lncRNA DLX6-AS1 Research Articles

ZC3H13 knockdown enhances the inhibitory effect of sevoflurane on gastric cancer cell malignancy by regulating the N6-methyladenosine modification of the lncRNA DLX6-AS1

Sevoflurane, an inhalation anesthetic, has been shown to suppress cancer development. In this study, we investigated the specific mechanisms involving sevoflurane, zinc-finger CCCH-type containing 13 (ZC3H13), and lncRNA DLX6-AS1 in gastric cancer (GC) progression, focusing on the N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs). We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses to measure the levels of ZC3H13 and lncRNA DLX6-AS1 in GC tissues and cells. Furthermore, we conducted Cell Counting Kit-8, colony formation, Transwell, and tumor xenograft assays to evaluate changes in GC cell malignancy following cell transfection and sevoflurane treatment. Additionally, actinomycin D, methylated RNA immunoprecipitation, and qRT-PCR assays were performed to examine the regulatory effects of ZC3H13 on the DLX6-AS1 m6A modification. We detected elevated levels of ZC3H13 in GC samples, while ZC3H13 silencing inhibited GC cell proliferation, migration, and invasion. Silencing ZC3H13 also enhanced the inhibitory effects of sevoflurane on GC cell malignancy. Moreover, we found that the increased expression of DLX6-AS1 in GC cells could be suppressed by ZC3H13 through the mediation of the m6A modification of DLX6-AS1, thereby reducing DLX6-AS1 stability. In conclusion, ZC3H13 knockdown enhances the inhibitory effect of sevoflurane on GC cell malignancy by inducing DLX6-AS1 m6A modification. Our findings may help identify potential therapeutic targets for the treatment of GC.

The Antidepressant Action of Fluoxetine Involves the Inhibition of Dlx5/6 in Cortical GABAergic Neurons through a TrkB-Dependent Pathway.

Major depressive disorder (MDD) is a complex and devastating illness that affects people of all ages. Despite the large use of antidepressants in current medical practice, neither their mechanisms of action nor the aetiology of MDD are completely understood. Experimental evidence supports the involvement of Parvalbumin-positive GABAergic neurons (PV-neurons) in the pathogenesis of MDD. DLX5 and DLX6 (DLX5/6) encode two homeodomain transcription factors involved in cortical GABAergic differentiation and function. In the mouse, the level of expression of these genes is correlated with the cortical density of PV-neurons and with anxiety-like behaviours. The same genomic region generates the lncRNA DLX6-AS1, which, in humans, participates in the GABAergic regulatory module downregulated in schizophrenia and ASD. Here, we show that the expression levels of Dlx5/6 in the adult mouse brain are correlated with the immobility time in the forced swim test, which is used to measure depressive-like behaviours. We show that the administration of the antidepressant fluoxetine (Flx) to normal mice induces, within 24 h, a rapid and stable reduction in Dlx5, Dlx6 and Dlx6-AS1 expression in the cerebral cortex through the activation of the TrkB-CREB pathway. Experimental Dlx5 overexpression counteracts the antidepressant effects induced by Flx treatment. Our findings show that one of the short-term effects of Flx administration is the reduction in Dlx5/6 expression in GABAergic neurons, which, in turn, has direct consequences on PV expression and on behavioural profiles. Variants in the DLX5/6 regulatory network could be implicated in the predisposition to depression and in the variability of patients' response to antidepressant treatment.

