Non-coding Transcripts Research Articles

Flap endonuclease Rad27 cleaves the RNA of R-loop structures to suppress telomere recombination.

The long non-coding telomeric RNA transcript TERRA, in the form of an RNA-DNA duplex, regulates telomere recombination. In a screen for nucleases that affects telomere recombination, mutations in DNA2, EXO1, MRE11 and SAE2 cause severe delay in type II survivor formation, indicating that type II telomere recombination is mediated through a mechanism similar to repairing double-strand breaks. On the other hand, mutation in RAD27 results in early formation of type II recombination, suggesting that RAD27 acts as a negative regulator in telomere recombination. RAD27 encodes a flap endonuclease that plays a role in DNA metabolism, including replication, repair and recombination. We demonstrate that Rad27 suppresses the accumulation of the TERRA-associated R-loop and selectively cleaves TERRA of R-loop and double-flapped structures in vitro. Moreover, we show that Rad27 negatively regulates single-stranded C-rich telomeric DNA circles (C-circles) in telomerase-deficient cells, revealing a close correlation between R-loop and C-circles during telomere recombination. These results demonstrate that Rad27 participates in telomere recombination by cleaving TERRA in the context of an R-loop or flapped RNA-DNA duplex, providing mechanistic insight into how Rad27 maintains chromosome stability by restricting the accumulation of the R-loop structure within the genome.

CircRNAs and RNA-Binding Proteins Involved in the Pathogenesis of Cancers or Central Nervous System Disorders.

Circular RNAs (circRNAs), a newly recognized group of noncoding RNA transcripts, have established widespread attention due to their regulatory role in cell signaling. They are covalently closed noncoding RNAs that form a loop, and are typically generated during the splicing of precursor RNAs. CircRNAs are key post-transcriptional and post-translational regulators of gene expression programs that might influence cellular response and/or function. In particular, circRNAs have been considered to function as sponges of specific miRNA, regulating cellular processes at the post-transcription stage. Accumulating evidence has shown that the aberrant expression of circRNAs could play a key role in the pathogenesis of several diseases. Notably, circRNAs, microRNAs, and several RNA-binding proteins, including the antiproliferative (APRO) family proteins, could be indispensable gene modulators, which might be strongly linked to the occurrence of diseases. In addition, circRNAs have attracted general interest for their stability, abundance in the brain, and their capability to cross the blood-brain barrier. Here, we present the current findings and theragnostic potentials of circRNAs in several diseases. With this, we aim to provide new insights to support the development of novel diagnostic and/or therapeutic strategies for these diseases.

The long non-coding RNA colon cancer-associated transcript 1-Vimentin axis promoting the migration and invasion of HeLa cells.

Long non-coding RNA colon cancer-associated transcript 1 (CCAT1) is involved in transforming multiple cancers into malignant cancer types. Previous studies underlining the mechanisms of the functions of CCAT1 primarily focused on its decoy for miRNAs (micro RNAs). However, the regulatory mechanism of CCAT1-protein interaction associated with tumor metastasis is still largely unknown. The present study aimed to identify proteome-wide CCAT1 partners and explored the CCAT1-protein interaction mediated tumor metastasis. CCAT1-proteins complexes were purified and identified using RNA antisense purification coupled with the mass spectrometry (RAP-MS) method. The database for annotation, visualization, and integrated discovery and database for eukaryotic RNA binding proteins (EuRBPDB) websites were used to bioinformatic analyzing CCAT1 binding proteins. RNA pull-down and RNA immunoprecipitation were used to validate CCAT1-Vimentin interaction. Transwell assay was used to evaluate the migration and invasion abilities of HeLa cells. RAP-MS method worked well by culturing cells with nucleoside analog 4-thiouridine, and cross-linking was performed using 365 nm wavelength ultraviolet. There were 631 proteins identified, out of which about 60% were RNA binding proteins recorded by the EuRBPDB database. Vimentin was one of the CCAT1 binding proteins and was participated in the tumor metastasis pathway. Knocked down VIM and rescued the downregulation by overexpressing CCAT1 demonstrated that CCAT1 could enhance tumor migration and invasion abilities by stabilizing Vimentin protein. CCAT1 may bind with and stabilize Vimentin protein, thus enhancing cancer cell migration and invasion abilities.

