• Cancer progression
• FOXO6
• Metabolic disorders
• PI3K/Akt pathway
• Therapeutic target

• Humans
• Animals
• Forkhead Transcription Factors/metabolism
• Forkhead Transcription Factors/genetics
• Neoplasms/metabolism
• Neoplasms/drug therapy
• Signal Transduction/drug effects
• Neurodegenerative Diseases/drug therapy
• Neurodegenerative Diseases/metabolism
• Metabolic Diseases/metabolism
• Metabolic Diseases/drug therapy
• Oxidative Stress/drug effects

• Cerebral ischemia–reperfusion
• Mff
• Mice
• Neuronal injury
• Norad
• Pum2

• Animals
• Reperfusion Injury/metabolism
• Reperfusion Injury/pathology
• RNA-Binding Proteins/metabolism
• RNA-Binding Proteins/genetics
• Mice
• Neurons/metabolism
• Neurons/pathology
• Male
• Brain Ischemia/metabolism
• Brain Ischemia/pathology
• Mitochondria/metabolism
• Mice, Inbred C57BL
• Infarction, Middle Cerebral Artery/metabolism
• Infarction, Middle Cerebral Artery/pathology
• Disease Models, Animal

• Apoptosis
• Cancer
• NORAD
• Proliferation
• lncRNAs

• Ferroptosis
• Glutathione peroxidase 4 (GPX4)
• Long non-coding RNA X-inactive-specific transcript (LncRNA-XIST)
• Lung adenocarcinoma

• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Humans
• Ferroptosis/genetics
• Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism
• Phospholipid Hydroperoxide Glutathione Peroxidase/genetics
• Adenocarcinoma of Lung/genetics
• Adenocarcinoma of Lung/pathology
• Adenocarcinoma of Lung/metabolism
• Lung Neoplasms/genetics
• Lung Neoplasms/pathology
• Lung Neoplasms/metabolism
• Gene Expression Regulation, Neoplastic
• Cell Proliferation
• Cell Line, Tumor
• Reactive Oxygen Species/metabolism
• Male
• Amino Acid Transport System y+/genetics
• Amino Acid Transport System y+/metabolism
• Female
• Gene Knockdown Techniques
• Middle Aged

• Angiogenesis
• Cardiovascular disease
• Circular RNA
• Exosome
• Long non-coding RNA
• MicroRNA
• Non-coding RNAs

• Humans
• Cardiovascular Diseases/genetics
• Cardiovascular Diseases/metabolism
• Cardiovascular Diseases/pathology
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism
• Neovascularization, Pathologic/genetics
• Neovascularization, Pathologic/metabolism
• Animals
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Circular/genetics
• RNA, Circular/metabolism
• Neovascularization, Physiologic/genetics
• Angiogenesis

• non-small-cell lung cancer
• cell death

• Key Research and Development Program of Hebei Province (No. 22377790D)

• Cancer stem cells
• Competing endogenous RNAs
• Micro-RNA
• ceRNA
• lncRNA

• Cancer
• Drug resistance
• Exosome
• GI cancer
• Non-coding RNA

• Humans
• Drug Resistance, Neoplasm/genetics
• Exosomes/metabolism
• Exosomes/genetics
• Gastrointestinal Neoplasms/genetics
• Gastrointestinal Neoplasms/drug therapy
• Gastrointestinal Neoplasms/pathology
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• RNA, Untranslated/genetics
• Antineoplastic Agents/therapeutic use
• Antineoplastic Agents/pharmacology
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Gene Expression Regulation, Neoplastic/drug effects

• Gastric cancer
• MAP2K7
• lncRNA PCED1B-AS1
• miR-3681-3p

• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Epithelial-Mesenchymal Transition/genetics
• Cell Line, Tumor
• Animals
• Mice
• Mice, Nude
• MAP Kinase Kinase Kinases/genetics
• MAP Kinase Kinase Kinases/metabolism
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Neoplasm Invasiveness
• Cell Movement
• Neoplasm Metastasis

