Graphene oxide accelerates diabetic wound repair by inhibiting apoptosis of Ad-MSCs via Linc00324/miR-7977/STK4 pathway.

Many studies have shown that graphene oxide (GO) promotes proliferation and differentiation of a variety of stem cells. However, its effect on adipose-derived mesenchymal stem cell (Ad-MSCs) apoptosis is still unclear. Apoptosis is a significant factor affecting stem cell-based treatment of diabetic wounds. Therefore, we explored the effect of GO on Ad-MSC apoptosis and diabetic wound healing. In this study, qRT-PCR was used to detect Ad-MSC expression of LncRNAs, miRNAs, and mRNAs under high-glucose environment. RNA immunoprecipitation (RIP), RNA pull-down, and luciferase assays were used to detect interactions of specific lncRNAs, miRNAs, and mRNAs. The effects of GO on Ad-MSC apoptosis were explored by flow cytometry, TUNEL assay, and Western blot. A diabetic wound model was used to explore the function of Linc00324 on Ad-MSC reparative properties in vivo. As a result, GO inhibited high glucose-induced apoptosis in Ad-MSCs, and Linc00324 contributed to the anti-apoptotic effect of GO. RIP and RNA pull-down confirmed that Linc00324 directly interacted with miR-7977, functioning as a miRNA sponge to regulate expression of the miR-7977 target gene STK4 (MST1) and downstream signaling pathways. In addition, GO reduced the apoptosis of Ad-MSCs in wounds and promoted wound healing. Taken together, these findings suggest GO may be a superior auxiliary material for Ad-MSCs to facilitate diabetic wound healing via the Linc00324/miR-7977/STK4 pathway.

Comprehensive analysis of lncRNA expression profiles in rats with cerebral ischemia-reperfusion injury after treatment with 20(R)-ginsenoside Rg3.

This study was aimed at investigating the differentially expressions of long noncoding RNAs (lncRNAs) and mRNAs in the brains of a middle cerebral artery occlusion/reperfusion (MCAO/R) group and a MCAO/R + 20(R)-Rg3 group. Biological enrichment analysis was performed, and a lncRNA-mRNA coexpression network was constructed, to reveal the targets and pathways of 20(R)-Rg3 involved in the regulation of cerebral ischemia-reperfusion injury (CIRI). The RNA-seq high-throughput sequencing method was employed to detect differentially-expressed genes between the groups, which were verified by RT-PCR. Functional enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to explore the biological functions and relevant pathways. The coexpression network of the screened lncRNAs and mRNAs was built by using Cytoscape software. The results identified 77 upregulated lncRNAs, 162 downregulated lncRNAs, 66 upregulated mRNAs and 472 downregulated mRNAs in the MCAO/R + 20(R)-Rg3 group, compared with those in the MCAO/R group. GO enrichment analysis showed that the GO terms were mainly enriched in stimulation response, cellular response, and stress response. KEGG pathways were mainly related to the tumor necrosis factor (TNF), NF-κB, cytokine, and other receptor signaling pathways. In addition, the coexpression analysis between lncRNA and mRNA identified 314 nodes and 515 connections between 6 lncRNAs and 308 mRNAs, of which 511 were positive and 4 were negative. Among them, ENSRNOG-00000059555 was strongly correlated with AABR07001160.1. This study revealed multiple lncRNAs were involved in the neuroprotection of 20(R)-Rg3 against CIRI and thereby provided new insights into the use of 20(R)-Rg3 as a novel neuro protectant in ischemic stroke management.

LncRNA MRAK159688 facilitates morphine tolerance by promoting REST-mediated inhibition of mu opioid receptor in rats.

