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Ferroptosis is a newly-discovered cell death mechanism involved in the progression of various tumors, the role of noncoding RNAs (ncRNAs) in it was relatively less explored. This study identified the low levels of a recently studied long noncoding RNA (lncRNA), A2M-AS1, in pancreatic cancer and suggested its positive correlation with the overall survival time of patients with pancreatic cancer. A2M-AS1 was mainly localized in the cytoplasm, inhibiting the cellular proliferation, migration, and invasion as well as the tumor growth of the pancreatic cancer cells. Moreover, the Erastin-induced ferroptosis increased the expression levels of A2M-AS1. The overexpression of A2M-AS1 promoted ferroptosis in the pancreatic cancer, which was inhibited by the silencing of A2M-AS1. Mechanically, A2M-AS1 could directly interact with the poly (rC) binding protein 3 (PCBP3), which plays an important role in the process of iron metabolism, thereby promoting the ferroptosis in pancreatic cancer. In addition, the A2M-AS1/PCBP3 axis could facilitate the p38 activation and inhibit the phosphorylation of the AKT–mTOR signaling pathway; all these participate in regulating ferroptosis. In conclusion, the regulation of ferroptosis by targeting the A2M-AS1/PCBP3 axis might provide a novel target for the treatment of pancreatic cancer in the future. Implications: A2M-AS1 might be a potential novel therapeutic target for patients with pancreatic cancer in the future.

To explore the potential of long noncoding RNA (lncRNA) as a diagnostic and prognostic biomarker for patients with sepsis.Literature was obtained from seven databases. Relevant data were examined by combining sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic orders ratio (DOR), and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve with their corresponding 95% confidence intervals (CI) using a bivariate model.Seventeen works of literature were included for meta-analysis. The meta-analysis determined that combined SEN was 0.76 (95% C.I.: 0.69-0.82), combined SPE was 0.84 (95% C.I.: 0.79-0.88), combined PLR was 4.81 (95% C.I.: 3.70-6.25), combined NLR was 0.28 (95% C.I.: 0.22-0.36), combined DOR was 17.02 (95% C.I.: 11.96-24.22), and AUC was 0.88 (95% C.I.: 0.84-0.90), however, for prognostic meta-analysis, combined SEN was 0.82 (95% C.I.: 0.73-0.86), combined SPE was 0.69 (95% C.I.: 0.54-0.81), combined PLR was 2.69 (95% C.I.: 1.82-3.97), combined NLR was 0.25 (95% C.I.: 0.10-0.35), combined DOR was 10.63 (95% C.I.: 7.13-15.87), and AUC was 0.84 (95% C.I.: 0.81-0.87).LncRNA possesses a significant diagnostic and prognostic ability for sepsis.

Osteosarcoma is a bone tumor that often affects children, adolescents and young people. Non-coding RNA activated by DNA damage (NORAD) can promote the proliferation of cancer cells in multiple tumors. Thus, the current study set out to explore the role of NORAD derived from extracellular vesicles (EVs) of bone mesenchymal stem cells (BMSCs) in osteosarcoma. First, NORAD was highly expressed in osteosarcoma cells and tissues, which might be associated with the progression and metastasis of osteosarcoma. We isolated EVs from the characterized BMSCs, and found that NORAD was transferred from BMSCs to osteosarcoma cells via EVs in the co-culture system. Consequently, NORAD delivered by BMSC-derived EVs promoted the proliferation and invasion of osteosarcoma cells. Subsequently, bioinformatics analyses suggested potential binding relationship between NORAD and microRNA-30c-5p (miR-30c-5p) as well as between miR-30c-5p and Krueppel-like factor 10 (KLF10), and the results of which were further verified by dual luciferase reporter gene assay, RNA immunoprecipitation, and RNA pull-down assay. Mechanistically, NORAD acted as a sponge of miR-30c-5p and up-regulated the expression of KLF10 where miR-30-c-5p mimic declined the effect induced by NORAD on cancer cells. The osteosarcoma cells were injected into mice to develop tumor growth and metastasis models. In these two models, injection of BMSC-EVs elevated NORAD expression and KLF10 but reduced miR-30c-5p expression, whereby suppressing tumor growth and lung metastasis. To conclude, BMSC-EVs deliver NORAD to osteosarcoma cells to regulate the miR-30c-5p/KLF10 axis, thereby accelerating the progression and metastasis of osteosarcoma.

Long non-coding RNAs (lncRNAs) are an emerging class of non-coding RNAs that do not encode proteins. These RNAs have various essential regulatory functions. Irregular expression of lncRNAs has been related to the pathological process of varied diseases, and are considered promising diagnostic biomarkers. LncRNAs can release into the circulation and be stable in body fluids as circulating lncRNAs. A subset of circulating lncRNAs that exist in exosomes are referred to as exosomal lncRNA molecules. These lncRNAs are highly stable and resist RNases. Exosomes have captured a great deal of attention due to their involvement in regulating communications between cells. In conditions of autoimmune disease, exosomes play critical roles in the pathological processes. In this context, circulating lncRNAs have been shown to modulate the immune response and indicated as prognosis and diagnostic biomarkers for autoimmune diseases. This review highlights the role of circulating lncRNAs (particularly exosomal) as diagnostic biomarkers for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, and Sjögren's syndrome.

Noncoding RNAs (ncRNAs) regulation of various diseases including cancer has been extensively studied. Reactive oxidative species (ROS) elevated by oxidative stress are associated with cancer progression and drug resistance, while autophagy serves as an ROS scavenger in cancer cells. However, the regulatory effects of ncRNAs on autophagy and ROS in various cancer cells remains complex. Here, we explore how currently investigated ncRNAs, mainly miRNAs and lncRNAs, are involved in ROS production through modulating antioxidant genes. The regulatory effects of miRNAs and lncRNAs on autophagy-related (ATG) proteins to control autophagy activity in cancer cells are discussed. Moreover, differential expression of ncRNAs in tumor and normal tissues of cancer patients are further analyzed using The Cancer Genome Atlas (TCGA) database. This review hypothesizes links between ATG genes- or antioxidant genes-modulated ncRNAs and ROS production, which might result in tumorigenesis, malignancy, and cancer recurrence. A better understanding of the regulation of ROS and autophagy by ncRNAs might advance the use of ncRNAs as diagnostic and prognostic markers as well as therapeutic targets in cancer therapy.

In this issue of the Biomedical Journal the reader is provided with an insight into the latest observations and advances in acute kidney injury as well as chronic kidney disease. The current SARS-CoV-2 variants are reviewed, and the role of long non-coding RNA in HIV therapy is explored. Furthermore, the potential of metabolomics as means to diagnose multiple sclerosis as well as tuberculosis is presented. Other topics of this issue include the restoration of the spermatogonial stem cell niche; atherosclerosis and the use of improved ultrasound images; and the effect of transcranial magnetic stimulation in patients with autism spectrum disorder. Finally, it is shown how continuous passive motion can be used as supportive therapeutic approach in children with cerebral palsy, and minimally invasive surgery is presented as valid alternative in cases of spine metastasis.