• PWRd2021-02 Academic Leaders Training Program of Pudong Health Bureau of Shanghai
• No. 19411951505 the Fund from the Science and Technology Commission of Shanghai Municipality
• PWZxq2022-6 and PWYgf2021-2 Medical Discipline Construction Project of Pudong Health Committee of Shanghai

• Norad
• Pum2
• apoptosis
• neuron
• subarachnoid hemorrhage

• Mice
• Animals
• Subarachnoid Hemorrhage/metabolism
• Neuroprotection
• Disease Models, Animal
• Apoptosis/physiology
• RNA, Untranslated
• RNA-Binding Proteins/genetics

Gastric cancer (GC) is a malignant tumor with high morbidity and mortality. Expression of COL5A2 is significantly elevated in GC. Abnormal expression of noncoding RNAs (ncRNAs) have been found in GC, including microRNA (miRNA) and long noncoding RNA (lncRNA). Competing endogenous RNA network plays an important regulatory role in GC. However, its specific regulatory mechanism has not been elucidated.

To gain insight into the ncRNA regulatory mechanism and immune microenvironment related to COL5A2 in GC.

RNA sequencing data and clinical information from The Cancer Genome Atlas data portal were used to analyze the expressions of COL5A2, miRNA and lncRNA related to the prognosis of GC. Cox regression analysis and Kyoto Encyclopedia of Genes and Genomes analysis were performed to assess the risk factors and relevant function of COL5A2. StarBase was used to predict the interaction of miRNA–lncRNA or miRNA–mRNA in GC. The relationship between COL5A2, miR-144-3p and ENTPD1-AS1 were verified by dual luciferase reporter assay. The association of COL5A2 with immune cell infiltration were analyzed using the Tumor Immune Estimation Resource database and single sample gene set enrichment analysis. The expression of COL5A2 and macrophages in paired GC tissues were detected by immunohistochemical staining.

We verified that the upregulation of COL5A2 expression was associated with the prognosis of GC and was an independent risk factor for GC. miR-144-3p was downregulated and correlated with the prognosis of GC. miR-144-3p regulated the expression of COL5A2 through direct interaction with COL5A2. ENTPD1-AS1 was elevated in GC and competitively bound to miR-144-3p, thus inhibiting the expression of miR-144-3p. ENTPD1-AS1 enhanced the expression of COL5A2 through sponging miR-144-3p. Compared to paired normal tissue, COL5A2 expression was upregulated at the protein level, especially in the middle and late stages of GC. The high expression of COL5A2 was positively linked to macrophage infiltration in GC.

COL5A2 regulated by ENTPD1-AS1–miR-144-3p was associated with poor prognosis and macrophage infiltration in GC. This could be a new biomarker and therapeutic target in GC.

• COL5A2
• Noncoding RNAs
• Macrophage infiltration
• Prognosis
• Gastric cancer

• Cancer
• Cancer therapy
• Chemo-resistance
• FOXO
• Forkhead box dependent transcription factors
• MicroRNAs

• biomarkers
• gastrointestinal neoplasms
• molecular targeted therapy
• neutrophil extracellular traps
• quantitation

• Humans
• Extracellular Traps/metabolism
• COVID-19/pathology
• Neutrophils
• Gastrointestinal Neoplasms/metabolism
• Thrombosis/metabolism
• Tumor Microenvironment

• gastric cancer
• gastric carcinoma
• microRNAs
• single nucleotide polymorphism

• Humans
• Polymorphism, Single Nucleotide/genetics
• Stomach Neoplasms/genetics
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Genetic Predisposition to Disease/genetics
• Case-Control Studies

• Biomarker
• FOXOs
• Gastric cancer
• PTMs
• Therapeutic target

Gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer-related deaths worldwide. Neutrophil extracellular traps (NETs) can enhance the invasion of GC cells and are associated with poor prognosis in patients. However, its mechanism of action is not completely understood.