Targeting of the SWI/SNF chromatin remodeling complex in cancer therapy

Chromatin remodeling is the one of the main epigenetic ways of gene expression regulation both in normal cells and in oncological diseases. Genes encoding protein subunits of SWI/ SNF remodeling complexes often mutate and/or change their expression in human tumors, affecting the expression programs of many genes during carcinogenesis, which is associated with the occurrence and progression of cancer. Today, there are no therapeutic drugs that could directly change the structure of chromatin because of complexity of this process with involvement of a large number of genes, proteins, non-coding transcripts and other intermediary molecules. However, the chromatin remodeling complexes can be affected by consistent influence on the subunits and the genes encoding them, as well as the non-coding RNAs that regulate the operation of these complexes and direct them to the target gene regions. Today, several successful strategies have been proposed to influence epigenetic regulators associated with chromatin in order to cause synthetic lethality of cancer cells and block tumor growth. To influence the processes of chromatin remodeling, various strategies and mechanisms are being investigated, from inhibitors of bromodomains of individual subunits to direct effects on the function of SWI/ SNF by destroying its main adenosine triphosphatase subunit. In our review, we analyze the ways and mechanisms of influencing the SWI/ SNF chromatin remodeling complex in order to obtain a stable antitumor effect, from experiments on tumor cells and animal models to the combined use of clinical drugs for the treatment of cancer patients.

An integrated multi-omic approach demonstrates distinct molecular signatures between human obesity with and without metabolic complications: a case–control study

ObjectivesTo examine the hypothesis that obesity complicated by the metabolic syndrome, compared to uncomplicated obesity, has distinct molecular signatures and metabolic pathways.MethodsWe analyzed a cohort of 39 participants with obesity that included 21 with metabolic syndrome, age-matched to 18 without metabolic complications. We measured in whole blood samples 754 human microRNAs (miRNAs), 704 metabolites using unbiased mass spectrometry metabolomics, and 25,682 transcripts, which include both protein coding genes (PCGs) as well as non-coding transcripts. We then identified differentially expressed miRNAs, PCGs, and metabolites and integrated them using databases such as mirDIP (mapping between miRNA-PCG network), Human Metabolome Database (mapping between metabolite-PCG network) and tools like MetaboAnalyst (mapping between metabolite-metabolic pathway network) to determine dysregulated metabolic pathways in obesity with metabolic complications.ResultsWe identified 8 significantly enriched metabolic pathways comprising 8 metabolites, 25 protein coding genes and 9 microRNAs which are each differentially expressed between the subjects with obesity and those with obesity and metabolic syndrome. By performing unsupervised hierarchical clustering on the enrichment matrix of the 8 metabolic pathways, we could approximately segregate the uncomplicated obesity strata from that of obesity with metabolic syndrome.ConclusionsThe data suggest that at least 8 metabolic pathways, along with their various dysregulated elements, identified via our integrative bioinformatics pipeline, can potentially differentiate those with obesity from those with obesity and metabolic complications.

CCAT 1- A Pivotal Oncogenic Long Non-Coding RNA in Colorectal Cancer.

Colorectal cancer (CRC) is ranked as the third most common cancer and second deadliest cancer in both men and women in the world. Currently, the cure rate and 5-year survival rate of CRC patients remain relatively low. Therefore, discovering a novel molecular biomarker that can be used to improve CRC screening, diagnosis, prognosis, and treatment would be beneficial. Long non-coding RNA colon cancer-associated transcript 1 (CCAT 1) has been found overexpressed in CRC and is associated with CRC tumorigenesis and treatment outcome. CCAT 1 has a high degree of specificity and sensitivity, it is readily detected in CRC tissues and is significantly overexpressed in both premalignant and malignant CRC tissues. Besides, CCAT 1 is associated with clinical manifestation and advanced features of CRC, such as lymph node metastasis, high tumor node metastasis stage, differentiation, invasion, and distant metastasis. In addition, they can upregulate oncogenic c-MYC and negatively modulate microRNAs via different mechanisms of action. Furthermore, dysregulated CCAT 1 also enhances the chemoresistance in CRC cells while downregulation of them reverses the malignant phenotypes of cancer cells. In brief, CCAT 1 serves as a potential screening, diagnostic and prognostic biomarker in CRC, it also serves as a potential therapeutic marker to treat CRC patients.

LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition

Long non-coding RNA-myocardial infarction-associated transcript (lncRNA-MIAT) has been reported to play an important role in the development of multiple cancers. However, the biological roles of MIAT in liver fibrosis are still unknown. In this study, the expression of MIAT is up-regulated during liver fibrosis. Silencing MIAT leads to the suppression of hepatic stellate cell (HSC) proliferation and collagen expression. Double immunofluorescence analysis additionally demonstrates that MIAT inhibition leads to the suppression of type I collagen and α-SMA in vitro. In vivo, MIAT knockdown contributes to the inhibition of fibrosis progression and collagen accumulation. MIAT is confirmed as a target of miR-3085-5p, and the co-location of MIAT and miR-3085-5p is found in HSC cytoplasm. Interestingly, there is a negative correlation between MIAT expression and miR-3085-5p level in cirrhotic patients as well as activated HSCs. In addition, the effects of MIAT inhibition on HSC inactivation are blocked down by miR-3085-5p inhibitor. YAP is a target of miR-3085-5p. Reduced YAP caused by loss of MIAT is reversed by miR-3085-5p inhibitor. Notably, YAP knockdown results in the suppression of MIAT-mediated epithelial-to-mesenchymal transition (EMT) process. In conclusion, we demonstrate that MIAT enhances the activation of HSCs, at least in part, via miR-3085-5p/YAP/EMT signaling pathway.

Aberrant lncRNA expression in patients with proliferative diabetic retinopathy: preliminary results from a single-center observational study

BackgroundDiabetic retinopathy (DR) is a leading cause of blindness. Vision threat is particularly severe in patients with retinal neovascularization. However, little is known about the role of long noncoding RNAs (lncRNAs) in proliferative diabetic retinopathy (PDR). The goal of this study was to identify lncRNAs involved in PDR.MethodsWe compared lncRNA expression profiles in the vitreous between patients with PDR and those with idiopathic macular hole (IMH) and between patients with PDR who had received anti-vascular endothelial growth factor (VEGF) therapy and those who had not. Vitreous samples from patients with PDR and IMH were screened for lncRNAs using microarray-based analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the microarray results. Bioinformatic analysis was also performed. Moreover, the effect of anti-VEGF therapy was investigated in vitreous samples of patients with PDR treated with anti-VEGF therapy and those who were not.ResultsA total of 1067 differentially expressed noncoding RNA transcripts were found during screening in the vitreous humor of patients with PDR than in those with IMH. Five lncRNAs were subjected to qRT-PCR. RP11-573 J24.1, RP11-787B4.2, RP11-654G14.1, RP11-2A4.3, and RP11-502I4.3 were significantly downregulated; this was validated by the comparison using the microarray data. In addition, 835 differentially expressed noncoding RNA transcripts were found during screening in the vitreous humor of patients with PDR treated with anti-VEGF therapy compared with untreated PDR patients. RP4-631H13.2 was significantly upregulated, which is consistent with the trend of the microarray analysis.ConclusionsThere were systemic expression differences in the vitreous at the microarray level between patients with PDR and those with IMH and between patients with PDR after anti-VEGF treatment and those that did not receive anti-VEGF treatment. LncRNAs identified in the vitreous humor may be a novel research field for PDR.