Morphine tolerance (MT) caused by the long-term use of morphine is a major medical problem. The molecular mechanism of morphine tolerance remains elusive. Here, we established a morphine tolerance model in rats and verified whether the long noncoding RNA (lncRNA) MRAK159688 is involved in morphine tolerance and its specific molecular mechanism. We show the significant upregulation of MRAK159688 expression in the spinal cord of morphine-tolerant rats. Overexpression of MRAK159688 by a lentivirus reduces the analgesic efficacy of morphine and induces pain behavior. Downregulation of MRAK159688 using a small interfering RNA (siRNA) attenuates the formation of morphine tolerance, partially reverses the development of morphine tolerance and alleviates morphine-induced hyperalgesia. MRAK159688 is located in the nucleus and cytoplasm of neurons, and it colocalizes with repressor element-1 silencing transcription factor (REST) in the nucleus. MRAK159688 potentiates the expression and function of REST, thereby inhibiting the expression of mu opioid receptor (MOR) and subsequently inducing morphine tolerance. Moreover, REST overexpression blocks the effects of MRAK159688 siRNA on relieving morphine tolerance. In general, chronic morphine administration-mediated upregulation of MRAK159688 in the spinal cord contributes to morphine tolerance and hyperalgesia by promoting REST-mediated inhibition of MOR. MRAK159688 downregulation may represent a novel RNA-based therapy for morphine tolerance.

The possibility of early diagnosis of colorectal cancer through expression of Lncrna UCA1, Lncrna LINC00970, and Wnt genes; an in-vitro study

Colorectal cancer is the 4thcause of cancer death; with considering the growth process of this cancer and the necessity of early diagnosis, the purpose of the research is to state the LncRNA 00970, LncRNA UCAI,and the Wntgene before and after the treatment by 5-Azacytidine epigenetic medicine, to reach the biomarker in the very first steps of colorectal cancer. In this experiment, the human colon cancer cell line (HT29) treated with different concentrations of 5-aza-2'-deoxycytidine (5-aza-dC) was utilized to induce DNA demethylation; Quantitative PCR (qPCR) was used to measure LncRNA UCA1and LncRNA LINC00970 and Wntexpression. There was a significant relationship between the expression of LncRNA 00970, LncRNA UCAI,and the Wntgene and its effects on colorectal (p < 0.05). The Wntgene was treated by 1 and 10 of 5-Azacytidine epigenetic medicine, which then experienced decreases. In LncRNA UCAI and LncRNA00970 in dose 1 micromolar of 5-Azacytidine had decrement and increment of expressionrespectively that explains their efficiency but in treatment by dose 10 mM of this medicine, no significant LncRNA expression difference was detected, 5-azacitidine has a direct impact on its target genes and LncRNAs.Therefore, it can be used in the early diagnosis of colorectal cancer.

Dexmedetomidine inhibits microglial activation through SNHG14/HMGB1 pathway in spinal cord ischemia-reperfusion injury mice.

OBJECTIVE: Microglial activation is an essential pathological mechanism of spinal cord ischemia-reperfusion injury (SCIRI). Previous studies showed dexmedetomidine (DEX) could alleviate SCIRI while the mechanism was not clear. This study aims to investigate the role of DEX in microglial activation and clarify the underlying mechanism. METHODS: The motion function of mice was quantified using the Basso Mouse Scale for Locomotion. The expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) was determined by qRT-PCR. The expression of high-mobility group box 1 (HMGB1) was measured by western blot. The activation of microglia was evaluated by the expression of ED-1 and the levels of TNF-α and IL-6. The interplay between SNHG14 and HMGB1 was confirmed with RNA pull-down and RIP assay. The stability of HMGB1 was measured by ubiquitination assay and cycloheximide-chase assay. RESULTS: DEX inhibited microglial activation and down-regulated SNHG14 expression in SCIRI mice and oxygen and glucose deprivation/reoxygenation (OGD/R)-treated primary microglia. Functionally, SNHG14 overexpression reversed the inhibitory effect of DEX on OGD/R-induced microglial activation. Further investigation confirmed that SNHG14 bound to HMGB1, positively regulated HMGB1 expression by enhancing its stability. In addition, the silence of HMGB1 eliminated the pro-activation impact of SNHG14 overexpression on DEX-treated microglia under the OGD/R condition. Finally, in vivo experiments showed SNHG14 overexpression abrogated the therapeutic effect of DEX on SCIRI mice by up-regulating HMGB1. CONCLUSION: DEX accelerated HMGB1 degradation via down-regulating SNHG14, thus inhibiting microglial activation in SCIRI mice.

