material, which is available to authorized users.

• Osteosarcoma
• YAP
• circFAT1
• circular RNA
• miR-375

• Copy number variation
• Long noncoding RNA
• Nasopharyngeal carcinoma
• Progression
• YY1

HER3 belongs to the human epidermal growth factor receptor (HER) family which also includes HER1/EGFR/erbB1, HER2/erbB2, and HER4/erbB4. As a unique member of the HER family, HER3 lacks or has little intrinsic tyrosine kinase activity. It frequently co-expresses and forms heterodimers with other receptor tyrosine kinases (RTKs) in cancer cells to activate oncogenic signaling, especially the PI-3K/Akt pathway and Src kinase. Elevated expression of HER3 has been observed in a wide variety of human cancers and associates with a worse survival in cancer patients with solid tumors. Studies on the underlying mechanism implicate HER3 expression as a major cause of treatment failure in cancer therapy. Activation of HER3 signaling has also been shown to promote cancer metastasis. These data strongly support the notion that therapeutic inactivation of HER3 and/or its downstream signaling is required to overcome treatment resistance and improve the outcomes of cancer patients.

• ADCC, antibody-dependent cell-mediated cytotoxicity
• Ab, antibody
• Cell signaling
• Dimerization
• EGFR, epidermal growth factor receptor
• EMT, epithelial-mesenchymal transition
• FDA, Food and Drug Administration
• HER, Human epidermal growth factor receptor
• HER3
• HRG, heregulin
• IGF-1R, insulin-like growth factor-I receptor
• MAPK, mitogen-activated protein kinase
• MEK, MAPK kinase
• NSCLC, non-small cell lung cancer
• OS, overall survival
• PI-3K, phosphoinositide 3-kinase
• RTK, receptor tyrosine kinase
• TKI, tyrosine kinase inhibitor
• Targeted therapy
• Therapeutic resistance
• Tumor metastasis
• lncRNA, long ncRNA
• miRNA, microRNA
• ncRNA, noncoding RNA

• Bone metastasis
• Cancer therapeutics
• Osteogenesis
• Osteolysis
• Wnt signaling

• baicalein
• breast cancer
• long noncoding RNA
• microRNA
• progression

Hepatocellular carcinoma (HCC) is one of the most prevalent subtypes of liver cancer worldwide. LncRNAs have been demonstrated to be associated with the progression of HCC, but a systematic identification and characterization of their clinical roles and molecular mechanisms in HCC has not been conducted. In this study, the aberrantly expressed lncRNAs in HCC tissues were analyzed based on TCGA RNA-seq data. 1162 lncRNAs were found to be aberrantly expressed in HCC tissues, including 232 down-regulated lncRNAs and 930 up-regulated lncRNAs. The top 5 lncRNAs with the highest diagnostic accuracy were further analyzed to evaluate their clinical value and potential mechanism in HCC. Kaplan-Meier curves showed that higher expressions of DDX11-AS1 and AC092171.4 were in correlation with poorer survival in HCC patients. Significant difference was also observed when comparing the expression levels of DDX11-AS1 and SFTA1P in different clinical parameters (p < 0.05). GO analysis showed that genes regulated by the 5 lncRNAs were enriched in certain pathways, such as PI3K pathway. Moreover, GSEA analysis on the expression of DDX11-AS1 showed that DDX11-AS1 affected the gene expressions involved in HCC proliferation, differentiation and cell cycle, indicating an essential role of DDX11-AS1 in hepatocarcinogenesis.