Background The abnormal expression of long non-coding RNA (lncRNA) Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) has been observed in many human cancers and the underlying mechanisms have been well studied. However, the function of OIP5-AS1 in acute kidney injury (AKI) remains unclear. Material and methods To explore the role of OIP5-AS1 in the progression of AKI, the cisplatin-induced AKI mouse and cell model were established. To confirm the potential protective effect of OIP5-AS1 during cisplatin-induced AKI, rescue experiments were performed. Targetscan was used to predict the potential targets of miR-144-5p. To further determine whether the effect of miR-144-5p during cisplatin-induced AKI was mediated by PMK2, the recuse experiments using PMK2 overexpressing vector was applied. Results OIP5-AS1 was significantly downregulated both in cisplatin-induced AKI mice and human renal tubular cell line HK-2 cells. Moreover, overexpression of OIP5-AS1 efficiently promoted cell growth and reduced cisplatin-induced apoptosis of HK-2 cells. Furthermore, OIP5-AS1 was identified as a sponge of miR-144-5p, and upregulation of miR-144-5p could significantly reverse overexpression of OIP5-AS1-induced protective effect on the damage of cisplatin to HK-2 cells. In addition, pyruvate kinase M2 (PKM2) was found to be a direct target of miR-144-5p, and overexpression of PKM2 efficiently reversed the effect of miR-144-5p mimics on the damage in cisplatin-stimulated HK-2 cells. Conclusions OIP5-AS1 reduced the apoptosis of cisplatin-stimulated renal epithelial cells by targeting the miR-144-5p/PKM2 axis, which extended the regulatory network of lncRNAs in cisplatin-induced AKI and also provided a novel therapeutic target for AKI treatment.

Long noncoding RNAs (lncRNAs) are RNA molecules involved in gene regulation at transcriptional, post-transcriptional, and epigenetic levels. LncRNAs participate in regulating apoptosis and autophagy in pancreatic cancer (PCa) and can promote and/or decrease the proliferation rate of tumor cells. The metastasis of PCa cells is tightly regulated by lncRNAs and they can affect the mechanism of epithelial-mesenchymal transition (EMT) to modulate metastasis. The drug resistance of PCa cells, especially to gemcitabine, can be affected by lncRNAs. In addition, lncRNAs enriched in exosomes can be transferred among tumor cells to regulate their proliferation and metastasis. Antitumor compounds, such as curcumin and ginsenosides, can regulate lncRNA expression in PCa therapy. As we discuss here, the expression level of lncRNAs can be considered as both a diagnostic and prognostic tool in patients with PCa.

Abstract A lot of long non-coding RNAs (lncRNAs) are expressed in human cells in a number of transcripts of different lengths and composition of exons. In case of cancer-associated lncRNAs, an actual task is to determine their specific isoforms, since each transcript can perform its own function in carcinogenesis and might have a unique expression profile in various types of tumors. For the first time, we analyzed the expression of CASC8 lncRNA in human pancreatic ductal adenocarcinoma cell lines and found an abundant isoform that was previously considered as the minor one in this type of cancer. We also revealed extremely high expression levels of all CASC8 transcripts in MIA PaCa-2 cells and, conversely, the lack of this lncRNA in PANC-1. This allows to use them as convenient models for further in vitro studies.

Various metabolic diseases are closely related to lipid metabolism disorders, but the regulatory effect of long noncoding RNAs (lncRNAs) on the function of lipids has been poorly elucidated. Previous our work has found that lncNONMMUG027912 (abbreviated as lnc027912) involved in cholesterol metabolism. Here, we further explored the novel function of lipid metabolism-associated lnc027912. We found that upregulated lnc027912 in AML12 cells treated with oleic acid (OA) and palmitic acid (PA) showed a significant decrease in lipid accumulation, triglyceride (TG) levels, and lipid biosynthesis genes. In terms of regulatory mechanisms, lnc027912 increased the expression of p-AMPKα, inhibited p-mTOR levels, decreased the expression of SREBP1C in nuclei, decreased the promoter activity of SREBP1C, and inhibited the expression of lipid synthesis genes. Most importantly, lnc027912 could reduce lipid accumulation and liver inflammation through AMPKα/mTOR signal axis in nonalcoholic fatty liver disease (NAFLD) mice model. Altogether, our study revealed a novel molecular mechanism of lnc027912 in lipid metabolism through the AMPKα/mTOR/SREBP1C signaling axis and highlights the potential of lnc027912 as a new treatment target for lipid disorder diseases (such as NAFLD).

Understanding of cancer with the help of ever-expanding cutting edge technological tools and bioinformatics is revolutionizing modern cancer research by broadening the space of discovery window of various genomic and epigenomic processes. Genomics data integrated with multi-omics layering have advanced cancer research. Uncovering such layers of genetic mutations/modifications, epigenetic regulation and their role in the complex pathophysiology of cancer progression could lead to novel therapeutic interventions. Although a plethora of literature is available in public domain defining the role of various tumor driver gene mutations, understanding of epigenetic regulation of cancer is still emerging. This review focuses on epigenetic regulation association with the pathogenesis of non-melanoma skin cancer (NMSC). NMSC has higher prevalence in Caucasian populations compared to other races. Due to lack of proper reporting to cancer registries, the incidence rates for NMSC worldwide cannot be accurately estimated. However, this is the most common neoplasm in humans, and millions of new cases per year are reported in the United States alone. In organ transplant recipients, the incidence of NMSC particularly of squamous cell carcinoma (SCC) is very high and these SCCs frequently become metastatic and lethal. Understanding of solar ultraviolet (UV) light-induced damage and impaired DNA repair process leading to DNA mutations and nuclear instability provide an insight into the pathogenesis of metastatic neoplasm. This review discusses the recent advances in the field of epigenetics of NMSCs. Particularly, the role of DNA methylation, histone hyperacetylation and non-coding RNA such as long-chain noncoding (lnc) RNAs, circular RNAs and miRNA in the disease progression are summarized.

As the most common malignant tumor, gliomas remain a poor prognosis while chemotherapy resistance is a medical problem for the treatment of glioma. Considering the correlation between drug resistance and ferroptosis, this study aims to explore the mechanism of chemotherapy resistance in glioma from the perspective of epigenetics. Because of the low expression of long non-coding RNA (lncRNA) ATXN8 opposite strand (ATXN8OS) in glioma cell lines, the role of ATXN8OS was explored by the detection on ferrous iron (Fe

We aimed to explore the function and competing endogenous RNA (ceRNA) pathway of MAFG-AS1 in breast cancer.qRT-PCR assay identified the expression of MAFG-AS1, miR-3612 and FKBP4. We used Western blot analysis to test the autophagy related protein levels in breast cancer cells. Functional assays such as Cell Counting Kit-8 (CCK8) assay, BrdU proliferation assay, Caspase-3 activity detection were used to identify the function of MAFG-AS1, miR-3612 and FKBP4 in breast cancer cells. Mechanism assays were used to verify the interacting relationship among MAFG-AS1, miR-3612 and FKBP4, including RNA pull down assay, RNA immunoprecipitation (RIP) assay and luciferase reporter assay.MAFG-AS1 and FKBP4 were both up-regulated in breast cancer tissues. MAFG-AS1 could function as an oncogene in breast cancer to activate cell proliferation, and inhibit cell apoptosis and autophagy. Meanwhile, MAFG-AS1 could sponge miR-3612 to elevate the expression of FKBP4. Besides, FKBP4 could activate the cell proliferation and inhibit cell apoptosis and autophagy, which could relieve the inhibitory effect of miR-3612 on breast cancer cells.MAFG-AS1 could activate breast cancer progression via modulating miR-3612/FKBP4 axis in vitro.

Pancreatic cancer is one of the most common causes of cancer death in the world due to the lack of early symptoms, metastasis occurrence and chemoresistance. Therefore, early diagnosis by detection of biomarkers, blockade of metastasis, and overcoming chemoresistance are the effective strategies to improve the survival of pancreatic cancer patients. Accumulating evidence has revealed that long noncoding RNA (lncRNA) and circular RNAs (circRNAs) play essential roles in modulating chemosensitivity in pancreatic cancer. In this review article, we will summarize the role of lncRNAs in drug resistance of pancreatic cancer cells, including HOTTIP, HOTAIR, PVT1, linc-ROR, GAS5, UCA1, DYNC2H1-4, MEG3, TUG1, HOST2, HCP5, SLC7A11-AS1 and CASC2. We also highlight the function of circRNAs, such as circHIPK3 and circ_0000284, in regulation of drug sensitivity of pancreatic cancer cells. Moreover, we describe a number of compounds, including curcumin, genistein, resveratrol, quercetin, and salinomycin, which may modulate the expression of lncRNAs and enhance chemosensitivity in pancreatic cancers. Therefore, targeting specific lncRNAs and cicrRNAs could contribute to reverse chemoresistance of pancreatic cancer cells. We hope this review might stimulate the studies of lncRNAs and cicrRNAs, and develop the new therapeutic strategy via modulating these noncoding RNAs to promote chemosensitivity of pancreatic cancer cells.