The content of NETs in the peripheral blood of patients with GC was detected by enzyme-linked immunosorbent assay. GC AGS cells were treated with or without NETs for 24 h. High-throughput RNA sequencing was performed to screen differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Real-time polymerase chain reaction (PCR) was used to verify gene expression. A competing endogenous RNA (ceRNA) regulatory network was constructed. Modules were screened using the molecular complex detection (MCODE) plug-in. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the genes in the network. The role and clinical significance of the lncRNA NEAT1-related signaling pathway were validated.

The content of NETs in the patients with GC was significantly higher than that in healthy controls and was also higher in patients with high-grade (stages III and IV) GC. NETs promoted the invasion of AGS cells. A total of 1,340 lncRNAs, 315 miRNAs, and 1,083 mRNAs were differentially expressed after NET treatment. The expression of five genes was validated using real-time PCR, which were in accordance with the RNA sequencing results. A ceRNA regulatory network was constructed with 1,239 lncRNAs, 310 miRNAs, and 1,009 mRNAs. Four genes (RAB3B, EPB41L4B, ABCB11, and CCDC88A) in the ceRNA network were associated with patient prognosis, with RAB3B being the most prominent and with signaling among the lncRNA NEAT1, the miRNA miR-3158-5p, and RAB3B. NEAT1 was upregulated in AGS cells after NET treatment. RNA interference of NEAT1 inhibited the invasion of AGS cells induced by NETs, inhibited miR-3158-5p expression, and promoted RAB3B expression. NEAT1 and RAB3B expression were positively correlated in patients with GC. Furthermore, RAB3B was upregulated and miR-3158-5p was downregulated in GC tissues compared with adjacent normal tissues, which was also associated with cancer stage.

This study provides a comprehensive analysis of differentially expressed genes in NET-treated GC cells and validated the clinical significance of NEAT1-related signaling.

• National Natural Science Foundation of China

In recent years, microRNAs (miRNAs) have attracted much attention because of their prominent role in cancer. An increasing number of studies have shown that miRNAs play an important role in a variety of tumors. miR-608 has been reported to be decreased in cancers, especially in solid tumors. miR-608 is regarded as a tumor suppressor, which has been verified through a large number of experiments both in vivo and in vitro. miR-608 participates in many biological processes, including cell proliferation, invasion, migration, and apoptosis, by inhibiting transmembrane proteins and many signaling pathways. Here, we summarize the expression profile and biological functions and mechanism of miR-608, suggesting that miR-608 is an ideal diagnostic and prognostic biomarker and a treatment target for cancer.

• biomarker
• cancer
• miR-608
• molecular mechanism
• tumor suppressor

Non-coding RNAs are a type of genetic material that doesn’t make protein, but performs diverse regulatory functions. In prostate cancer, most treatments target proteins, and resistance to such therapies is common, leading to disease progression. Targeting non-coding RNAs may provide alterative treatment options and potentially overcome drug resistance. Major types of non-coding RNAs include tiny ‘microRNAs’ and much longer ‘long non-coding RNAs’. Scientific studies have shown that these form a major part of the human genome, and play key roles in altering gene activity and determining the fate of cells. Importantly, in cancer, their activity is altered. Recent evidence suggests that microRNAs and long non-coding RNAs play important roles in controlling response to DNA damage. In this review, we explore how different types of non-coding RNA interact to control cell DNA damage responses, and how this knowledge may be used to design better prostate cancer treatments and tests.

It is increasingly appreciated that transcripts derived from non-coding parts of the human genome, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are key regulators of biological processes both in normal physiology and disease. Their dysregulation during tumourigenesis has attracted significant interest in their exploitation as novel cancer therapeutics. Prostate cancer (PCa), as one of the most diagnosed malignancies and a leading cause of cancer-related death in men, continues to pose a major public health problem. In particular, survival of men with metastatic disease is very poor. Defects in DNA damage response (DDR) pathways culminate in genomic instability in PCa, which is associated with aggressive disease and poor patient outcome. Treatment options for metastatic PCa remain limited. Thus, researchers are increasingly targeting ncRNAs and DDR pathways to develop new biomarkers and therapeutics for PCa. Increasing evidence points to a widespread and biologically-relevant regulatory network of interactions between lncRNAs and miRNAs, with implications for major biological and pathological processes. This review summarises the current state of knowledge surrounding the roles of the lncRNA:miRNA interactions in PCa DDR, and their emerging potential as predictive and diagnostic biomarkers. We also discuss their therapeutic promise for the clinical management of PCa.