Light-dependent signal transduction in the marine diatom Phaeodactylum tricornutum

Unlike most higher plants, unicellular algae can acclimate to changes in irradiance on time scales of hours to a few days. The process involves an enigmatic signaling pathway originating in the plastid that leads to coordinated changes in plastid and nuclear gene expression. To deepen our understanding of this process, we conducted functional studies to examine how the model diatom, Phaeodactylum tricornutum, acclimates to low light and sought to identify the molecules responsible for the phenomenon. We show that two transformants withaltered expressionof twoputativesignal transduction molecules,a light-specific soluble kinase and a plastid transmembrane protein, that appears to be regulated by a long noncoding natural antisense transcript, arising from the opposite strand, are physiologically incapable of photoacclimation. Based on these results, we propose a working model of the retrograde feedback in the signaling and regulation of photoacclimation in a marine diatom.

LncRNA HOTAIRM1 functions in DNA double-strand break repair via its association with DNA repair and mRNA surveillance factors.

The eukaryotic exon junction complex component Y14 participates in double-strand break (DSB) repair via its RNA-dependent interaction with the non-homologous end-joining (NHEJ) complex. Using immunoprecipitation-RNA-seq, we identified a set of Y14-associated long non-coding RNAs (lncRNAs). The lncRNA HOTAIRM1 serves as a strong candidate that mediates the interaction between Y14 and the NHEJ complex. HOTAIRM1 localized to near ultraviolet laser-induced DNA damage sites. Depletion of HOTAIRM1 delayed the recruitment of DNA damage response and repair factors to DNA lesions and compromised the efficiency of NHEJ-mediated DSB repair. Identification of the HOTAIRM1 interactome revealed a large set of RNA processing factors including mRNA surveillance factors. The surveillance factors Upf1 and SMG6 localized to DNA damage sites in a HOTAIRM1-dependent manner. Depletion of Upf1 or SMG6 increased the level of DSB-induced non-coding transcripts at damaged sites, indicating a pivotal role for Upf1/SMG6-mediated RNA degradation in DNA repair. We conclude that HOTAIRM1 serves as an assembly scaffold for both DNA repair and mRNA surveillance factors that act in concert to repair DSBs.

Discovering the Biological Significance and Therapeutic Potential of miR-29b-3p in Triple-Negative Breast Cancer.

The lack of estrogen or progesterone receptors and absence of HER2 amplification/overexpression in triple-negative breast cancer (TNBC) restricts therapeutic options used in clinical management. MicroRNAs (miRNAs) are small, non-coding transcripts which affect important cellular mechanisms by regulating gene expression at the post-transcriptional level. Among this class, attention was focused on miR-29b-3p with a high profile in TNBC and correlated with the overall survival rates, as TCGA data revealed. This study aims to investigate the implication of the miR-29b-3p inhibitor in TNBC cell lines by identifying a potential therapeutic transcript, improving the clinical outcomes of this disease. The experiments were performed on two TNBC cell lines (MDA-MB-231 and BT549) as in vitro models. An established dose of 50 nM was used for all functional assays performed on the miR-29b-3p inhibitor. A decreased level of miR-29b-3p determined a significant reduction in cell proliferation and colony-forming capacity. At the same time, the changes occurring at the molecular and cellular levels were highlighted. We observed that, when inhibiting the expression level of miR-29b-3p, processes such as apoptosis and autophagy were activated. Further, microarray data revealed that the miRNA expression pattern was altered after miR-29b-3p inhibition, pointing out 8 overexpressed and 11 downregulated miRNAs specific for BT549 cells and 33 upregulated and 10 downregulated miRNAs that were specific for MDA-MB-231 cells. As a common signature for both cell lines, three transcripts were observed, two downregulated, miR-29b-3p and miR-29a, and one upregulated, miR-1229-5p. According to DIANA miRPath, the main predicted targets are related to ECM (extracellular matrix) receptor interaction and TP53 signaling. An additional validation step through qRT-PCR was performed, which showed an upregulation of MCL1 and TGFB1. By inhibiting the expression level of miR-29b-3p, it was shown that complex regulatory pathways targeted this transcript in TNBC cells.

Antisense lncRNA CHROMR is linked to glioma patient survival.