LncRNA ZNFX1 antisense RNA 1 (ZFAS1) could improve neuronal damage and inhibit inflammation and apoptosis. We conducted an in-depth exploration on the protective mechanism of ZFAS1 in cerebral ischemia-reperfusion injury. Overexpressed or silenced plasmids of ZFAS1 were transfected into the cells to analyze the effects of oxygen-glucose deprivation/reperfusion (OGD/R) treatment on the viability, apoptosis and related gene expressions of Neuro-2a cell by performing MTT assay, flow cytometry, qRT-PCR, and Western blot. Bioinformatic analysis, qRT-PCR, dual-luciferase reporter assay and RNA immunoprecipitation were used to screen and verify the miRNA(s) which could competitively bind with ZFAS1 and downstream mRNA(s) targeted by the miRNA(s). The effects of ZFAS1 and the above target miRNA(s) or gene(s) on the apoptosis of OGD/R-injured cells, apoptosis-related proteins, inflammatory factors and p65/IκBα pathway were further verified via the rescue test. The results from the middle cerebral artery occlusion (MCAO) mouse model

The purposes of this study are to explore the function and regulatory mechanism of a novel lncRNA MYC-Induced Long non-coding RNA (MINCR) in osteoarthritis (OA). The expression of lncRNA MINCR, miR-146a-5p, and bone morphogenetic protein receptor 2 (BMPR2), Sry-type high-mobility-group box 9 (SOX9), collagen type II alpha 1 (COL2A1), Aggrecan, metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), Matrix metalloproteinase 3 (MMP3), MMP13, COL2A1, and Aggrecan were determined using quantitative real-time PCR (qRT-PCR), western blot, immunohistochemistry (IHC) and immunofluorescence (IF)

Long non-coding RNAs (lncRNAs) are relevant to the development of human cancers. Here, we aimed to investigate the role and mechanism of Linc00883 in the proliferation, invasion, and migration of colorectal cancer (CRC) cells. CRC cell lines SW480 and LoVo were applied asiin vitro/imodels in this study. Quantitative real-time PCR was applied to measure Linc00883, miR-577, and FKBP14 expressions. Cell Counting Kit-8, transwell, and wound-healing assays were carried out to confirm the function of Linc00883. Western blot was applied to detect the protein levels of the epithelial-mesenchymal transition-related proteins E-cadherin, vimentin, fibronectin, and α-SMA. RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the relationship between Linc00883 and miR-577. Linc00883 expression was elevated in CRC tissues and cells, and the patients with high expression of Linc00883 were related to a low survival rate and prone to distant metastasis. Moreover, we corroborated that Linc00883 and miR-577, miR-577 and FKBP14 are bound to each other. Linc00883 was negatively correlated with miR-577, and miR-577 was also negatively correlated with FKBP14. Furthermore, interference with Linc00883 restrained the proliferation, invasion, and migration of CRC cells through the miR-577/FKBP14 axis.iIn vivo/istudies also clarified that Linc00883 facilitated the growth of CRC tumors and the epithelial-mesenchymal transition (EMT) of CRC. Our results demonstrated that Linc00883 facilitated the proliferation, invasion, and migration of CRC cells by regulating the miR-577/FKBP14 axis.

Breast carcinoma is one of the common causes of cancer-related mortality in women. Maternally expressed gene 3 (MEG3), a lncRNA located at 14q32, can be involved in carcinogenesis. In this study, we discovered that MEG3 was downregulated by CpG hypermethylation within its gene promoter. Functionally, treatment of breast cancer cells with the DNA methylation inhibitor 5-AzadC as well as silencing of DNA methyltransferase-1 (DNMT1) could decrease the abnormal hypermethylation of the MEG3 promoter, reverse MEG3 expression, inhibit cell proliferation and promote cell apoptosis. In addition, we found that MEG3 expression was negatively correlated with DNMT1. Mechanistically, MEG3 knockdown combined with 5-AzadC or sh-DNMT1 treatment restored the expression of Notch1 receptor, leading to the Notch1 pathway activation, and promoted the progression of epithelial mesenchymal transformation (EMT). Finally, the mice tumor model experiments showed that DNMT1 knockdown can increase MEG3 expression and inhibit tumor growth. Collectively, our findings uncovered that DNMT1-mediated MEG3 demethylation leads to MEG3 upregulation, which in turn inhibits the Notch1 pathway and EMT process in breast cancer.

DLEU2 has been proved to act as an oncogene in a variety of cancers, but its role in cardiovascular diseases is dearth of research. Thus, this study mainly discussed the effect and possible mechanism of DLEU2 on platelet-derived growth factor-BB (PDGF-BB)-triggered vascular smooth muscle cell (VSMC) injury. To obtain authentic results, the expressions of target genes in atherosclerosis serum were determined by reverse transcription quantitative PCR (RT-qPCR) and the protein levels were evaluated by Western blot. PDGF-BB was used to simply simulate the biological characteristics of VSMCs in vitro. The effect of DLEU2 on the biological behavior of PDGF-BB-induced VSMCs was analyzed by gain- and loss-of-function assays. Bioinformatics analysis, dual luciferase reporter assay, and Pearson correlation method were conducted to determine the relationship between target genes. The role of DLEU2/miR-212-5p/ YWHAZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta) axis in PDGF-BB-induced VSMCs was verified by rescue experiments. As a result, DLEU2 and YWHAZ were up-regulated, and miR-212-5p was down-regulated in atherosclerosis serum. Overexpressed DLEU2 facilitated the biological behavior of PDGF-BB-induced VSMCs, whilst siDLEU2 did the opposite. Moreover, overexpressed DLEU2 promoted proliferating cell nuclear antigen (PCNA) expression but repressed α-smooth muscle actin (α-SMA) and Calponin expressions, while it also enhanced YWHAZ expression via suppressing miR-212-5p. MiR-212-5p mimic and siYWHAZ reversed the effects of overexpressed DLEU2 on above biological characteristics and protein expressions in PDGF-BB-induced VSMCs, while the regulatory effect of miR-212-5p mimic was partially offset by overexpressed YWHAZ. Collectively, DLEU2 modulates PDGF-BB-induced VSMC injury via miR-212-5p/YWHAZ axis in atherosclerosis.

Lumbar disc herniation (LDH) is a common spinal disease that endangers human health. Genetic factors play a vital role in the progression of LDH. This study aimed to explore the relationship of the MIR31HG polymorphism with LDH risk in the Chinese population. Seven candidate SNPs on MIR31HG in 504 patients with LDH and 503 healthy people were genotyped by Agena MassARRAY platform. Logistic regression was used to calculate the relationship between MIR31HG polymorphism and LDH risk under different genetic models. Multi-factor dimensionality reduction (MDR) analysis was performed to evaluate the SNP–SNP interaction. We found that rs10965059 was significantly associated with a decreased risk of LDH under the dominant (OR = 0.46, 95% CI: 0.34–0.62, P 0.96, suggesting a significant linkage disequilibrium presence among each pair SNPs. MDR analysis showed that the best single-locus and multi-locus models for the prediction of LDH risk were rs10965059 and seven-locus models, respectively, and both of them increased LDH risk. Our results shown that in the Chinese Han population, the MIR31HG polymorphism rs10965059 was involved in a risk to symptomatic LDH, which provides a scientific basis for early screening, prevention, diagnosis and treatment of local LDH high-risk populations.