The Curcumin Analog EF24 Inhibits Proliferation and Invasion of Triple-Negative Breast Cancer Cells by Targeting the Long Noncoding RNA HCG11/Sp1 Axis.

EF24, a curcumin analog, exerts a potent antitumor effect on various cancers. However, whether EF24 retards the progression of triple-negative breast cancer (TNBC) remains unclear. In this study, we explored the role of EF24 in TNBC and clarified the underlying mechanism. In a mouse model of TNBC xenograft, EF24 administration reduced the tumor volume, suppressed cell proliferation, promoted cell apoptosis, and downregulated long noncoding RNA human leukocyte antigen complex group 11 (HCG11) expression. In TNBC cell lines, EF24 administration reduced cell viability, suppressed cell invasion, and downregulated HCG11 expression. HCG11 overexpression reenhanced the proliferation and invasion of TNBC cell lines suppressed by EF24. The following mechanism research revealed that HCG11 overexpression elevated Sp1 transcription factor (Sp1) expression by reducing its ubiquitination, thereby enhanced Sp1-mediated cell survival and invasion in the TNBC cell line. Finally, the in vivo study showed that HCG11-overexpressed TNBC xenografts exhibited lower responsiveness in response to EF24 treatment. In conclusion, EF24 treatment reduced HCG11 expression, resulting in the degradation of Sp1 expression, thereby inhibiting the proliferation and invasion of TNBC cells.

Paeoniflorin inhibits proliferation and migration of psoriatic keratinocytes via the lncRNA NEAT1/miR-3194-5p/Galectin-7 axis.

To investigate the mechanism underlying the effect of paeoniflorin (PF) on the proliferation and migration of psoriatic keratinocytes. The expressions of long noncoding RNA NEAT1, miR-3194-5p and Galectin-7 in skin tissues from psoriatic patients and healthy controls were detected. Psoriatic HaCat cells were used to investigate the function of NEAT1 and Galectin-7 as well as the effect and mechanism of PF in psoriasis. MTT, colony formation and scratch assays were used to assess the proliferation and migration of psoriatic HaCat cells. Dual-luciferase reporter assay was used to validate the interactions among NEAT1, miR-3194-5p and Galectin-7. NEAT1 and Galectin-7 were lowly expressed and miR-3194-5p was highly expressed in psoriatic patients. PF suppressed the proliferation and migration of psoriatic HaCat cells by elevating the expressions of NEAT1 and Galectin-7. NEAT1 positively mediated the expression of Galectin-7 by targeting miR-3194-5p. PF controls the proliferation and migration of psoriatic HaCat cells via the NEAT1/miR-3194-5p/Galectin-7 axis.

Small Molecule Drugs Targeting Non-Coding RNAs as Treatments for Alzheimer's Disease and Related Dementias.

Despite the enormous burden of Alzheimer's disease and related dementias (ADRD) on patients, caregivers, and society, only a few treatments with limited efficacy are currently available. While drug development conventionally focuses on disease-associated proteins, RNA has recently been shown to be druggable for therapeutic purposes as well. Approximately 70% of the human genome is transcribed into non-protein-coding RNAs (ncRNAs) such as microRNAs, long ncRNAs, and circular RNAs, which can adopt diverse structures and cellular functions. Many ncRNAs are specifically enriched in the central nervous system, and their dysregulation is implicated in ADRD pathogenesis, making them attractive therapeutic targets. In this review, we first detail why targeting ncRNAs with small molecules is a promising therapeutic strategy for ADRD. We then outline the process from discovery to validation of small molecules targeting ncRNAs in preclinical studies, with special emphasis on primary high-throughput screens for identifying lead compounds. Screening strategies for specific ncRNAs will also be included as examples. Key challenges-including selecting appropriate ncRNA targets, lack of specificity of small molecules, and general low success rate of neurological drugs and how they may be overcome-will be discussed throughout the review.

Long non-coding RNA ENST00000414355 as a biomarker of cadmium exposure regulates DNA damage and apoptosis.