Lipid nanoparticle-encapsulated lncRNA DLX6-AS1 knockdown ameliorates cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis

ABSTRACT Objective Cerebral ischemia is a neurological disorder that leads to permanent disability. This research focuses on exploring the ameliorative effects of lipid nanoparticle (LNP)-encapsulated lncRNA DLX6-AS1 knockdown in cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis. Methods LNP-encapsulated lncRNA DLX6-AS1 was prepared. Cerebral ischemic injury mouse models were established utilizing middle cerebral artery occlusion (MCAO). The mice were treated by intravenous injection of LNP-encapsulated lncRNA DLX6-AS1. The neurological deficits, Inflammatory factor levels, pathological characteristics were observed. In vitro N2a cell oxygen and glucose deprivation (OGD) models were established, and the cells were treated with LNP-encapsulated lncRNA DLX6-AS1 or Nrf2 inhibitor (ML385). Cell viability and apoptosis were tested. DLX6-AS1, Nrf2, HO-1, and NLRP3 expression levels were assessed. Results LncRNA DLX6-AS1 levels were elevated in the brain tissues of mice with cerebral ischemic injury and OGD-induced N2a cells. LNP-encapsulated DLX6-AS1 siRNA (si-DLX6-AS1) improved neurological deficit scores, reduced the levels of inflammatory factors, improved brain tissue pathological damage, and raised the number of survival neurons in CA1. LNP-encapsulated si-DLX6-AS1 ameliorated the OGD-induced N2a cell viability decrease and apoptosis rate increase, and ML385 (Nrf2 inhibitor) reversed the ameliorative effects of LNP-encapsulated si-DLX6-AS1. In cerebral ischemic injury mice and OGD-induced N2a cells, Nrf2 and HO-1 levels were reduced and NLRP3 levels were increased. LNP-encapsulated si-DLX6-AS1 raised Nrf2 and HO-1 levels and reduced NLRP3 levels. Nrf2 inhibitor ML385 treatment reversed the ameliorative effects of LNP-encapsulated si-DLX6-AS1 on OGD-induced N2a cell viability and apoptosis. Conclusion Lipid nanoparticle-encapsulated si-DLX6-AS1 ameliorates cerebral ischemic injury via the Nrf2/HO-1/NLRP3 axis.

Abstract 2079: Single-cell And Spatially Resolved Transcriptome Analysis Reveals A Novel Lncrna Regulator Of Human Atherosclerosis

Cardiovascular diseases, such as atherosclerosis, are the major cause of death in Western societies. Still, molecular mechanisms of plaque destabilization remain unclear. Vascular Smooth Muscle Cells (VSMCs) are the most abundant cell type in atherosclerotic lesions. These cells keep their plasticity also with disease progression and are, therefore, an ideal target cell type for potential therapies. Long non-coding RNAs (lncRNAs) are one example of highly cell type- and disease-state-specific novel molecular modulators. We utilized combined total (bulk) RNA and single cell (sc) RNA sequencing of advanced human carotid artery lesions (patients who underwent carotid endarterectomy in our vascular surgery clinic) to discover novel regulators. Additionally, we performed hybridization-based RNA in situ sequencing (HybRISS, Xenium) to indicate where these genes are located within the plaques. We also performed scSeq in our inducible carotid artery plaque rupture mice ( ApoE-/- ). In vivo and in vitro modulation (KD; knock-down) of the newly identified lncRNA DLX6-AS1 ( D istal- L ess Homeobo x 6 A nti s ense 1 ) using Antisense LNA (Locked nucleic acid) GapmeRs is performed in this mouse model as well as in primary human VSMC culture. DLX6-AS1 shows a highly specific expression pattern in a distinct sub-cluster of VSMCs, as well as a striking location within human atherosclerotic lesions shown by spatial transcriptomics in advanced plaques. DLX6-AS1 is mainly expressed in the nucleus of cells, and KD of this lncRNA leads to changes in VSMC behavior in vitro and in vivo . The KD also has only little effect on the other genes of this locus, DLX6 and DLX5 ( D istal- L ess Homeobo x 6 and 5 ) We found Dlx6os1 ( D istal- l ess homeobo x 6, o pposite s trand 1 ) in our scRNA-seq dataset of the inducible carotid artery plaque rupture mice ( ApoE-/- ) where the KD leads to an increased plaque rupture rate. Taken together, our datasets, methods, and animal models demonstrate that utilizing bulk- and scRNA-seq data, together with spatially resolved sequencing methods, are powerful tools to identify and characterize novel lncRNA regulators that can facilitate fate decisions in VSMCs in atherosclerosis. DLX6-AS1 is one of these novel regulators and will be further analyzed in vivo and in vitro .