In vitro fertilization and embryo transfer (IVF-ET) is one of the effective methods to treat female infertility. Poor endometrial receptivity (ER) is an important factor leading to embryo implantation dysfunction, which can reduce pregnancy rate of IVF-ET. The mice model with embryo implantation dysfunction in vivo and attachment model of trophoblast (JAR) spheroids in vitro were constructed. The levels of lncRNA NEAT1, HOXA10, CTCF and markers of ER were detected. The cell proliferation was measured. The interaction between lncRNA NEAT1 and CTCF, HOXA10 promoter and CTCF were confirmed. LncRNA NEAT1 and HOXA10 levels in infertile patients and mice model with embryo implantation dysfunction were increased. In vitro experiments showed that down-regulation of lncRNA NEAT1 improved EECs proliferation and ER marker expressions. LncRNA NEAT1 could bind to CTCF, and CTCF could bind to HOXA10 promoter and down-regulate HOXA10 gene expression by regulating histone modification level. The lncRNA NEAT1/CTCF/HOXA10 signaling pathway regulated EECs proliferation and ER establishment in vitro and in vivo. Our study suggested that lncRNA NEAT1 could up-regulate HOXA10 promoter activity and its expression by combining with CTCF, thus improving EECs proliferation and ER establishment, and ultimately facilitating embryo implantation.

The HUGO Gene Nomenclature Committee (HGNC) is the sole group with the authority to approve symbols for human genes, including long non-coding RNA (lncRNA) genes. Use of approved symbols ensures that publications and biomedical databases are easily searchable and reduces the risks of confusion that can be caused by using the same symbol to refer to different genes or using many different symbols for the same gene. Here, we describe how the HGNC names lncRNA genes and review the nomenclature of the seven lncRNA genes most mentioned in the scientific literature.

Glioblastoma (GBM) is the most prevalent primary cerebral tumor in adults with high aggressiveness. Temozolomide (TMZ) is considered as the most widely used chemotherapy for GBM patients. Accumulating studies have proved that long non-coding RNAs (lncRNAs) participate in the pathogenesis of tumors. The aim of our study is to disclose the role of mir-99a-let-7c cluster host gene (MIR99AHG) in GBM. MIR99AHG expression was discovered to be elevated in GBM cells through quantitative real-time polymerase chain reaction (RT-qPCR) analysis. Loss-of-function experiments demonstrated that MIR99AHG silencing enhanced TMZ sensitivity of GBM both in vitro and in vivo. RNA pull down, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assays were implemented to unveil the underlying mechanism of MIR99AHG in GBM. The results of the mechanism assays implied that MIR99AHG interacted with microRNA-204-5p (miR-204-5p) and enhanced thioredoxin interacting protein (TXNIP) expression to inactivate the Nrf2/ARE signaling pathway. MIR99AHG/miR-204-5p/TXNIP regulatory axis was verified by rescue experiments in GBM. To summarize, MIR99AHG plays a promoting role in the TMZ resistance of GBM cells. The findings in this study might provide novel sight for the treatment for GBM.

Gouty arthritis (GA) is a type of self-limiting inflammatory arthritis caused by deposition of monosodium urate (MSU). This study aimed to analyze the expression variation of messenger RNAs (mRNAs) in GA patients and investigated the role of mRNAs in GA pathogenesis.Five patients with acute GA (AGA), 5 with non-acute GA (NAGA), and 5 healthy controls (HC) were recruited to examine differential mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) and explore whether mRNA is involved in the pathogenesis of AGA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to study the biological functions of differentially expressed mRNA and the relationship between genes and signal pathways.Compared with HC, the AGA group had 1456 differentially expressed mRNAs, while the NAGA group had 437 differentially expressed mRNAs and compared with the NAGA group, 115 differentially expressed mRNAs were found in the AGA group. GO analysis showed that the differentially expressed mRNA in the AGA group was mainly enriched in processes related to leukocyte activation and immune response, while KEGG analysis showed that "Staphylococcus aureus infection" and "Cytokine-cytokine receptor interaction" are enriched in the up-regulated mRNAs in the AGA group.This study identified genes and pathways that are differentially expressed during the onset of AGA, which might reveal part of the pathogenesis of the disease and provide clues to explaining the severe pain associated with disease onset and the rapid development of inflammatory response that subsides by itself.

Spinal cord injury (SCI) is known as a central nervous system disorder. Previous studies suggested that long-non-coding RNA RMRP (LncRNA RMRP) was abnormally expressed in SCI, but the potential underlying mechanism remains to be further explored. To explore the regulatory roles of LncRNA RMRP/miR-766-5p/FAM83A axis in SCI. Spinal T9 hemisection was performed on healthy adult male Sprague Dawley (SD) rats to establish the SCI rat models. The expressions of LncRNA RMRP in spinal cord of rats in different groups were examined by RT-qPCR. Moreover, AGE1.HN and PC12 cells were treated with hypoxic condition, and expression of LncRNA RMRP was examined by RT-qPCR methods. Furthermore, hypoxic PC12 cells were transfected with LncRNA RMRP OE, and the cell viability, proliferation, and apoptosis were examined. Next, the direct targeting relationship between LncRNA RMRP and miR-766-5p, as well as miR-766-5p and FAM83A, was confirmed by dual-luciferase reporter and RNA pull-down assays. Finally, the effects of LncRNA RMRP/miR-766-5p/FAM83A axis on cell viability, proliferation, and apoptosis were examined. LncRNA RMRP was downregulated in SCI rats and over-expression of LncRNA RMRP alleviated the SCI condition. LncRNA RMRP over-expression increased the viability and proliferation, and inhibited the apoptosis of hypoxic PC12 cells in vitro. miR-766-5p was confirmed as a target of LncRNA RMRP, and FAM83A was confirmed as a target of miR-766-5p. LncRNA RMRP could regulate the proliferation and apoptosis of hypoxic PC12 cells via regulating miR-766-5p/FAM83A axis in vitro. LncRNA RMRP may contribute to the pathogenesis of SCI via regulating miR-766-5p/FAM83A axis.

Osteosarcoma (OS) is the second most common primary malignant bone tumors in adolescents that causes cancer-related deaths. Previous studies have confirmed the promoting role of lncRNA HCP5 in the development of OS, but the specific mechanism is still not well understood. MiRNA levels were measured via RT-qPCR and protein expression was detected via western blotting. Cell proliferation was analyzed by CCK-8 assays and colony formations assay were conducted to measure colony formation ability. Dual-luciferase reporter assay was performed to detect the targeting relationship between HCP5 and miR-29b-3p, and between miR-29b-3p and LOXL2. Wound healing assays and Transwell assays were conducted to verify the migration and invasion abilities of OS cells. Correlations between the levels of HCP5 and miR-29b-3p, and between miR-29b-3p and LOXL2 were determined by Pearson correlation coefficient analysis. MiR-29b-3p expression was decreased and HCP5 and LOXL2 levels were increased in OS tissues and cell lines. MiR-29b-3p could directly act on LOXL2 and knockdown of LOXL2 restrained the proliferation, migration, and invasion of OS cells. Moreover, transfection with sh-HCP5-1 and sh-HCP5-2 suppressed the malignant biological behavior of OS cells. HCP5 directly targeted miR-29b-3p, and promoted OS proliferation, migration, and invasion via the miR-29b-3p/LOXL2 axis. The lncRNA HCP5 may upregulate LOXL2 expression by targeting miR-29b-3p, thereby promoting OS proliferation, migration, and invasion.