Human exposure to cadmium (Cd) may induce severe effects in different organs. Recent studies suggest that long non-coding RNAs (lncRNAs) are closely involved in the pathophysiological mechanisms of Cd-related diseases. This study evaluated the use of lncRNA (ENST00000414355) as an expression signature of Cd exposure and assessed its ability to modulate DNA damage and apoptosis by measuring the expression of ATM serine/threonine kinase (ATM) and mitochondrial membrane potential (ΔΨm) in Cd-exposed workers. A total of 139 (74 non-smokers and 65 smokers) participants from a Cd battery manufacturer were included in the study. Venous blood samples were collected to determine the blood Cd level and detect blood ENST00000414355 and its target gene (ATM) using real-time reverse transcription-polymerase chain reaction (qRT-PCR). Mitochondrial membrane potential was used to assess the Cd effect on mitochondrial permeability. Our results indicated a significant positive correlation between blood Cd level and lncRNA-ENST00000414355 and ATM expression and a significant negative correlation between blood Cd level and ΔΨm (p < 0.0001). Moreover, significant correlations were observed between the expression of lncRNA-ENST00000414355 and ATM expression and ΔΨm (p < 0.0001). Statistical significance was found in the blood Cd level, lncRNA-ENST00000414355 expression, ATM expression, and ΔΨm (p < 0.0001) between smokers and non-smokers. This study confirmed the upregulation of the lncRNA-ENST00000414355 expression, DNA damage-checkpoint-related gene (ATM), and decreased ΔΨm in Cd-exposed workers. Thus, lncRNA-ENST00000414355 may serve as a valuable biomarker for the exposure and toxicity of Cd.

Quercetin promotes bone marrow mesenchymal stem cell proliferation and osteogenic differentiation through the H19/miR-625-5p axis to activate the Wnt/ß-catenin pathway.

BACKGROUND: Quercetin and H19 can promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, whether quercetin regulates H19 expression to promote osteogenic differentiation of BMSCs is unclear. METHODS: BMSC proliferation, matrix mineralization, and alkaline phosphatase (ALP) activity were assessed using the Cell Counting Kit-8, ALP assay kit, and alizarin red staining kit, respectively. Expression of H19, miR-625-5p, BMP-2, osteocalcin, and RUNX2 were measured by qRT-PCR; ß-catenin protein level was measured by western blotting. RESULTS: Quercetin promoted BMSC proliferation, enhanced ALP activity, and upregulated the expression of BMP-2, osteocalcin, and RUNX2 mRNAs, suggesting that it promoted osteogenic differentiation of BMSCs. Moreover, quercetin increased H19 expression, while the effect of quercetin on BMSCs was reversed by silencing H19 expression. Additionally, miR-625-5p, interacted with H19, was downregulated during quercetin-induced BMSC osteogenic differentiation, which negatively correlated with H19 expression. Silencing miR-625-5p expression promoted BMSC proliferation and osteogenic differentiation, whereas miR-625-5p overexpression weakened the effect of quercetin on BMSCs. Finally, quercetin treatment or downregulation of miR-625-5p expression increased ß-catenin protein level in BMSCs. Upregulation or downregulation of miR-625-5p or H19 expression, respectively, inhibited ß-catenin protein level in quercetin treated-BMSCs. CONCLUSION: H19 promotes, while miR-625-5p inhibits BMSC osteogenic differentiation. Quercetin activates the Wnt/ß-catenin pathway and promotes BMSC osteogenic differentiation via the H19/miR-625-5p axis.

Coffee Restores Expression of lncRNAs Involved in Steatosis and Fibrosis in a Mouse Model of NAFLD.