MiR-141-3p Enhanced Radiosensitivity of CRC Cells.

Colorectal cancer (CRC) is recognized as one of the frequently diagnosed malignancies, and numerous microRNAs (miRs) are identified to be active in CRC. This work aimed to clarify the effect of miR-141-3p on the radiosensitivity of CRC cells. Firstly, CRC cell lines were cultured and applied to construct radiation-resistant CRC cells via X-ray treatment. The expression levels of miR-141-3p and long non-coding RNA DLX6 antisense RNA 1 (lncRNA DLX6-AS1) in CRC cells were measured using real-time quantitative polymerase chain reaction. After transfection with miR-141-3p mimics and 24 h treatment with 6- MV X-ray (0, 2, 4, 6 Gy), the survival fraction (SF) and the colony formation ability of CRC cells were determined using the cell counting kit-8 and colony formation methods. The interactions between miR-141-3p and DLX6-AS1 were analyzed using the dual-luciferase assay. The impact of miR-141-3p on DLX6-AS1 stability was detected after adding actinomycin-D. The role of DLX6- AS1 in the radiosensitivity of CRC cells was explored by transfecting oe-DLX6-AS1 into radiation- resistant CRC cells overexpressing miR-141-3p. The relative expression levels of miR-141-3p were downregulated in CRC cells and further declined in radiation-resistant cells. Upregulation of miR-141-3p relative expression reduced SF and the colony formation ability while amplifying the radiosensitivity of radiation-resistant CRC cells. miR-141-3p directly bound to DLX6-AS1 to reduce DLX6-AS1 stability, and therefore downregulated DLX6-AS1 expression. DLX6-AS1 overexpression counteracted the role of miR- 141-3p overexpression in amplifying the radiosensitivity of radiation-resistant CRC cells. miR-141-3p binding to DLX6-AS1 significantly decreased DLX6-AS1 stability and expression, promoting the radiosensitivity of CRC cells.

Expression and function of long non-coding RNA DLX6-AS1 in endometrial cancer

Background: LncRNA DLX6-AS1 has been uncovered to exert effects on various cancers. Nevertheless, the impacts of DLX6-AS1 on endometrial cancer (EC) development remained obscure. The study explored the influence of DLX6-AS1 on EC progression via the microRNA (miR)-374a-3p/zinc-finger protein (ZFX) axis.Methods: EC cell lines were collected and DLX6-AS1, miR-374a-3p, and ZFX levels in EC cell lines were detected. The EC cells were transfected with DLX6-AS1, miR-374a-3p, and ZFX constructs to examine the biological functions of EC cells. The xenograft model was established for detecting tumor growth. Rescue experiments were conducted to verify the interaction of DLX6-AS1, miR-374a-3p, and ZFX in EC cells.Results: DLX6-AS1 and ZFX levels were elevated, while miR-374a-3p exhibited a reduced level in EC cells. Silencing DLX6-AS1 and elevated miR-374a-3p expressions repressed the biological activities of EC cells. Reduced DLX6-AS1 repressed tumor development. MiR-374a-3p silencing reversed the impacts of DLX6-AS1 silencing, while ZFX overexpression abrogated the impacts of miR-374a-3p elevation on EC cell growth. Mechanically, DLX6-AS1 was found to bind to miR-374a-3p, and miR-374a-3p targeted ZFX.Conclusion: DLX6-AS1 depletion restricts the malignant phenotype of EC cells. The study might provide novel therapeutic biomarkers for EC treatment.

Association between lncRNAs in plasma exosomes and diabetic retinopathy.