To study the clinical value of HEIH hyperexpression in gastric cancer and the molecular mechanism of promoting malignant proliferation of gastric cancer cells, qRT-PCR was used to detect the expression of HEIH in gastric cancer and nontumor gastric tissues. HEIH interference sequence was constructed to downregulate HEIH expression in MGC-803 and BGC-823 cell lines. CCK8, clonogenesis, and Transwell assay were used to detect the effects of HEIH on proliferation and invasion of tumor cells. The protein levels of STAT3, p-STAT3, P62, and LC3 were detected by Western blotting. The results showed that HEIH was highly expressed in gastric cancer ( P < 0.01 ). Interference of HEIH expression in MGC-803 and BGC-823 cells reduced the proliferation and invasion of gastric cancer cells, and the results were statistically significant ( P < 0.05 ). HEIH acts as a miRNA sponge for miR-4500. HEIH promotes gastric cancer development by inhibiting miR-4500. STAT3 is a downstream target of miR-4500. HEIH inhibits autophagy and promotes glycolysis. In conclusion, HEIH is highly expressed in gastric cancers. HEIH promotes malignant proliferation and development of gastric cancer cells. HEIH may be a new candidate site for pathological diagnosis and molecular drug therapy for future clinical treatment of gastric cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The aim of the present study was to explore the expression level of tumor protein 73 (TP73) in highly malignant CRC tumors and how the long non-coding RNA tumor protein 73 antisense RNA 1 (TP73-AS1) influences that transcription. We found that TP73-AS1 was highly expressed in malignant CRC samples in The Cancer Genome Atlas (TCGA) database. We also demonstrated TP73-AS1 was expressed in thirty samples of CRC tissues collected from China Medical University patients as well as in HCT116, RKO and SW480 CRC cell lines but not in HCoEpiC or CCD-18Co normal colon cells. Only wild-type TP73-AS1, but not any of its alternate splicing isoforms, was positively correlated with tumor malignancy. TP73-AS1 transcripts were shown to be located in cell nuclei especially in close proximity to the TP73 promoter in CRC cells, but not in normal colon cells. In addition, an interaction between lysine demethylase 5A (KDM5A) and TP73-AS1 in CRC cells, but not normal colon cells, and KDM5A localization on the TP73 promoter were influenced by TP73-AS1. Interestingly, the H3K4me3 level on the TP73 promoter was reduced, but was elevated by TP73-AS1 knockdown in CRC cells. In conclusion, these results suggest a novel epigenetic role of TP73-AS1 on histone demethylation that influences TP73 transcription, and shed light on malignancy in CRC.

Cervical cancer is one of the most frequent types of cancer in women, which is characterized by high invasion and metastatic tendency in its advanced stage. Emerging evidence indicated that long non-coding RNAs (LncRNAs) are involved in the pathogenesis of cervical cancer. LINC01287 has been reported to play crucial regulatory roles in the pathogenesis and progression of multiple cancers. However, up until now, whether LINC01287 is associated with the initiation and development of cervical cancer remains largely unknown. In the present study, expression levels of LINC01287, miR-513a-5p and stress-associated endoplasmic reticulum protein 1 (SERP1) mRNA were quantified utilizing qRT-PCR. A series of functional experiments including CCK-8 assay, colony formation assay, transwell assay, flow cytometry, and tumor xenograft growth of cervical cancer cells were performed for studying the effects of LINC01287. The luciferase reporter assay, pull-down assay, and western blot were used to confirm the downstream targets of LINC01287 and miR-513a-5p. The results demonstrate that LINC01287 was highly expressed in cervical cancer tissue samples and cell lines. High LINC01287 predicts a poor prognosis for cervical cancer patients. Additional gain- and loss-of-function experiments demonstrated that silencing LINC01287 inhibited cervical cancer cells proliferation, colony formation, migration, apoptosis in vitro and retarded tumor growth and metastasis in vivo. Furthermore, the dual-luciferase reporter gene system and RNA pulldown assay validated that LINC01287 positively regulated SERP1 expressions by sponging miR-513a-5p, and LINC01287 inhibited cervical cancer progression by regulating miR-513a-5p/SERP1 axis. In conclusion, the current study first identified that LINC01287/miR-513a-5p/SERP1 axis played an important role in cervical cancer progression. LINC01287 might be a prognostic biomarker and a target for new therapies in patients with cervical cancer.

Aim: More patients are resuscitated from cardiac arrest and cardiopulmonary resuscitation (CA/CPR) due to advances in medical care. However, the burden now lies with post-cardiac arrest cognitive impairment in CA/CPR survivors. Based on our previous study, we aimed to further confirm the correlation between the long noncoding RNA-promoting ShcA (lncRNA-PS)/Src homology and collagen A (ShcA) axis and CA/CPR-induced cognitive impairment in molecular, cellular, and tissue levels. Methods and Results: The in vivo experiments were based on a mouse model of CA/CPR, while oxygen-glucose deprivation and reoxygenation was used as a cell model in vitro. Conditional ShcA suppression in neurons of the hippocampal CA1 region was achieved by cyclization recombinase of bacteriophage P1 recognizing DNA fragment locus of x-over P1 site (Cre/LoxP recombination system). Genetic manipulation of HT22 was achieved by lentivirus targeting lncRNA-PS and ShcA. Neurological function score was remarkably decreased, and cognitive function was affected after restoration of spontaneous circulation. LncRNA-PS and ShcA overexpression after CA/CPR, mainly happened in neurons of hippocampal CA1 region, was observed by in situ hybridization and immunofluorescence. Neuronal ShcA knockdown in hippocampal CA1 region before CA/CPR attenuated cognitive impairment after CA/CPR. ShcA deficiency protected HT22 cell line against oxygen-glucose deprivation and reoxygenation by inhibiting inflammation and apoptosis. In vitro upregulation of lncRNA-PS elevated ShcA expression, which was reversed by knockdown of ShcA. Conclusions: This study revealed that lncRNA-PS/ShcA axis is critically involved in the pathogenesis of cognitive impairment after CA/CPR. By inhibiting ShcA expression in neurons of the hippocampal CA1 region could improve the survival outcomes in mice after CA/CPR.

Backgrounds. Long noncoding RNAs (lncRNAs) are strongly associated with the development of breast cancer (BC). As yet, the function of LINC01234 in BC remains unknown. Methods. Using biological information, the potential lncRNA, miRNA, and target gene were predicted. LINC01234 and miR-525-5p expression in BC tissues was detected using quantitative real-time reverse transcription polymerase chain reaction. Fluorescence in situ hybridization was used to determine the distribution of LINC01234. Cell proliferation was analyzed using CCK-8 assay, colony formation, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and apoptosis evaluated using flow cytometry. Western blotting was used to evaluate protein expression. Dual-luciferase® reporter, RNA pull-down, and RNA immunoprecipitation assays were performed to analyze the binding relationships among LINC01234, miR-525-5p, and cold shock domain-containing E1 (CSDE1). Results. We screened out LINC01234, found to be significantly increased in BC tissues, associated with a poor prognosis, and positively correlated with tumor size of BC. Knockdown of LINC01234 suppressed BC cell growth and facilitated apoptosis. Dual-luciferase reporter®, RNA pull-down, and RNA immunoprecipitation assays confirmed that LINC01234 and CSDE1 directly interacted with miR-525-5p. Upregulation of miR-525-5p and suppression of CSDE1 inhibited BC cell growth and induced cell apoptosis. Conclusion. Upregulation of LINC01234 contributes to the development of BC through the miR-525-5p/CSDE1 axis. LINC01234 may be one of the potential diagnostic and treatment targets for BC.

Hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) is a common, highly invasive malignant tumor associated with a high mortality rate. This study aimed to identify the effective diagnostic and prognostic biomarkers for HBV-related HCC. With HBV-related HCC RNA-sequencing data of The Cancer Genome Atlas (TCGA) database, 159 differentially expressed long noncoding RNAs (lncRNAs) between HBV-related HCC and para-carcinoma normal samples were identified, and 12 lncRNAs were eventually assessed for deeper research. Classification analysis developed a three-lncRNA signature of AC005332.5, ELF3-AS1 and LINC00665, which was demonstrated to be the most discriminatory with an AUC (Area under the curve) value of 0.913 (95% CI: 0.8610-0.9665) and verified in validation patients. The expression levels of AC005332.5, ELF3-AS1 and LINC00665 were significantly changed with different tumor stages or grades. Survival analysis revealed that AC005332.5, ELF3-AS1 and LINC00665 were highly associated with the prognosis of overall survival. Additionally, the lncRNA signature yielded statistical significance to predict clinical outcomes independently from other clinical variables in validation patients, as suggested in the multivariate Cox hazards analysis. Conclusively, a three-lncRNA signature of AC005332.5, ELF3-AS1 and LINC00665 may serve as an excellent diagnostic biomarker for HBV-related HCC and potential prognostic significance for HBV-related HCC sufferers.