• DNA damage
• DNA damage response
• DNA repair
• long non-coding RNA
• microRNA
• non-coding RNA
• prostate cancer

• Apoptosis
• Biomarker
• Gastric cancer
• LncRNA
• NORAD
• Suppression

Hepatoblastoma is the most common liver tumor. Recent research has found that long non-coding (lnc)RNAs are involved in multiple types of cancers, but the potential mechanism of lncRNA MIR210HG in hepatoblastoma remains unknown. The present study explored the molecular mechanism of MIR210HG in hepatoblastoma progression.

The cell counting kit-8 was used to detect cell viability, and Transwell assays assessed cell migration and invasion. Luciferase reporter assays showed the relationship between MIR210HG and microRNA (miR)-608 and between miR-608 and forkhead box O6 (FOXO6). Functional tests were verified in vivo by a tumor xenograft model. The expression of MIR210HG, miR-608, FOXO6, E-cadherin, N-cadherin, and vimentin was determined by quantitative reverse transcription polymerase chain reaction and western blotting.

MIR210HG was shown to be highly expressed in hepatoblastoma tissues and cell lines. Knockdown of MIR210HG reduced proliferation, migration, and invasion in liver cancer cells, and suppressed tumor growth in vivo. MIR210HG competitively combined with miR-608, and miR-608 decreased FOXO6 expression.

Our study demonstrated that knockdown of MIR210HG inhibits hepatoblastoma development through binding to miR-608 and downregulating FOXO6. Our results provide novel insights for hepatoblastoma treatment involving the MIR210HG–miR608–FOXO6 axis.

• MIR210HG
• cell invasion
• cell migration
• cell proliferation
• forkhead box O6
• hepatoblastoma
• microRNA-608

• IL-33
• Lncrna NORAD
• carcinoma-associated fibroblasts
• gastric cancer
• miR-496

• Base Sequence
• Cancer-Associated Fibroblasts/metabolism
• Cancer-Associated Fibroblasts/pathology
• Carcinogenesis/genetics
• Carcinogenesis/pathology
• Cell Line, Tumor
• Cell Proliferation/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Interleukin-33/metabolism
• Male
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• Models, Biological
• Neoplasm Invasiveness
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Up-Regulation/genetics

• Apoptosis
• Bladder cancer
• Gemcitabine resistance
• NORAD
• Proliferation

• Drug resistance
• Gastrointestinal cancers
• LncRNA
• MiRNAs

• RHO GTPases
• carcinogenesis
• lncRNAs
• miRNAs
• signal transduction
• sponge effect

• GeNeRARe(01GM1902C) Federal Ministry of Education and Research
• NSEuroNet (01GM1621B) the European Network on Noonan Syndrome and Related Disorders

Gastric cancer (GC) is the fifth most diagnosed cancer and the third leading cause of cancer-related death worldwide. Although progress has been made in diagnosis, surgical resection, systemic chemotherapy, and immunotherapy, patients with GC still have a poor prognosis. The overall 5-year survival rate in patients with advanced GC is less than 5%. The FOXO subfamily, of the forkhead box family of transcription factors, consists of four members, FOXO1, FOXO3, FOXO4, and FOXO6. This subfamily plays an important role in many cellular processes, such as cell cycle, cell growth, apoptosis, autophagy, stress resistance, protection from aggregate toxicity, DNA repair, tumor suppression, and metabolism, in both normal tissue and malignant tumors. Various studies support a role for FOXOs as tumor suppressors based on their ability to inhibit angiogenesis and metastasis, and promote apoptosis, yet several other studies have shown that FOXOs might also promote tumor progression in certain circumstances. To elucidate the diverse roles of FOXOs in GC, this article systematically reviews the cellular functions of FOXOs in GC to determine potential therapeutic targets and treatment strategies for patients with GC.