BACKGROUND AND AIM: Coffee intake exerts protective effects against non-alcoholic fatty liver disease (NAFLD), although without fully cleared mechanisms. In this study we aimed to assess whether coffee consumption may influence the expression of long non-coding RNAs (lncRNAs) in the liver. METHODS: C57BL/6J mice were fed a 12-week standard diet (SD), high-fat diet (HFD) or HFD plus decaffeinated coffee solution (HFD + coffee). Expression of specific lncRNAs involved in NAFLD was analyzed by real-time PCR. For the most differentially expressed lncRNAs, the analysis was also extended to their mRNA targets. RESULTS: Decaffeinated coffee intake reduced body weight gain, prevented NAFLD, lowered hyperglycemia and hypercholesterolemia. NAFLD was associated with lower hepatic expression of Gm16551, a lncRNA inhibiting de novo lipogenesis, and higher expression of H19, a lncRNA promoting fibrogenesis. Coffee intake restored Gm16551 to levels observed in lean mice and downregulated gene expression of its targets acetyl coenzyme A carboxylase 1 and stearoyl coenzyme A desaturase 1. Furthermore, coffee consumption markedly decreased hepatic expression of H19 and of its target gene collagen alpha-1(I) chain; consistently, in mice fed HFD + coffee liver expression of αSMA protein returned to levels of mice fed SD. Expression of lncRNA involved in circadian clock such as fatty liver-related lncRNA 1 (FLRL1) and fatty liver-related lncRNA 2 (FLRL2) were upregulated by HFD and were also modulated by coffee intake. CONCLUSION: Hepatoprotective effects of coffee may be depending on the modulation of lncRNAs involved in key pathways of NAFLD onset and progression.

Bifacial PNAs Destabilize MALAT1 by 3' A-Tail Displacement from the U-Rich Internal Loop.

We report herein a new class of synthetic reagents for targeting the element for nuclear expression (ENE) in MALAT1, a long noncoding RNA upregulated in many cancers. The cis-acting ENE contains a U-rich internal loop (URIL) that forms an 11 base UAU-rich triplex stem with the truncated 3' oligo-A tail of MALAT1, protecting the terminus from exonuclease digestion and greatly extending transcript lifetime. Bifacial peptide nucleic acids (bPNAs) similarly bind URILs via base triple formation between two uracil bases and a synthetic base, melamine. We synthesized a set of low molecular weight bPNAs composed of α-linked peptide, isodipeptide, and diketopiperazine backbones and evaluated their ENE binding efficacy in vitro via oligo-A strand displacement and consequent exonuclease sensitivity. Degradation was greatly enhanced by bPNA treatment in the presence of exonucleases, with ENE half-life plunging to 6 min from >24 h. RNA digestion kinetics could clearly distinguish between bPNAs with similar URIL affinities, highlighting the utility of functional assays for evaluating synthetic RNA binders. In vitro activity was mirrored by a 50% knockdown of MALAT1 expression in pancreatic cancer (PANC-1) cells upon treatment with bPNAs, consistent with intracellular digestion triggered by a similar ENE A-tail displacement mechanism. Pulldown from PANC-1 total RNA with biotinylated bPNA enriched MALAT1 > 4000× , supportive of bPNA-URIL selectivity. Together, these experiments establish the feasibility of native transcript targeting by bPNA in both in vitro and intracellular contexts. Reagents such as bPNAs may be useful tools for the investigation of transcripts stabilized by cis-acting poly(A) binding RNA elements.

Identification of Ferroptosis-Related Long Noncoding RNA and Construction of a Novel Prognostic Signature for Gastric Cancer.

BACKGROUND: Gastric cancer is the most common malignant tumor of the digestive system. It has a poor prognosis and is clinically challenging to treat. Ferroptosis is a newly defined mode of programmed cell death. The roles and prognostic value of ferroptosis-related long noncoding RNAs (lncRNAs) in gastric cancer remain unknown. RESULTS: In the current study, 20 ferroptosis-related lncRNAs were identified via univariate Cox analysis, least absolute shrinkage, and selection operator Cox regression analysis and used to construct a prognostic signature and classify gastric cancer patients into high-risk and low-risk groups. The signature was validated using TCGA training and testing cohorts. The risk signature was an independent prognostic indicator of survival and accurately predicted the prognoses of patients with gastric cancer. It was also associated with immune cell infiltration. Gene set enrichment analysis was used to investigate underlying mechanisms that the 20 ferroptosis-related lncRNAs were involved in. Chemosensitivity and immune checkpoint inhibitor analyses indicated that high-risk patients were more sensitive to the immune checkpoint inhibitor programmed cell death protein 1. CONCLUSIONS: The important role of ferroptosis-related lncRNAs in immune infiltration identified in the current study may assist the determination of personalized prognoses and treatments in patients with gastric cancer. These 20 lncRNAs can be used as the diagnostic and prognostic markers for gastric cancer.