Noncoding RNA (ncRNA) is a kind of RNA that plays a key role in a variety of biological processes, illnesses, and tumours despite the fact that it cannot be translated into proteins. The HT29 colon cancer cell line was utilized to create a 5-FU drug-resistant cell strain (control group), a lentivirus SNHG20 carrier (OE-SNHG20 group), and an SNHG20 shRNA carrier (SNHG20 shRNA carrier group) (SE-SNHG20 group). To determine the expression of cell SNHG20, a real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was utilized, and cholecystokinin-octapeptide (CCK-8) was used to detect the difference in 5-FU inhibitory concentration 50. The goal of the study was to see how variations in long nonencoding ribonucleic acid (lncRNA) SNHG20 expression affect colon cancer cell 5-fluorouracil (5-FU) chemotherapeutic sensitivity by collecting colon cancer and normal para cancer tissues and analysing the differences in SNHG20 expression. The ability of cell cladogenesis was tested using platform cladogenesis. Cell apoptosis was detected using flow cytometry. Western blots revealed the presence of protein phosphatidylinositol kinase (PI3K), protein kinase B (AKT), caspase-3, e-cadherin, and matrix metalloproteinase 9 (MMP-9) enzymes. The findings revealed that SNHG20 expression was considerably upregulated ( P < 0.05 ) in colon cancer tissue and 5-FU drug-resistant colon cancer cells. Cell 5-FU IC50, cell cladogenesis, cell survival rate, and MMP-9, P-PI3K, and P-AKT expression were all significantly improved. Cell apoptosis and expressions of E-cadherin and caspase-3, on the other hand, were considerably decreased ( P < 0.05 ). Cell 5-FU IC50, cell cladogenesis, cell survival rate, and the expressions of MMP-9, P-PI3K, and P-AKT were all significantly lower in the SE-SNHG20 group, although cell apoptosis and the expressions of E-cadherin and caspase-3 were significantly higher ( P < 0.05 ). The results revealed that lncRNA SNHG20 could inhibit the chemotherapeutic sensitivity of colon cancer cells to 5-FU by regulating PI3K/AKT pathways. The inhibition of lncRNA SNHG20 expression could promote the apoptosis and proliferation of 5-FU-resistant colon cancer cells.

The measurement of long noncoding RNAs (lncRNAs) is essential to diagnosis and treatment of various diseases such as cancers. Herein, we develop a simple method to simultaneously detect multiple lncRNAs using programmable ligation-transcription circuit-driven cascade amplification and single-molecule counting. The presence of targets lncRNA HOTAIR and lncRNA MALAT1 activates the ligation-transcription circuits to produce two corresponding functional RNAs. The functional RNAs then cyclically initiate the digestion of signal probes by duplex-specific nuclease to liberate Cy5 and Cy3 molecules. After magnetic separation, the liberated Cy5 and Cy3 molecules are measured by single-molecule counting. In this assay, a single lncRNA can activate ligation-transcription circuit to generate abundant functional RNAs, endowing this assay with high sensitivity. Integration of single-molecule counting ensures the high sensitivity. This method shows extremely high sensitivity with a limit of detection (LOD) of 0.043 aM for HOX gene antisense intergenic RNA (lncRNA HOTAIR) and 0.126 aM for mammalian metastasis-related lung adenocarcinoma transcript 1 (lncRNA MALAT1). Importantly, this method enables simultaneous measurement of multiple endogenous lncRNAs at the single-cell level, and it may discriminate the expressions of various lncRNA in lung tumor tissues of nonsmall cell lung cancer (NSCLC) patients and their corresponding healthy adjacent tissues, offering a promising platform for clinical diagnosis and biomedical research.

Increasing evidence has shown that long non-coding RNAs (lncRNAs), which are non-coding endogenous single-stranded RNAs, play an essential role in various physiological and pathological processes through transcriptional interference, post-transcriptional regulation, and epigenetic modification. Moreover, lncRNAs, as oncogenes or tumor suppressor genes, play an important role in the occurrence and development of human cancers. Prostate androgen-regulated transcript 1 (PART1) was initially identified as a carcinogenic lncRNA in prostate adenomas. The upregulated expression of PART1 plays a tumor-promoting role in liver, prostate, lung cancers, and other tumors. In contrast, the expression of PART1 is downregulated in esophageal squamous cell carcinoma, glioma, and other tumors, which may inhibit the tumor. PART1 plays a dual role in cancer and regulates cell proliferation, apoptosis, invasion, and metastasis through a variety of potential mechanisms. These findings suggest that PART1 is a promising tumor biomarker and therapeutic target. This article reviews the biological functions, related mechanisms, and potential clinical significance of PART1 in a variety of human cancers.

Motivation The advancement of high-throughput technology characterizes a wide variety of epigenetic modifications and noncoding RNAs across the genome involved in disease pathogenesis via regulating gene expression. The high dimensionality of both epigenetic/noncoding RNA and gene expression data make it challenging to identify the important regulators of genes. Conducting univariate test for each possible regulator–gene pair is subject to serious multiple comparison burden, and direct application of regularization methods to select regulator–gene pairs is computationally infeasible. Applying fast screening to reduce dimension first before regularization is more efficient and stable than applying regularization methods alone. Results We propose a novel screening method based on robust partial correlation to detect epigenetic and noncoding RNA regulators of gene expression over the whole genome, a problem that includes both high-dimensional predictors and high-dimensional responses. Compared to existing screening methods, our method is conceptually innovative that it reduces the dimension of both predictor and response, and screens at both node (regulators or genes) and edge (regulator–gene pairs) levels. We develop data-driven procedures to determine the conditional sets and the optimal screening threshold, and implement a fast iterative algorithm. Simulations and applications to long noncoding RNA and microRNA regulation in Kidney cancer and DNA methylation regulation in Glioblastoma Multiforme illustrate the validity and advantage of our method. Availability and implementation The R package, related source codes and real datasets used in this article are provided at https://github.com/kehongjie/rPCor. Supplementary information Supplementary data are available at Bioinformatics online.

Background: Molecular subtyping of bladder cancer has revealed luminal tumors generally have a more favourable prognosis. However, some aggressive forms of variant histology, including micropapillary, are often classified luminal. In previous work, we found long non-coding RNA (lncRNA) expression profiles could identify a subgroup of luminal bladder tumors with less aggressive biology and better outcomes. Objective: In the present study, we aimed to investigate whether lncRNA expression profiles could identify high-grade T1 micropapillary bladder cancer with differential outcome. Design, setting, and participants: LncRNAs were quantified from RNA-seq data from a HGT1 bladder cancer cohort that was enriched for primary micropapillary cases (15/84). Unsupervised consensus clustering of variant lncRNAs identified a three-cluster solution, which was further characterised using a panel of micropapillary-associated biomarkers, molecular subtypes, gene signatures, and survival analysis. A single-sample genomic signature was trained using lasso-penalized logistic regression to classify micropapillary-like gene-expression, as characterised by lncRNA clustering. The genomic classifier (GC) was tested on luminal tumors derived from the TCGA cohort (N = 202). Outcome measurements and statistical analysis: Patient and tumor characteristics were compared between subgroups by using X2 tests and two-sided Wilcoxon rank-sum tests. Primary endpoints were overall, progression-free and high-grade recurrence-free survival, calculated as the date of high-grade T1 disease at TURBT till date of death from any cause, progression, or recurrence, respectively. Survival rates were estimated using weighted Kaplan–Meier (KM) curves. Results and limitations: Primary micropapillary HGT1 showed decreased FGFR3, SHH, and p53 pathway activity relative to tumors with conventional urothelial carcinoma. Many bladder cancer-associated lncRNAs were downregulated in micropapillary tumors, including UCA1, LINC00152, and MALAT1. Unsupervised consensus clustering resulted in a lncRNA cluster 1 (LC1) with worse prognosis that was enriched for primary micropapillary histology and the Luminal Unstable (LumU) molecular subtype. Interestingly, LC1 appeared to better identify aggressive HGT1 disease, compared to stratifying outcomes using primary histologic characteristics. A signature trained to identify LC1 cases showed good performance in the testing cohort, identifying seven cases with significantly worse survival (p < 0.001). Limitations include the retrospective nature of the study and the lack of a validation cohort. Conclusions: Using the lncRNA transcriptome we identified a subgroup of aggressive HGT1 bladder cancer that was enriched with micropapillary histology. These data suggest that lncRNAs can facilitate the identification of aggressive micropapillary-like tumors, potentially improving patient management.