• FOXO
• Gastric cancer
• Regulation
• Therapy
• Expression

• NORAD
• cancer
• carcinogenesis
• expression
• lncRNA

Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC’s mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC’s ceRNA network.

• competitive endogenous RNA
• gastric cancer
• non-coding RNAs

• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Helicobacter pylori
• Humans
• MicroRNAs/genetics
• Microarray Analysis
• Pseudogenes
• RNA, Circular/genetics
• RNA, Long Noncoding/genetics
• RNA, Messenger/genetics
• RNA, Untranslated/genetics
• Response Elements
• Stomach Neoplasms/genetics

Gastric cancer (GC) is ranked the fourth leading cause of cancer-related death, with an over 75% mortality rate worldwide. In recent years, miR-299-3p has been identified as a biomarker in multiple cancers, such as acute promyelocytic leukemia, thyroid cancer, and lung cancer. However, the regulatory mechanism of miR-299-3p in GC cell progression is still largely unclear. Cell viability and apoptosis tests were performed by CCK8 and flow cytometry assay, respectively. Transwell assay was recruited to examine cell invasion ability. The interaction between miR-299-3p and PAX3 was determined by the luciferase reporter system. PAX3 protein level was evaluated by western blot assay. The expression of miR-299-3p was downregulated in GC tissues and cell lines (MKN-45, AGS, and MGC-803) compared with the normal tissues and cells. Besides, overexpression of miR-299-3p significantly suppressed proliferation and invasion and promoted apoptosis in GC. Next, we clarified that PAX3 expression was regulated by miR-299-3p using a luciferase reporter system, qRT-PCR, and western blot assay. Additionally, downregulation of PAX3 repressed GC cell progression. The rescue experiments indicated that restoration of PAX3 inversed miR-299-3p-mediated inhibition on cell proliferation and invasion. miR-299-3p suppresses cell proliferation and invasion as well as induces apoptosis by regulating PAX3 expression in GC, representing desirable biomarkers for GC diagnosis and therapy.

• GC biomarkers
• GC therapy
• PAX3
• gastric cancer
• miR-299-3p

Substantial researches indicated that long non-coding RNAs (lncRNAs) exerted profound effects on chemo-resistance in cancer treatment. Nonetheless, the role of NORAD in non-small-cell lung cancer (NSCLC) remains unclear. In the present study, we chose NSCLC cell lines H446 and A549 to explore the function of non-coding RNA activated damage (NORAD) in response to cisplatin (DDP) resistance of NSCLC. Experimental data manifested that NORAD was up-regulated in DDP-resistant NSCLC tissues and cells. NSCLC patients with high NORAD expression suffered a poor prognosis. NORAD knockdown resensitized H446/DDP and A549/DDP to DDP. Besides, NORAD acted as a molecular sponge of miR-129-1-3p. MiR-129-1-3p showed a low level of expression in DDP-resistant NSCLC tissues. Moreover, miR-129-1-3p overexpression impaired DDP resistance in H446/DDP and A549/DDP cells. SOX4 was the downstream target of miR-129-1-3p. Especially, SOX4 overexpression offset the effects of NORAD silence on H446/DDP and A549/DDP cells resistance to DDP. NORAD knockdown resensitized H446/DDP and A549/DDP to DDP in NSCLC via targeting miR-129-1-3p/SOX4 axis, offering a brand-new target for NSCLC chemo-resistance.