Formononetin relieves the facilitating effect of lncRNA AFAP1-AS1-miR-195/miR-545 axis on progression and chemo-resistance of triple-negative breast cancer.

This investigation attempted to discern whether formononetin restrained progression of triple-negative breast cancer (TNBC) by blocking lncRNA AFAP1-AS1-miR-195/miR-545 axis. We prepared TNBC cell lines (i.e. MDA-MB-231 and BT-549) and normal human mammary epithelial cell line (i.e. MCF-10A) in advance, and the TNBC cell lines were, respectively, transfected by pcDNA3.1-lncRNA AFAP1-AS1, si-lncRNA AFAP1-AS1, pcDNA6.2/GW/EmGFP-miR-545 or pcDNA6.2/GW/EmGFP-miR-195. Resistance of TNBC cells in response to 5-Fu, adriamycin, paclitaxel and cisplatin was evaluated through MTT assay, while potentials of TNBC cells in proliferation, migration and invasion were assessed via CCK8 assay and Transwell assay. Consequently, silencing of lncRNA AFAP1-AS1 impaired chemo-resistance, proliferation, migration and invasion of TNBC cells (P<0.05), and over-expression of miR-195 and miR-545, which were sponged and down-regulated by lncRNA AFAP1-AS1 (P<0.05), significantly reversed the promoting effect of pcDNA3.1-lncRNA AFAP1-AS1 on proliferation, migration, invasion and chemo-resistance of TNBC cells (P<0.05). Furthermore, CDK4 and Raf-1, essential biomarkers of TNBC progression, were, respectively, subjected to target and down-regulation of miR-545 and miR-195 (P<0.05), and they were promoted by pcDNA3.1-lncRNA AFAP1-AS1 at protein and mRNA levels (P<0.05). Additionally, formononetin significantly decreased expressions of lncRNA AFAP1-AS1, CDK4 and Raf-1, while raised miR-195 and miR-545 expressions in TNBC cells (P<0.05), and exposure to it dramatically contained malignant behaviors of TNBC cells (P<0.05). In conclusion, formononetin alleviated TNBC malignancy by suppressing lncRNA AFAP1-AS1-miR-195/miR-545 axis, suggesting that molecular targets combined with traditional Chinese medicine could yield significant clinical benefits in TNBC.

Salvianolic Acid A Protects H9C2 Cardiomyocytes from Doxorubicin-Induced Damage by Inhibiting NFKB1 Expression Thereby Downregulating Long-Noncoding RNA (lncRNA) Plasmacytoma Variant Translocation 1 (PVT1).

BACKGROUND A cardioprotective effect of salvianolic acid A (SalA) has been described, but it is unknown whether SalA can protect cardiomyocytes against doxorubicin (Dox)-induced cardiotoxicity. This study aimed to investigate whether SalA could inhibit Dox-induced apoptosis in H9C2 cells and to uncover the potential mechanism. MATERIAL AND METHODS H9C2 cardiomyocytes exposed to Dox were treated with SalA or not, and then cell viability, apoptosis, and the expression of nuclear factor-kappaB (NF-kappaB) signaling were detected by Cell Counting Kit-8, TUNEL staining, and western blot assays, respectively. Nuclear factor kappa B subunit 1 (NFKB1) was overexpressed in H9C2 cells, and then alterations in cell viability and apoptosis in H9C2 cells co-treated with Dox and SalA were investigated. RESULTS SalA (2, 10, and 50 µM) had no effect on H9C2 cell viability, while Dox reduced cell viability in a concentration-dependent manner. In addition, SalA rescued Dox-decreased cell viability. Dox also triggered apoptosis as evidenced by an increased ratio of TUNEL-positive cells, enhanced expression of pro-apoptotic proteins, and reduced expression of anti-apoptotic protein BCL-2, which were all partially blocked by SalA co-treatment. The proteins involved in NF-kappaB signaling including IkappaBalpha, IKKalpha, IKKß, and p65 were activated by Dox but inactivated by SalA co-treatment. Moreover, Dox increased NFKB1 mRNA and nuclear expression, which was blocked by SalA. NFKB1 could bind to plasmacytoma variant translocation 1 (PVT1) and upregulate PVT1 expression. Mechanistically, the overexpression of NFKB1 blocked the inhibitory effect of SalA on Dox-induced cell viability impairment and apoptosis. CONCLUSIONS We demonstrated that SalA may exert a protective effect against Dox-induced H9C2 injury and apoptosis via inhibition of NFKB1 expression, thereby downregulating lncRNA PVT1.