BackgroundLong noncoding RNA (lncRNA) in plasma exosomes is a potential non-invasive diagnostic biomarker for diabetic retinopathy (DR). However, the changes in plasma exosomal lncRNAs and diagnostic relevance in patients with DR patients remain unclear.MethodsA case–control study with type 2 diabetes mellitus (T2DM) and patients with comorbid DR were enrolled, and their clinical information and blood samples were collected. Plasma exosomes were extracted, and the relative expression levels of representative differentially expressed exosomal lncRNAs were determined. A logistic regression model was used to analyze the relationships of DR with relative lncRNA expression and DR-related factors, and receiver operating characteristic (ROC) curve analysis was used to evaluate the value of exosomal lncRNAs for DR diagnosis.ResultsSixty-two patients with T2DM and sixty-two patients with DR were matched by age, sex, and disease duration. The fasting blood glucose concentration, glycosylated hemoglobin level (HbA1c), and relative expression of the plasma exosomal lncRNA DLX6-AS1 were significantly higher in the DR group than in the T2DM group, whereas the 2-h C-peptide concentration and relative expression of the lncRNAs PRINS and FAM190A-3 were lower in the DR group. After adjusting for relevant confounders, the fasting blood glucose concentration, HbA1c level, 2-h C-peptide concentration, and relative expression of lncRNA DLX6-AS1, PRINS, and FAM190A-3 were found to be associated with DR. Both DLX6-AS1 [area under the curve (AUC): 0.658 (0.562–0.754)], PRINS [AUC: 0.798 (0.722–0.873)], and FAM190A-3 [AUC: 0.603 (0.503-0.702)] expression had predictive value for DR diagnosis. The combination of DLX6-AS1 and PRINS yielded an AUC of 0.813 (0.740–0.886). In males, the combination of DLX6-AS1 and PRINS yielded an AUC of 0.860 (0.780–0.940).ConclusionThe fasting blood glucose concentration, HbA1c level, and exosomal DLX6-AS1 expression were identified as risk factors for DR, whereas the 2-h C-peptide concentration and exosomal PRINS and FAM190A-3 were identified as protective against DR. The combination of exosomal DLX6-AS1 and PRINS had good diagnostic value for DR in the general population and males. More attention should be paid to the role of exosomal PRINS expression as a predictive and diagnostic DR biomarker in females.

Strategies of LncRNA DLX6-AS1 on Study and Therapeutics.

Accumulating evidence has revealed the vital regulatory roles of lncRNA DLX6-AS1 in various tumors at pre-transcriptional, transcriptional, and post-transcriptional levels, which makes it a potential prognosis factor and therapeutic target. In addition, the presence of lncRNA DLX6-AS1 in the exosomes of peripheral blood of patients with tumors may also contribute to it being a possible cancer-related biomarker. However, most literature studies are devoted to studying the effect of lncRNA DLX6-AS1 as a sponging molecule of miRNAs, the research of which is likely to get stuck into a dilemma. Literature studies published already have demonstrated an exciting cell malignant phenotype inhibition with the knockdown of lncRNA DLX6-AS1 in various tumor cell lines. With the comprehensive development of delivery systems, high-throughput sequencing, and aptamers, the problems of finding novel research methods and exploring the therapeutic options which are based on lncRNA DLX6-AS1 in vivo could come into a period to deal with. This review aims to summarize the research statuses of lncRNA DLX6-AS1, discuss other study methodologies and therapeutic strategies on it, which might be of help to the deep learning of lncRNA DLX6-AS1 and its application from basic to clinical research.

Retraction Note: Down-regulated lncRNA DLX6-AS1 inhibits tumorigenesis through STAT3 signaling pathway by suppressing CADM1 promoter methylation in liver cancer stem cells

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-019-1239-3.