• NORAD
• SOX4
• chemo-resistance
• miR-129-1-3p
• non-small-cell lung cancer

• NORAD
• clinicopathological features
• meta-analysis
• prognosis
• tumor

• Atherosclerosis
• Krüppel-like factor 5
• Long non-coding RNA activated By DNA damage
• MicroRNA-495-3p
• Plaque formation

• Circ_0081146
• Gastric cancer
• HMGB1
• MiR-144

• LncRNA NORAD
• OPG/RANK/ RANKL pathway
• Proliferation
• Steroid-induced osteonecrosis of the femoral head
• miR-26a-5p

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that causes scarring of the lungs. The disease is associated with the usual interstitial pneumonia pattern, which was not yet fully recapitulated by an animal model. Therefore, the disease is considered ‘human specific’. miRNA-608 is a primate specific miRNA with many potential targets, such CdC42 and Interlukin-6 (IL-6) that were previously implicated in IPF pathology.

To test miR-608 expression and its targets in IPF patient samples.

RNA was extracted from Formalin fixed paraffin embedded tissue sections (N = 18). miRNA-608 and Cdc42 and IL-6 levels were analyzed by qPCR. Acetylcholinesterase (AChE) is another target of miRNA-608. Its’ rs17228616 allele has a single-nucleotide polymorphism causing weakened miR-608 interaction (C2098A). Thus, DNA was extracted from whole blood samples from 56 subjects with fibrosing interstitial lung disease and this region was sequenced for assessment of rs17228616 allele polymorphism.

miR-608 is significantly overexpressed in IPF samples in comparison with controls (p < 0.05). Cdc42 and IL-6 levels were lower in the IPF patient samples compared with control samples (p < 0.001 and p < 0.05, respectively). The frequency of the rs17228616 minor A-allele was 17/56 (30.4%) with all patients being heterozygous. This result is significant vs. the published Israeli cohort of healthy individuals, which reported 17% prevalence of this allele in healthy control volunteers (p = 0.01, OR = 2.1, CI 95% [1.19–3.9]).

miR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.

• CdC42
• ILD
• IPF
• SNP
• microRNA

• Cancer
• Long non-coding RNA
• NORAD
• miRNA

Non-coding RNA-activated by DNA damage (NORAD), a novel identified lncRNA, was found to be aberrantly expressed in various types of cancer. This meta-analysis was performed to evaluate the value of lncRNA NORAD as a prognostic biomarker in human cancers.

We searched PubMed, Web of Science, PMC, and Embase databases thoroughly for eligible literatures. Studies which explored the relationship of lncRNA NORAD expression with clinical outcomes in human cancers were included in our meta-analysis. Review Manager version 5.3 and Stata SE 12.0 were used to perform the data analyses.

Our meta-analysis results indicated that cancer patients with high lncRNA NORAD expression tended to have unfavorable overall survival (OS) (HR = 1.67; 95% CI, 1.44-1.95; P < 0.00001). Moreover, elevated lncRNA NORAD expression showed a significant relationship with poor tumor grade (OR = 1.61; 95% CI, 1.01-2.56; P = 0.05) and more lymph node metastasis (LNM) (OR = 2.66; 95% CI, 1.60-4.43; P = 0.0002).

LncRNA NORAD could serve as a valuable biomarker to predict poor prognosis and LNM in various human tumors.

• LncRNA
• NORAD
• cancer
• meta-analysis
• prognosis

•

BLACAT1 promotes cell proliferation, migration and invasion, and dampens cell apoptosis in OS.

Osteosarcoma is the most common type of bone malignancy. Increasing evidence indicated that long non-coding RNAs (lncRNAs) possess multiple functions in the development of cancer and can be used as indicators of prognosis and diagnosis. LncRNA BLACAT1 has been found to promote the proliferation of breast cancer cells. However, the role of BLACAT1 in osteosarcoma remains largely unknown.

QRT-PCR analysis was employed to evaluate mRNA expressions. Western blot was performed to measure relevant protein level. Colony formation and EdU assays were conducted to certify proliferative ability. TUNEL assay was finalized to assess apoptotic cells. Wound-healing and transwell assays were utilized for the exploration of migrating and invasive abilities. The subcellular distribution of BLACAT1 was studied by nucleus-cytoplasm separation assay. Relevant mechanical experiments were combined to elucidate molecular relationship between molecules.