Long non-coding RNAs in neurodegenerative diseases.

Neurodegenerative diseases are gradually becoming the main burden of society. The morbidity and mortality caused by neurodegenerative diseases remain significant health-care concerns. For most neurodegenerative diseases, there are no effective treatments. Over the past few decades, in a quest to exploit efficacious disease-modifying therapies for the treatment of neurodegenerative diseases, disease mechanisms, reliable biomarkers and therapeutic targets have become a research priority. At present, lncRNA is an area with potential research value. In this article, we first summarize some of the existing results of research into lncRNAs, including origin, molecular characteristics, location types, and functional types. We then introduce the possible functions of lncRNAs in different neurodegenerative diseases. Furthermore, some lncRNAs which show promise as biomarkers or potential therapeutic targets are systematically summarized.

Long non-coding RNA H19: Physiological functions and involvements in central nervous system disorders.

Central nervous system (CNS) disorders are some of the most complex and challenging diseases because of the intricate structure and functions of the CNS. Long non-coding RNA (LncRNA) H19, which had been mistaken for "transcription noise" previously, has now been found to be closely related to the development and homeostasis of the CNS. Several recent studies indicate that it plays an important role in the pathogenesis, treatment, and even prognosis of CNS disorders. LncRNA H19 is correlated with susceptibility to various CNS disorders such as intracranial aneurysms, ischemic stroke, glioma, and neuroblastoma. Moreover, it participates in the pathogenesis of CNS disorders by regulating transcription, translation, and signaling pathways, suggesting that it is a promising biomarker and therapeutic target for these disorders. This article reviews the functions and mechanisms of lncRNA H19 in various CNS disorders, including cerebral ischemia, cerebral hemorrhage, glioma, pituitary adenoma, neuroblastoma, Parkinson's disease, Alzheimer's disease, traumatic spinal cord injury, neuropathic pain, and temporal lobe epilepsy, to provide a theoretical basis for further research on the role of lncRNA H19 in CNS disorders.

Astragaloside regulates lncRNA LOC100912373 and the miR­17­5p/PDK1 axis to inhibit the proliferation of fibroblast­like synoviocytes in rats with rheumatoid arthritis.

Previous studies have confirmed that astragaloside (AST) exerts a positive effect on alleviating synovial and joint injury in rheumatoid arthritis (RA). However, the precise mechanisms through which AST acts in the treatment of RA remain unclear. Long non­coding RNA (lncRNA) LOC100912373 was identified as a key gene related to RA and has been proven to interact with miR­17­5p, in order to regulate the pyruvate dehydrogenase kinase 1 and protein kinase B axis (PDK1/AKT axis). The present study aimed to determine whether AST may treat RA through the interaction between lncRNA LOC100912373 and the miR­17­5p/PDK1 axis. MTT assays and flow cytometry were used to detect the proliferation and cell cycle progression of AST­treated fibroblast­like synoviocytes (FLSs). The expression of lncRNA LOC100912373 and miR­17­5p, as well as relative the mRNA expression of the PDK1 and AKT genes following AST intervention was detected by reverse transcription­quantitative PCR (RT­qPCR), immunofluorescence and western blot analysis. The results revealed that AST inhibited FLS proliferation, reduced lncRNA LOC100912373 expression levels, increased miR­17­5p expression levels, and decreased the PDK1 and p­AKT expression levels. Additionally, consecutive rescue experiments revealed that AST counteracted the effects of lncRNA LOC100912373 overexpression on FLS proliferation and cell cycle progression. On the whole, the present study demonstrates that AST inhibits FLS proliferation by regulating the expression of lncRNA LOC100912373 and the miR­17­5p/PDK1 axis.