• TUSC7
• prognosis
• tumor suppressor
• tumorigenesis

• alzheimer's disease
• angiogenesis
• cancer stem cells
• epithelial-to-mesenchymal transition
• fgf
• myeloid-derived suppressor cells
• notch
• regulatory t cells
• tumor microenvironment
• wnt5a

• Animals
• Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
• Colorectal Neoplasms, Hereditary Nonpolyposis/metabolism
• Colorectal Neoplasms, Hereditary Nonpolyposis/therapy
• Endometrial Neoplasms/genetics
• Endometrial Neoplasms/metabolism
• Endometrial Neoplasms/therapy
• Female
• Humans
• Intellectual Disability/metabolism
• Intellectual Disability/therapy
• Male
• Mutation
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Prostatic Neoplasms/genetics
• Prostatic Neoplasms/metabolism
• Prostatic Neoplasms/therapy
• Wnt Signaling Pathway/genetics

Taurine up-regulated gene 1 (TUG1) is a long non-coding RNA (lncRNA), has been reported that be dysregulated in various tumors, involved in proliferation and apoptosis in a variety of tumor cells. To detect the clinical significance of TUG1 expression in tumor patients, we carried out current systematic review and meta-analysis investigating its relation with the prognosis and clinicopathological features of cancers. A total of 15 studies comprise 1560 patients were analyzed. The pooled results showed that no significant relationship between high TUG1 expression and overall survival (OS) (HR = 1.28, 95% CI: 0.96–1.69, P = 0.091) in various tumors. In the subgroup analysis by cancer type, elevated TUG1 expression was associated with poorer survival in cancer patients with high TUG1 expression subgroup but better survival in patients with low TUG1 expression subgroup. Over-expression of TUG1 associated with significantly unfavorable survival for bladder cancer (HR=2.67, 95% CI: 1.47–4.87, P = 0.001). Up-regulation of TUG1 correlated with distant metastasis (DM) (OR = 4.22, 95% CI: 2.66–6.70, P < 0.001) and tumor differentiation (OR = 2.45, 95% CI: 1.28–4.70, P = 0.007), but failed to show inline to gender (OR = 1.04, 95% CI: 0.77–1.42, P = 0.774), age (OR = 0.75, 95% CI: 0.51–1.10, P = 0.136), lymph node metastasis (LNM) (OR = 1.45, 95% CI: 0.85–2.50, P = 0.177), and TNM stage (OR = 0.55, 95% CI: 0.17–1.81, P = 0.326). The overall results suggest lncRNA TUG1 may be a useful prognostic biomarker in cancer patients.

• TUG1
• cancer
• clinical outcome
• prognosis

The growth arrest-specific 5 transcript (GAS5) is a long non-coding RNA (lncRNA) involved in the control of cell cycle progression and apoptosis in a wide variety of cells. To determine the clinical value of GAS5 expression in cancer patients, we performed a systematic review and meta-analysis exploring its association with the diagnosis, prognosis, and clinicopathological characteristics of cancer. Ten articles on prognosis, 15 on clinicopathology, and 5 on diagnosis were analyzed. Overall results showed that decreased GAS5 expression associated with unfavorable overall survival (OS) (HR = 2.50, 95%CI: 1.85–3.38, P < 0.001) and disease-free survival (DFS) (HR = 2.24, 95%CI: 1.58–3.18, P < 0.001) in several tumor types. Down-regulation of GAS5 correlated with poor recurrence-free survival (RFS) in hepatocellular carcinoma (HR = 2.40, 95%CI: 1.27–4.54, P = 0.007), and was associated with lymph node metastasis (OR = 1.92, 95% CI: 1.44–2.57, P < 0.001), distant metastasis (OR = 2.7, 95% CI: 1.05–6.97, P = 0.040), poor clinical stage (OR = 0.26, 95% CI: 0.18–0.38, P < 0.001), larger tumor size (OR = 3.21, 95% CI: 2.08–4.95, P < 0.001), and poor tumor differentiation (OR = 1.98, 95% CI: 1.40–2.80, P < 0.001). Pooled results of diagnostic data analysis showed that GAS5 exhibited a sensitivity of 0.76 and specificity of 0.64 for cancer diagnosis, and an area under the curve of 0.76 (95% CI: 0.72–0.80) indicated moderate diagnostic accuracy. This meta-analysis suggests GAS5 lncRNA may be a useful diagnostic and prognostic cancer biomarker, and may be especially useful for identifying patients prone to developing lymph node or distant metastasis.

• GAS5
• cancer
• clinical outcome
• diagnosis
• prognosis