BLACAT1 was highly expressed in osteosarcoma. BLACAT1 promoted the proliferation and migration of osteosarcoma cells. BLACAT1 acted as a sponge for miR-608 to augment the expression of Sex determining region Y-box protein 12 (SOX12), the direct target of miR-608. Further, inhibiting miR-608 recovered the repressive effect of silenced BLACAT1 on the malignant behaviors of osteosarcoma cells.

This study highlighted the contribution of BLACAT1/miR-608/SOX12 axis to the progression of osteosarcoma, suggesting novel targets for osteosarcoma therapy.

• ANOVA, analysis of variance
• ATCC, American type culture collection
• BLACAT1
• DMEM, Dulbecco’s modified Eagle’s medium
• FBS, fetal bovine serum
• FISH, Fluorescence in situ hybridization
• HRP, horseradish peroxidase
• Mut, mutant
• OS, osteosarcoma
• Osteosarcoma
• PVDF, polyvinylidene fluoride
• RIPA, radioimmunoprecipitation assay
• RT-qPCR, RNA extraction and quantitative real-time polymerase chain reaction
• SD, standard deviation
• SDS-PAGE, sulphate-polyacrylamide gel electrophoresis
• SOX, sex-determining region Y (SRY)-box
• SOX12
• SOX12, sex determining region Y-box protein 12
• WT, wild-type
• ceRNAs, competing endogenous RNAs
• lncRNAs, long non-coding RNAs
• mRNA, messenger RNA
• miR-608
• miRNAs, microRNAs

We aimed to investigate the functions of long non-coding RNA (lncRNA) non-coding RNA activated by DNA damage (NORAD) in glioma and identify the potential mechanisms.

The expression of NORAD and AKR1B1 in human glioma cell lines were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Then, cell proliferation, invasion, and migration were tested by Cell Counting Kit-8 (CCK-8), colony formation assay, Transwell, and scratch wound healing assay after NORAD silencing. Meanwhile, western blotting was utilized to measure the expression of migration-related proteins. Apoptosis of glioma cells was detected using flow cytometry and apoptosis-related proteins expression was determined. Moreover, the correlation between NORAD and AKR1B1 was verified by RNA-binding protein immunoprecipitation (RIP assay). After co-transfection with AKR1B1 overexpressed plasmid and NORAD siRNA, cell proliferation, invasion, migration, and apoptosis were examined again. Furthermore, the expression of proteins in extracellular signal-regulated kinase (ERK) signaling was tested using western blotting.

The results revealed that NORAD and AKR1B1 were highly expressed in glioma cells. NORAD silencing inhibited proliferation, invasion and migration but promoted apoptosis of glioma cells, accompanied by the expression changes of migration- and apoptosis-related proteins. However, after co-transfection with AKR1B1 pcDNA3.1 in NORAD silencing cells, the effects of NORAD silencing on proliferation, invasion, migration, and apoptosis were attenuated. Consistently, the expression of phosphorylated ERK (p-ERK) was decreased after NORAD silencing, which were reversed following AKR1B1 overexpression.

These findings demonstrated that NORAD silencing suppressed proliferation, invasion, and migration and boosted apoptosis of glioma cells via downregulating the AKR1B1 expression, which may provide a potential therapeutic target for glioma treatment.