POS-357 CAMP-RESPONSE ELEMENT BINDING PROTEIN MEDIATES PODOCYTE INJURY IN DIABETIC NEPHROPATHY BY TARGETING LNCRNA DLX6-AS1

Diabetic nephropathy (DN) is one of the most severe microvascular complications of diabetic mellitus, and main cause of renal failure in patients with end-stage renal disease. In our previous study, lncRNA DLX6-AS1 (DLX6-AS1, Dlx6-os1 in mice) was found to be associated with the extent of albuminuria in DN patients. Furthermore, the lack of Dlx6-os1 was pivotal in switching off the inflammatory response in a diabetic mouse model. However, the regulatory factors responsible for elevated DLX6-AS1 in DN remains unknown.

CAMP-response element binding protein mediates podocyte injury in diabetic nephropathy by targeting lncRNA DLX6-AS1

BackgroundProgressive proteinuria is one of the earliest clinical features of diabetic nephropathy (DN). In our previous study, lncRNA DLX6-AS1 (DLX6-AS1, Dlx6os1 in the mouse) was found to be associated with the extent of albuminuria in DN patients. Furthermore, the lack of Dlx6os1 was pivotal in switching off the inflammatory response in db/db mouse model. However, the regulatory factors responsible for elevated DLX6-AS1 in DN remains unknown. MethodsTo identify potential regulatory factors for DLX6-AS1, JASPAR database and DNA pull down combined subsequent liquid chromatography-tandem mass spectrometry were used. Dual-luciferase reporter assay and chromatin immunoprecipitation were then performed to confirm binding sites. We also investigated the effects of the regulatory factors on DN progression in db/db mouse model and cultured human podocytes. ResultsOur analyses demonstrated that cAMP-response element binding protein (CREB) was highly expressed and closely associated with DLX6-AS1 in DN. In db/db mouse and in cultured podocytes, CREB silencing significantly reduced the level of DLX6-AS1 or Dlx6os1 and attenuated renal damage. Mechanistically, CREB overexpression aggravated renal inflammation and destroyed the structure of podocytes by targeting DLX6-AS1. The damaging role of CREB in podocyte injury was also inhibited by 666–15, a selective inhibitor, in a dose-dependent manner. In vivo, the inhibition of CREB by 666–15 significantly attenuated albuminuria and ameliorated inflammatory infiltration in podocytes. ConclusionsOur findings indicated that CREB is a key mediator of podocyte injury and acts by regulating DLX6-AS1. Thus, CREB may be an effective and potential therapeutic target for the treatment of DN.

LncRNA DLX6-AS1 regulates osteosarcoma progression via the miR-200a-3p/GPM6P axis

LncRNA DLX6-AS1 takes part in the progression of various cancers. However, it is not elaborated clearly in osteosarcoma (OS) development. Therefore, we aimed to explore the impacts and specific mechanisms of DLX6-AS1 on the progression of OS. We estimated the pattern of DLX6-AS1 expression in Ost tissues and cells via quantitative reverse transcription polymerase chain reaction. A number of biochemical assays were carried out to assess the effects of DLX6-AS1. Target genes were predicted by bioinformatics methods. Then we used the transfection of si-RNA, miRNA inhibitor, and miRNA mimics to explore the underlying mechanisms and built tumor xenograft models for the in vivo experiments. A higher expression of DLX6-AS1 was found in OS tissues and cell lines, while knockdown of DXL6-AS1 suppressed OS cell metastasis and proliferation in vitro and in vivo. Mechanistically, it was revealed that DXL6-AS1 sponged miR-200a-3p, thus positively regulating the downstream GPM6B. In summary, DLX6-AS1 knockdown would inhibit OS cell migration, cell invasion, and cell proliferation, in which the DXL6-AS1/ miR-200a-3p/ GPM6B axis played a critical role.

Serum Exosomal lncRNA DLX6-AS1 Is a Promising Biomarker for Prognosis Prediction of Cervical Cancer.