Background: Natural non-coding antisense transcripts (ncNATs) are long non-coding RNAs (lncRNA) transcribed from the opposite strand of a separate protein coding or non-coding gene. As such, ncNATs can increase overlapping mRNA (and the coded protein) levels by stabilizing mRNA, absorbing inhibitory miRNAs and protecting the mRNA from degradation, or conversely decrease mRNA (or protein) levels by directing the mRNA towards degradation or inhibiting protein translation. Recently, growing numbers of ncNATs were shown to be dysregulated in cancerous cells, however, actual impact of ncNATs on cancer progression remains largely unknown. We therefore investigated gene expression levels of natural antisense lncRNA CHROMR (Cholesterol Induced Regulator of Metabolism RNA) and its sense protein coding gene PRKRA (Protein Activator of Interferon Induced Protein Kinase EIF2AK2) in gliomas. Next, we checked CHROMR effect on the survival of glioma patients. Methods: We performed RNA-seq on post-surgical tumor samples from 26 glioma patients, and normal brain tissue. Gene expression in TPM values were extracted for CHROMR and PRKRA genes. These data were validated using the TCGA and GTEx gene expression databases. Results: The gene expression level of ncNAT lncRNA CHROMR in glioma tissue was significantly higher compared to healthy brain tissue, while the expression of its sense counterpart protein coding PRKRA mRNA did not differ between glioma and healthy samples. Survival analysis showed lower survival rates in patients with low mRNA PRKRA/lncRNA CHROMR gene expression ratio compared to high ratio showing a link between lncRNA CHROMR and glioma patient survival prognosis. Conclusion: Here we show that elevated levels of lncRNA CHROMR (i.e., low ratio of mRNA PRKRA/lncRNA CHROMR) is associated with poor prognosis for glioma patients.

The MYC-regulated lncRNA LNROP (ENSG00000254887) enables MYC-driven cell proliferation by controlling the expression of OCT2

MYC controls most of the non-coding genome. Several long noncoding transcripts were originally identified in the human B cell line P496-3 and then shown to be required for MYC-driven proliferation of Burkitt lymphoma-derived RAMOS cells. In this study, we used RAMOS cells exclusively as a representative of the human B cell lineage. One of the MYC-controlled lncRNAs required for RAMOS cell proliferation is ENSG00000254887 which we will term LNROP (long non-coding regulator of POU2F2). In the genome, LNROP is located in close proximity of POU2F2, the gene encoding OCT2. OCT2 is a transcription factor with important roles in sustaining the proliferation of human B cells. Here we show that LNROP is a nuclear RNA and a direct target of MYC. Downregulation of LNROP attenuates the expression of OCT2. This effect of LNROP on the expression of OCT2 is unidirectional as downregulation of OCT2 does not alter the expression of LNROP. Our data suggest that LNROP is a cis-acting regulator of OCT2. To illustrate the downstream reach of LNROP, we chose a prominent target of OCT2, the tyrosine phosphatase SHP-1. Downregulation of OCT2 elevates the expression of SHP-1. Our data suggest the following path of interactions: LNROP enables the proliferation of B cells by positively and unidirectionally regulating the growth-stimulatory transcription factor OCT2. In actively proliferating B cells, OCT2 attenuates the expression and anti-proliferative activity of SHP-1.

LncRNA-MALAT1: A Key Participant in the Occurrence and Development of Cancer.

LncRNAs are a group of non-coding RNA transcripts with lengths of over 200 nucleotides and can interact with DNA, RNA, and proteins to regulate gene expression of malignant tumors in human tissues. LncRNAs participate in vital processes, such as chromosomal nuclear transport in the cancerous site of human tissue, activation, and the regulation of proto-oncogenes, the differentiation of immune cells, and the regulation of the cellular immune system. The lncRNA metastasis-associated lung cancer transcript 1 (MALAT1) is reportedly involved in the occurrence and development of many cancers and serves as a biomarker and therapeutic target. These findings highlight its promising role in cancer treatment. In this article, we comprehensively summarized the structure and functions of lncRNA, notably the discoveries of lncRNA-MALAT1 in different cancers, the action mechanisms, and the ongoing research on new drug development. We believe our review would serve as a basis for further research on the pathological mechanism of lncRNA-MALAT1 in cancer and provide evidence and novel insights into its application in clinical diagnoses and treatments.