Dysregulations of long non-coding RNAs - The emerging "lnc" in environmental carcinogenesis.

Long non-coding RNAs (lncRNAs) refer to a class of RNA molecules that are more than 200 nucleotides in length and usually lack protein-coding capacity. LncRNAs play important roles in regulating gene expression as well as many aspects of normal physiological processes. Dysregulations of lncRNA expressions and functions are considered to be critically involved in the development and progression of many diseases especially cancer. The lncRNA research in the field of cancer biology over the past decade reveals that a large number of lncRNAs are dysregulated in various types of cancer and that dysregulated lncRNAs may play important roles in cancer initiation, metastasis and therapeutic responses. Metal carcinogens and other common environmental carcinogens such as polycyclic aromatic hydrocarbons, fine particular matters, cigarette smoke, ultraviolet and ionizing radiation are important cancer etiology factors. However, the mechanisms of how metal carcinogens and other common environmental carcinogen exposures initiate cancer and promote cancer progression remain largely unknown. Accumulating evidence show that exposure to metal carcinogens and other common environmental carcinogens dysregulate lncRNA expression in various model systems, which may offer novel mechanistic insights for environmental carcinogenesis. This review will first provide a brief introduction about lncRNA biology and the mechanisms of lncRNA functions, followed by summarizing and discussing recent studies about lncRNA dysregulation by metal carcinogen and other common environment carcinogen exposures and the potential roles of dysregulated lncRNAs in environmental carcinogenesis. A perspective for future studies in this emerging and important field is also presented.

Megakaryoblastic leukemia: a study on novel role of clinically significant long non-coding RNA signatures in megakaryocyte development during treatment with phorbol ester.

Acute megakaryocytic leukemia (AMKL) is one of the rarest sub-types of acute myeloid leukemia (AML). AMKL is characterized by high proliferation of megakaryoblasts and myelofibrosis of bone marrow, this disease is also associated with poor prognosis. Previous analyses have reported that the human megakaryoblastic cells can be differentiated into cells with megakaryocyte (MK)-like characteristics by phorbol 12-myristate 13-acetate (PMA). However, little is known about the mechanism responsible for regulating this differentiation process. We performed long non-coding RNA (lncRNA) profiling to investigate the differently expressed lncRNAs in megakaryocyte blast cells treated with and without PMA and examined those that may be responsible for the PMA-induced differentiation of megakaryoblasts into MKs. We found 30 out of 90 lncRNA signatures to be differentially expressed after PMA treatment of megakaryoblast cells, including the highly expressed JPX lncRNA. Further, in silico lncRNA-miRNA and miRNA-mRNA interaction analysis revealed that the JPX is likely involved in unblocking the expression of TGF-ß receptor (TGF-ßR) by sponging oncogenic miRNAs (miR-9-5p, miR-17-5p, and miR-106-5p) during MK differentiation. Further, we report the activation of TGF-ßR-induced non-canonical ERK1/2 and PI3K/AKT pathways during PMA-induced MK differentiation and ploidy development. The present study demonstrates that TGF-ßR-induced non-canonical ERK1/2 and PI3K/AKT pathways are associated with PMA-induced MK differentiation and ploidy development; in this molecular mechanism, JPX lncRNA could act as a decoy for miR-9-5p, miR-17-5p, and miR-106-5p, titrating them away from TGF-ßR mRNAs. Importantly, this study reveals the activation of ERK1/2 and PI3K/AKT pathway in PMA-induced Dami cell differentiation into MK. The identified differentially expressed lncRNA signatures may facilitate further study of the detailed molecular mechanisms associated with MK development. Thus, our data provide numerous targets with therapeutic potential for the modulation of the differentiation of megakaryoblastic cells in AMKL.