Objective:Deregulation of long noncoding RNAs (lncRNAs) is involved in the initiation and progression of cancer. LncRNA DLX6-AS1 is regarded as an oncogene in many cancer types. However, the clinical role of serum exosomal lncRNA DLX6-AS1 in cervical cancer (CC) is poorly known. This study aimed to analyze the diagnostic and prognostic value of serum exosomal lncRNA DLX6-AS1 in CC.Methods:A total of 114 patients with CC, 60 patients with CIN (cervical intraepithelial neoplasia), and 110 healthy women were enrolled in this study. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure the serum exosomal lncRNA DLX6-AS1 levels in all participants.Results:Serum exosomal lncRNA DLX6-AS1 level was significantly elevated in CC patients compared with CIN patients and normal controls. In addition, high serum exosomal lncRNA DLX6-AS1 expression was positively associated with lymph node metastasis, differentiation, FIGO stage, and shortened survival. Patients with high serum exosomal lncRNA DLX6-AS1 expression were more prone to have a relapse. Furthermore, univariate and multivariate analyses suggested that serum exosomal lncRNA DLX6-AS1 was a potential prognostic indicator for overall survival of CC patients.Conclusions:These findings demonstrated that serum lncRNA DLX6-AS1 might serve as a promising marker for the diagnosis and prognosis prediction of CC.

DLX6-AS1: An Indispensable Cancer-related Long Non-coding RNA.

There is increasing evidence that lncRNA, a type of transcript that is over 200 nucleotides in length and may serve as oncogenes or suppressor genes, is implicated in the pathophysiology of human diseases. In particular, tumorigenesis and progress are closely correlated with its abnormal expression. In addition, it may become a promising target for many oncology biotherapies. Abnormal DLX6-AS1 expression affects different cellular processes such as proliferation, aggression and metastasis. This review aims to probe into the pathophysiological functions and molecular mechanisms of DLX6-AS1 in various cancers. By retrieving the literature, this review summarizes the biological function and mechanism of LncRNA DLX6-AS1 in tumor occurrence. The lncRNA DLX6-AS1 is a new tumor-related RNA that has recently been found to be aberrantly expressed in diverse cancers, such as pancreatic cancer, osteosarcoma, non-small cell lung cancer, gastric carcinoma, glioma, hepatocellular cancer, colorectal carcinoma, renal carcinoma, esophageal squamous cell cancer, ovarian cancer, Ewing sarcoma, cervical cancer, breast cancer, thyroid cancer, neuroblastoma, pulmonary adenocarcinoma, nasopharyngeal carcinoma, squamous laryngeal cancer and bladder cancer, etc. Meanwhile, it is identified that DLX6-AS1 regulates the aggression, translocation and proliferation of diverse cancers. LncRNA DLX6-AS1 may be viable markers in tumors or a potential therapeutic target for multiple tumors.

RETRACTED: LncRNA DLX6-AS1 Promotes Malignant Phenotype and Lymph Node Metastasis in Prostate Cancer by Inducing LARGE Methylation

Long non-coding RNAs (lncRNAs) have recently become recognized as crucial players in cancer cellular events including proliferation, migration, and invasion. Herein, we investigated the potential role of lncRNA DLX6-AS1 in prostate cancer cell malignant behaviors and lymph node metastasis. A differentially expressed lncRNA DLX6-AS1 and its downstream regulatory gene (LARGE) were predicted by analysis in silico. RT-qPCR and western blot analysis results demonstrated that DLX6-AS1 was highly expressed, but LARGE was poorly expressed in prostate cancer tissues and cells. The online website indicated that DLX6-AS1 negatively targeted LARGE expression, which was validated by Pearson correlation analysis and MSP. ChIP, RIP, and RNA pull-down assays further suggested that DLX6-AS1 downregulated LARGE expression through recruitment of DNMT1 to its promoter. We induced DLX6-AS1/LARGE overexpression or knockdown to examine their effects through Edu and Transwell assays, which revealed that DLX6-AS1 overexpression accelerated proliferation, invasion, and migration of prostate cancer cells, and that overexpression of LARGE rescued these effects. Tumors xenografts studies confirmed that DLX6-AS1 promoted lymph node metastasis by regulating LARGE, as evidenced by enhanced expression of MMP-9, uPAR, and cathepsin B. In summary, DLX6-AS1 stimulated prostate cancer malignant progression and lymph node metastasis by inducing DNMT1-mediated LARGE methylation, highlighting a potential therapeutic target against prostate cancer.