T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy caused by clonal proliferation of T-cell pre-cursors arising from the thymus. Although the optimized chemotherapy regimen could improve the outcome of such patients, some challenges such as higher risk for induction failure, early relapse and isolated central nervous system (CNS) relapse occurring in T-ALL patients are of great significance, leading to increased mortality rates. Long non-coding RNA (lncRNA) is a key component involved in cell signaling through a variety of mechanisms in regulating gene expression. Oncogenes and tumor suppressors are no exception and their expression can be affected by lncRNAs. In addition, accumulating researches in samples from T-ALL patients as well as pre-clinical studies in mice suggest that the expression profile of lncRNAs in T-ALL could be aberrant, resulting in deregulation of target genes and downstream signaling pathways. In addition, accumulating researches in samples from T-ALL patients as well as pre-clinical studies in mice suggest that the expression profile of lncRNAs in T-ALL could be aberrant, resulting in deregulation of target genes and downstream signaling pathways. These lncRNAs may be determinants of proliferation, apoptosis, and drug resistance observed in T-ALL. Thus, lncRNAs can be a good tool to develop novel strategies against cancer cells in the treatment of relapsed and refractory T-ALL. They can also act as promoting biomarkers in assessing T-ALL and differentiating between patients with poor prognosis and good prognosis.

Long non-coding RNAs (LncRNA) play important roles in multiple types of cancers. We addressed the role of LINC02535 by regulating the miR-30a-5p /GalNAc Transferase 3 (GALNT3) axis to promote the proliferation, migration, and invasion in lung adenocarcinoma (LUAD) cells. The Cancer Genome Atlas (TCGA) database screened differentially expressed lncRNAs. Quantitative real-time PCR analysis (qRT-PCR) confirmed that LINC02535 is highly expressed in LUAD tissues and cells.

Glioblastoma (GBM) is the most malignant form of brain cancer in the world. Nevertheless, the survival rate of patients with GBM is extremely low. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) conduct important biological functions in patients' survival status and the immunotherapeutic response. Here, m6A-related lncRNAs were identified by a co-expression method. Univariate and multivariate Cox regression together with LASSO were applied to establish the risk model. Kaplan-Meier and ROC analysis were applied to evaluate the prediction power of this risk model. Finally, the related immune profiling and chemical sensitivity targets were also investigated. The risk model holding three m6A-related lncRNAs was confirmed as an independent predictor for the prognosis. Furthermore, we found the risk model based on m6A-related lncRNAs is associated with the immune status, immunosuppressive biomarkers, and chemo-sensitivity in GBM patients. The RP11-552D4.1 is found to facilitate neuronal proliferation. This risk model consisted of m6A-related lncRNAs may be available for the clinical interventions in GBM patients.

Sustaining DNA damage response (DDR) signalling via retention of DDR factors at damaged sites is important for transmitting damage-sensing and repair signals. Herein, we found that DNA damage provoked the association of ribosomes with IRES region in lncRNA CTBP1-DT, which overcame the negative effect of upstream open reading frames (uORFs), and elicited the novel microprotein DNA damage-upregulated protein (DDUP) translation via a cap-independent translation mechanism. Activated ATR kinase-mediated phosphorylation of DDUP induced a drastic ‘dense-to-loose’ conformational change, which sustained the RAD18/RAD51C and RAD18/PCNA complex at damaged sites and initiated RAD51C-mediated homologous recombination and PCNA-mediated post-replication repair mechanisms. Importantly, treatment with ATR inhibitor abolished the effect of DDUP on chromatin retention of RAD51C and PCNA, thereby leading to hypersensitivity of cancer cells to DNA-damaging chemotherapeutics. Taken together, our results uncover a plausible mechanism underlying the DDR sustaining and might represent an attractive therapeutic strategy in improvement of DNA damage-based anticancer therapies.

Sno-lncRNAs are intron-derived long noncoding RNAs (lncRNAs) with snoRNA ends. Sno-lncRNAs were first discovered in the human Prader-Willi (PWS)/Angelman (AS) imprinted domain. Here, we report the identification and characterization of four sno-lncRNA types (sno-lncRNA1, sno-lncRNA2, sno-lncRNA3, and sno-lncRNA4) in the bovine PWS/AS imprinted domain. Reverse transcription-PCR first determined the cDNA sequences of the four bovine sno-lncRNAs. A gene structure analysis showed that sno-lncRNA1 lacks introns, but sno-lncRNA2 and sno-lncRNA3 have one and two introns respectively. The three sno-lncRNAs have similar snoRNA ends. Moreover, the three have similar snoRNAs at their 5' and 3' ends. The head-to-tail orientation has six sno-lncRNA copies arranged between bovine SNORD116-6 and SNORD116-12. Moreover, only a copy of sno-lncRNA4 was located between SNORD116-3 and SNORD116-4. The expression of the four sno-lncRNAs was analyzed in the bovine heart, liver, spleen, lung, kidney, muscle, fat, brain, and placenta tissues. The monoallelic expression of sno-lncRNA4 was determined in bovine tissues. The results showed that the four sno-lncRNAs are widely expressed in the nine tissues, although sno-lncRNA3 and sno-lncRNA4 were undetected in the placenta. Moreover, an informative single nucleotide polymorphism (rs448706424) revealed the allelic expression of sno-lncRNA4 in exon 2 of sno-lncRNA4. The bovine genome had six copies of sno-lncRNA1, sno-lncRNA2, and sno-lncRNA3, but their allelic expression was not identified.

Esophageal squamous cell carcinoma (ESCC) is the most prevalent form of esophageal cancer in China and is closely associated with malignant biological characteristics and poor survival. Ferroptosis is a newly discovered iron-dependent mode of cell death that plays an important role in the biological behavior of ESCC cells. The clinical significance of ferroptosis-related long noncoding RNAs (FRLs) in ESCC remains unknown and warrants further research. The current study obtained RNA sequencing profiles and corresponding clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and FRLs were obtained through coexpression analysis. Consensus clustering was employed to divide the subjects into clusters, and immune-associated pathways were identified by functional analysis. The current study observed significant differences in the enrichment scores of immune cells among different clusters. Patients from TCGA-ESCC database were designated as the training cohort. A ten-FRL prediction signature was established using the least absolute shrinkage and selection operator Cox regression model and validated using the GEO cohort and our own independent validation database. Real-time quantitative polymerase chain reaction was used to verify the expression of the ten FRLs, and the ssGSEA analysis was employed to evaluate their function. In addition, the IMvigor database was used to assess the predictive value of the signature in terms of immunotherapeutic responses. Multivariate Cox and stratification analyses revealed that the ten-FRL signature was an independent predictor of the overall survival (OS). Patients with ESCC in the high-risk group displayed worse survival, a characteristic tumor immune microenvironment, and low immunotherapeutic benefits compared to those in the low-risk group. Collectively, the risk model established in this study could serve as a promising predictor of prognosis and immunotherapeutic response in patients with ESCC.