• Biological function
• Biomarker
• Gastric cancer (GC)
• Long non-coding RNA (lncRNA)
• Therapeutic application

• Colorectal cancer stem-like cells
• LINC00657
• Metastasis
• miR-203a

• HDAC8
• NORAD
• Neuroblastoma
• miR-144-3p

Long noncoding RNAs (lncRNAs) play important roles in the development of vascular diseases. However, the effect of lncRNA NORAD on atherosclerosis remains unknown. This study aimed to investigate the effect NORAD on endothelial cell injury and atherosclerosis. Ox-LDL-treated human umbilical vein endothelial cells (HUVECs) and high-fat-diet (HFD)-fed ApoE^−/− mice were used as in vitro and in vivo models. Results showed that NORAD-knockdown induced cell cycle arrest in G0/G1 phase, aggravated ox-LDL-induced cell viability reduction, cell apoptosis, and cell senescence along with the increased expression of Bax, P53, P21 and cleaved caspase-3 and the decreased expression of Bcl-2. The effect of NORAD on cell viability was further verified via NORAD-overexpression. NORAD- knockdown increased ox-LDL-induced reactive oxygen species, malondialdehyde, p-IKBα expression levels and NF-κB nuclear translocation. Proinflammatory molecules ICAM, VCAM, and IL-8 were also increased by NORAD- knockdown. Additionally, we identified the strong interaction of NORAD and IL-8 transcription repressor SFPQ in HUVECs. In ApoE^−/− mice, NORAD-knockdown increased the lipid disorder and atherosclerotic lesions. The results have suggested that lncRNA NORAD attenuates endothelial cell senescence, endothelial cell apoptosis, and atherosclerosis via NF-κB and p53–p21 signaling pathways and IL-8, in which NORAD-mediated effect on IL-8 might through the direct interaction with SFPQ.

• IL-8
• NORAD
• cell apoptosis
• cell senescence
• ox-LDL

Gastric cancer (GC) is one of the most frequently occurring life-threatening malignancies worldwide. Due to its high mortality rate, the discovery of putative biomarkers that may be sensitive and specific to GC is of seminal importance. Long non-coding RNAs (lncRNAs) are non-translatable RNAs whose transcript length exceeds 200 base pairs. The dysregulation of lncRNA expression plays a key role in tumorigenesis and development. In the present study, the expression profiles of lncRNAs, microRNAs and mRNAs of 361 GC tissues (and 32 normal gastric tissues) were downloaded from The Cancer Genome Atlas database. Furthermore, differentially expressed RNAs were analyzed by the DEseq package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses confirmed some significant dysregulated signaling pathways and target RNAs. As a result, an lncRNA-associated competing endogenous RNA (ceRNA) network was constructed. Kaplan-Meier analysis of the differentially expressed RNAs associated with GC pathogenesis confirmed that the lncRNAs PVT1, HAND2-AS1 and ZNF667-AS1 were potentially associated with the prognosis of GC (P<0.05). The present study suggests the mechanism of ceRNA networks in GC, and further demonstrates that aberrant lncRNA expression may be used as an effective diagnostic tool (or target) for the prognosis of GC.

• HAND2-AS1
• PVT1
• ZNF667-AS1
• competing endogenous RNA
• gastric cancer

• PCAT18
• PI3K/AKT signaling pathway
• gastric cancer
• miR-107

• ELANE
• Sepsis
• miR-608
• microRNAs
• microarray

• Akt/mTOR
• gastric cancer
• lncRNA NORAD
• miR-214

Prostate cancer (PCA) is the deadliest urological disease affecting men worldwide. Long noncoding RNA activated by DNA damage (NORAD) levels are increased in many cancer types, and induce cancer cell progression. However, little is known about the biological functions of NORAD in PCA.

In this work, the roles of NORAD in cell proliferation, migration, and apoptosis were examined by Cell Counting Kit-8, scratch wound, and annexin V-fluorescein isothiocyanate/propidium iodide staining assays, respectively, in PCA cell lines. Knockdown of NORAD was achieved by small interfering (si)RNA in PCA cell lines, and quantitative real-time PCR was used to detect the expression of NORAD.

Cell proliferation and migration rates were significantly lower in the siNORAD group than in the wild-type group, while the apoptosis level was significantly higher in the siNORAD group compared with the wild-type group.

These results suggest that NORAD promotes the proliferation and migration of PCA cells and inhibits their apoptosis.

• NORAD
• apoptosis
• long non-coding RNA
• migration
• proliferation
• prostate cancer