Long non-coding RNA DLX6-AS1 facilitates bladder cancer progression through modulating miR-195-5p/VEGFA signaling pathway.

In this study, we aim at investigating the expression and regulation role of long non-coding RNA (lncRNA) DLX6-AS1 in bladder cancer (BC). DLX6-AS1 was highly expressed in BC tissues and significant negative correlation with the 5-year survival in the BC patients. The results showed that the proliferation, migration and invasion activities of BC cells were promoted by DLX6-AS1 overexpression, while cell apoptosis was repressed. However, knockdown DLX6-AS1 presented an pposite regulatory effect, and DLX6-AS1 knockdown delayed tumor in vivo. The potential target of DLX6-AS1 in BC was predicted and verified by RIP, RNA pull-down, and dual-luciferase reporter assays as miR-195-5p. The results showed that miR-195-5p was down-regulated in BC tissues, the expression of which was significantly negative correlated with DLX6-AS1 expression. In addition, the results also showed that miR-195-5p targeted and down-regulated the VEGFA. Knockdown of DLX6-AS1 up-regulated miR-195-5p expression and down-regulated VEGFA expression. Moreover, down-regulation of VEGFA expression caused by DLX6-AS1 inhibited phosphorylation of Raf-1, MEK1/2, and ERK1/2, while miR-195-5p inhibitors abolished the effect of silencing DLX6-AS1 expression. Our study demonstrated that DLX6-AS1 played an oncogenic role in BC through miR-195-5p-mediated VEGFA/Ras/Raf/MEK/ERK pathway.

<p>LncRNA DLX6-AS1 Promotes the Progression of Neuroblastoma by Activating STAT2 via Targeting miR-506-3p</p>

BackgroundNeuroblastoma (NB) is a common malignant tumor of the sympathetic nervous system, mainly disturbing children. Long non-coding RNAs (lncRNAs) serving as promising cancer biomarkers have been well recognized. Our study intends to explore the functions of lncRNA X–inactive specific transcript (DLX6-AS1) in NB and provide a potential action mechanism.MethodsThe expression of DLX6-AS1, miR-506-3p and signal transducer and activator of transcription 2 (STAT2) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Cell cycle distribution was determined by flow cytometry assay. The protein level of cell cycle-related markers and STAT2 was detected by Western blot. Glycolysis progress was evaluated according to glucose consumption, lactate production and ATP level. The target genes were predicted by the online database Starbase3.0 and verified by dual-luciferase reporter assay.ResultsDLX6-AS1 expression was highly elevated in NB tissues and cells. DLX6-AS1 deficiency inhibited NB cell proliferation, cell cycle and glycolysis in vitro. MiR-506-3p was a target of DLX6-AS1, and miR-506-3p absence partly reversed the effects of DLX6-AS1 deficiency. Besides, STAT2 was targeted by miR-506-3p, and its expression was regulated by DLX6-AS1 through miR-506-3p. MiR-506-3p restoration also inhibited NB cell malignant behaviors, and STAT2 overexpression partially abolished the role of miR-506-3p restoration. Moreover, DLX6-AS1 deficiency weakened tumor growth in vivo.ConclusionDLX6-AS1 regulated cell proliferation, cell cycle and glycolysis in vitro and tumor growth in vivo to promote the development of NB by upregulating STAT2 via targeting miR-506-3p.

Long noncoding RNA DLX6-AS1 functions as a competing endogenous RNA for miR-577 to promote malignant development of colorectal cancer.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA DLX6-AS1 functions as a competing endogenous RNA for miR-577 to promote malignant development of colorectal cancer, by F.-R. Zhou, Z.-P. Pan, F. Shen, L.-Q. Huang, J.-H. Cui, K. Cai, X.-L. Guo, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3742-3748-DOI: 10.26355/eurrev_201905_17800-PMID: 31115000" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17800.