Development of colon adenocarcinoma (COAD) metastasis involves several mediators including fluid shear stress (FSS), intracellular ROS levels, and non-coding RNAs. In our present study, we identified and investigated the role of regulatory non-coding RNA molecules specifically involved in COAD metastasis and their association with FSS and ROS. Interactions between the mRNAs associated with FSS and ROS, the corresponding microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in COAD metastasis were used to generate the mRNA-miRNA-lncRNA-circRNA network. Experimental validation of the identified RNA hubs using quantitative real-time PCR demonstrated a direct effect of the FSS on their expression levels in cancer cells. FSS resulted in the downregulation of HMGA1 and RAN, as well as the upregulation of HSP90AA1, PMAIP1 and BIRC5. Application of shear stress also led to downregulation of hsa-miR-26b-5p and hsa-miR-34a-5p levels in HCT116 cells. Further, functional enrichment and survival analysis of the significant miRNAs, as well as the OncoPrint and the survival analyses of the selected mRNAs were performed. Subsequently, their functional role was also corroborated with existing literature. Ten significant miRNA hubs were identified, out of which hsa-miR-17-5p and hsa-miR-20a-5p were found to interact with lncRNA (CCAT2) while hsa-miR-335 was found to interact with four circRNAs. Fifteen significant miRNAs were identified in 10 different modules suggesting their importance in FSS and ROS-mediated COAD metastasis. Finally, 10 miRNAs and 3 mRNAs associated with FSS and/or ROS were identified as significant overall survival markers; 33 mRNAs were also identified as metastasis-free survival markers whereas 15 mRNAs showed 10% gene alterations in TCGA-COAD data and may serve as promising therapeutic biomarkers in the COAD metastasis.

Somatic copy-number alterations (CNA) promote cancer, but the underlying driver genes may not be comprehensively identified if only the functions of the encoded proteins are considered. mRNAs can act as competitive endogenous RNAs (ceRNA), which sponge miRNAs to posttranscriptionally regulate gene expression in a protein coding–independent manner. We investigated the contribution of ceRNAs to the oncogenic effects of CNAs. Chromosome 1q gains promoted melanoma progression and metastasis at least in part through overexpression of three mRNAs with ceRNA activity: CEP170, NUCKS1, and ZC3H11A. These ceRNAs enhanced melanoma metastasis by sequestering tumor suppressor miRNAs. Orthogonal genetic assays with miRNA inhibitors and target site blockers, along with rescue experiments, demonstrated that miRNA sequestration is critical for the oncogenic effects of CEP170, NUCKS1, and ZC3H11A mRNAs. Furthermore, chromosome 1q ceRNA-mediated miRNA sequestration alleviated the repression of several prometastatic target genes. This regulatory RNA network was evident in other cancer types, suggesting chromosome 1q ceRNA deregulation as a common driver of cancer progression. Taken together, this work demonstrates that ceRNAs mediate the oncogenicity of somatic CNAs. Significance: The function of CEP170, NUCKS1, and ZC3H11A mRNAs as competitive endogenous RNAs that sequester tumor suppressor microRNAs underlies the oncogenic activity of chromosome 1q gains.

Recent studies suggest noncoding RNAs interact with genomic DNA, forming RNA•DNA-DNA triple helices, as a mechanism to regulate transcription. One way cells could regulate the formation of these triple helices is through RNA modifications. With over 140 naturally occurring RNA modifications, we hypothesize that some modifications stabilize RNA•DNA-DNA triple helices while others destabilize them. Here, we focus on a pyrimidine-motif triple helix composed of canonical U•A-T and C•G-C base triples. We employed electrophoretic mobility shift assays and microscale thermophoresis to examine how 11 different RNA modifications at a single position in an RNA•DNA-DNA triple helix affect stability: 5-methylcytidine (m5C), 5-methyluridine (m5U or rT), 3-methyluridine (m3U), pseudouridine (Ψ), 4-thiouridine (s4U), N6-methyladenosine (m6A), inosine (I), and each nucleobase with 2′-O-methylation (Nm). Compared to the unmodified U•A-T base triple, some modifications have no significant change in stability (Um•A-T), some have ∼2.5-fold decreases in stability (m5U•A-T, Ψ•A-T, and s4U•A-T), and some completely disrupt triple helix formation (m3U•A-T). To identify potential biological examples of RNA•DNA-DNA triple helices controlled by an RNA modification, we searched RMVar, a database for RNA modifications mapped at single-nucleotide resolution, for lncRNAs containing an RNA modification within a pyrimidine-rich sequence. Using electrophoretic mobility shift assays, the binding of DNA-DNA to a 22-mer segment of human lncRNA Al157886.1 was destabilized by ∼1.7-fold with the substitution of m5C at known m5C sites. Therefore, the formation and stability of cellular RNA•DNA-DNA triple helices could be influenced by RNA modifications.

Colon cancer is one of the most prevalent malignant tumors across the world. Increasing studies have demonstrated that long non-coding RNAs (lncRNAs) take part in colon cancer development. Our study intends to explore the expression characteristics of LBX2-AS1, a novel lncRNA, in colon cancer and its underlying mechanisms. The results illustrated that LBX2-AS1 level was substantially increased in colon cancer tissues and was obviously correlated with the tumor volume and early distant metastasis of patients. Besides, overexpression of LBX2-AS1 remarkably boosted growth, proliferation, and metastasis and restrained apoptosis in colon cancer cells, whereas LBX2-AS1 knockdown produced the opposite effect. On the other hand, miR-627-5p, down-regulated in colon cancer tissues, was negatively associated with LBX2-AS1 expression. Functional experiments showed that miR-627-5p suppressed colon cancer growth. Mechanistically, LBX2-AS1, as an endogenous competitive RNA, targeted miR-627-5p and restrained its expression, while miR-627-5p targeted and negatively regulated the RAC1/PI3K/AKT axis. Collectively, this study has revealed that LBX2-AS1 is a poor prognostic factor of colon cancer and can regulate colon cancer progression by regulating the miR-627-5p/RAC1/PI3K/AKT pathway.

Being one of the most lethal malignant tumors worldwide, pancreatic carcinoma (PC) shows strong invasiveness and high mortality. In tumorigenesis and progression, the role played by long-chain noncoding RNAs (lncRNAs) cannot be ignored. This article mainly probes into the function of lncRNA ZFAS1 in PC. ZFAS1 expression in PC and normal counterparts retrieved from the Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA) database was analysed by GEPIA2. Its expression profile in clinical specimens and human PC cell strains was quantified using qRT-PCR. Measurements of BxPC-3 cell multiplication and invasiveness employed CCK-8, plate clone formation test, and Transwell chamber assay. ZFAS1’s impact on lipid content in BxPC-3 cells was detected. RNA pulldown and RIP assays analyzed the interaction of ZFAS1 with U2AF2 and HMGCR in BxPC-3 cells. Finally, the impacts of U2AF2 and HMGCR on the biological behavior of BxPC-3 were observed. ZFAS1 was kept at a high level in PC tissues versus the normal counterparts. ZFAS1 gene knockout remarkably suppressed PC cell multiplication and invasiveness and decreased the contents of free fatty acids, total cholesterol, triglycerides, and phospholipids. Mechanistically, ZFAS1 stabilized HMGCR mRNA through U2AF2, thus increasing HMGCR expression and promoting PC lipid accumulation. Meanwhile, reduced PC cell viability and invasiveness were observed after downregulating U2AF2 and HMGCR. As an oncogene of PC, ZFAS1 can modulate lipometabolism and stabilize HMGCR mRNA expression by binding with U2AF2 in PC, which is a candidate target for PC diagnosis and treatment.