LncRNA DLX6-AS1 Promotes Proliferation of Laryngeal Cancer Cells by Targeting the miR-26a/TRPC3 Pathway.

PurposeLaryngeal cancer is the most prevalent tumor type in head and neck cancers. Early diagnosis is considered as an important strategy for improving prognosis. The lncRNA DLX6-AS1 has been shown to modulate tumor phenotypes in several types of cancer, but the role of DLX6-AS1 in laryngeal cancer and its concrete mechanisms are not clear.MethodsTissue samples from laryngeal cancer patients and corresponding clinical data were used for detailed analysis. The laryngeal cancer cell lines HEp-2 and Tu-177 were studied. Cell proliferation, ROS production, mitochondrial respiratory function, intracellular and mitochondrial calcium influx were assessed. Western blotting, quantitative RT-PCR and luciferase assays were used to analyze the interactions. A xenografted tumor model was established to analyze the effects of DLX6-AS1 on tumor growth in vivo.ResultslncRNA DLX6-AS1 had increased expression in tumor tissues compared with adjacent normal tissues and in higher clinical stages compared with lower stages, which was associated with poor prognosis. In detail, DLX6-AS1 knockdown decreased cell proliferation and affected key mitochondrial metabolic parameters in both HEp-2 and Tu-177 cells. Moreover, DLX6-AS1 knockdown suppressed TRPC3-mediated mitochondrial calcium uptake and ROS production. Furthermore, miR-26a functioned as a link between these two molecules, as it could be absorbed by DLX6-AS1 and thus regulated the levels of TRPC3. Finally, the DLX6-AS1/miR-26a/TRPC3 axis modulated laryngeal cancer proliferation both in vitro and in vivo.ConclusionThis study provides new evidence that a novel lncRNA, DLX6-AS1, regulates mitochondrial calcium homeostasis, respiration and tumor proliferation via modulating the miR-26a/TRPC3 axis in laryngeal cancer.

Long Noncoding RNA DLX6-AS1 Promotes the Progression in Cervical Cancer by Targeting miR-16-5p/ARPP19 Axis.

Background: Cervical cancer (CC) is regarded as one of the most common gynecological malignancies. LncRNA DLX6-AS1 has been proven vital in various cancers, whereas its exact function is still largely unestablished in CC. Materials and Methods: The expression pattern of DLX6-AS1 and miR-16-5p in CC cells was determined by real-time quantitative polymerase chain reaction (RT-qPCR). ARPP19 expression was assessed by RT-qPCR and Western blot assays in CC cells. The precise function of DLX6-AS1 in CC was detected by Cell-Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), caspase-3 activity, transwell, and Western blot experiments. RNA immunoprecipitation (RIP) and luciferase reporter assays were employed to certify the combination between miR-16-5p and DLX6-AS1 (or ARPP19). Nuclear cytoplasmic segmentation determined the localization of DLX6-AS1 in CC cells. A xenograft mouse model assay studied the influences of DLX6-AS1 silencing on CC progression in vivo. Results: Elevated DLX6-AS1 expression was disclosed in CC cells. DLX6-AS1 silence attenuated proliferation, migration, and epithelial-mesenchymal transition program as well as enhanced CC cell apoptosis. DLX6-AS1 was uncovered to sponge and negatively modulate miR-16-5p in CC. Besides, ARPP19 was uncovered as a downstream target gene of miR-16-5p in CC. Rescue experiments indicated that DLX6-AS1 enhanced the cellular process of CC cells through upregulating ARPP19. Moreover, in vivo assay confirmed that DLX6-AS1 promoted CC growth. Conclusions: DLX6-AS1 accelerates the progression of CC through sponging miR-16-5p and upregulates ARPP19, which offers a novel insight into prognosis and remedy of CC.