Long non-coding RNA rhabdomyosarcoma 2-associated transcript contributes to neuropathic pain by recruiting HuR to stabilize DNA methyltransferase 3 alpha mRNA expression in dorsal root ganglion neuron.

Long non-coding RNAs (lncRNAs) act as key regulators in multiple human diseases. In particular, the dysfunction of lncRNAs in dorsal root ganglion (DRG) contributes to the pathogenesis of neuropathic pain (NP). Nevertheless, the role and mechanism of most lncRNAs in NP remain unclear. Two classic chronic NP models, including L4 spinal nerve ligation (SNL) model and chronic constriction injury (CCI) of the sciatic nerve, were performed. Mechanical allodynia and heat hyperalgesia were used to evaluate neuropathic pain. DRG microinjection was used to deliver agents into DRG. qRT-PCR, immunofluorescence, immunoprecipitation, western blotting, siRNA transfection, AAV transduction were performed to investigate the phenotypes and molecular basis. Here, we discovered that Rmst as a lncRNA was specifically expressed in Atf3 + injured DRG neurons and significantly upregulated following peripheral nerve damage. Rmst overexpression by direct DRG injection of AAV5-Rmst causes neuropathic symptoms in the absence of nerve damage. Conversely, blocking Rmst expression in injured DRGs alleviated nerve injury-induced pain hypersensitivities and downregulated Dnmt3a expression. Furthermore, we found peripheral nerve damage induced Rmst increase could interact with RNA-binding protein HuR to stabilize the Dnmt3a mRNA. Our findings reveal a crucial role of Rmst in damaged DRG neurons under NP condition and provide a novel target for drug development against NP.

Dynamic interplay between non-coding enhancer transcription and gene activity in development

Non-coding transcription at the intergenic regulatory regions is a prevalent feature of metazoan genomes, but its biological function remains uncertain. Here, we devise a live-imaging system that permits simultaneous visualization of gene activity along with intergenic non-coding transcription at single-cell resolution in Drosophila. Quantitative image analysis reveals that elongation of RNA polymerase II across the internal core region of enhancers leads to suppression of transcriptional bursting from linked genes. Super-resolution imaging and genome-editing analysis further demonstrate that enhancer transcription antagonizes molecular crowding of transcription factors, thereby interrupting the formation of a transcription hub at the gene locus. We also show that a certain class of developmental enhancers are structurally optimized to co-activate gene transcription together with non-coding transcription effectively. We suggest that enhancer function is flexibly tunable through the modulation of hub formation via surrounding non-coding transcription during development.

LncRNA PANTR1 is Associated with Poor Prognostic and Suppresses Apoptosis in Glioma.

Glioma is the most common tumor in the central nervous system. High-grade gliomas confer a poor prognosis, being a serious health and economic burden. Current literature suggests the important role of long noncoding RNA (lncRNA) in mammals, especially in tumorigenesis of various tumors. The functions of lncRNA POU3F3 adjacent noncoding transcript 1 (PANTR1) have been investigated in hepatocellular carcinoma but remain yet unclear in gliomas. We evaluated the role of PANTR1 in glioma cells using published data from The Cancer Genome Atlas (TCGA), then validated it by ex vivo experiments. To investigate the potential cellular mechanism of different levels of PANTR1 expression in glioma cells, we used siRNA-mediated knockdown in low-grade (grade II) cell lines and GBM (grade IV) cell lines (SW1088 and SHG44, respectively). On the molecular level, low expression of PANTR1 caused significantly reduced glioma cell viability and enhanced cell death. Moreover, we identified the importance of PANTR1 expression for cell migration in both cell lines, a critical foundation for invasiveness in recurrent gliomas. In conclusion, this study provides the first evidence that PANTR1 has a relevant role in human glioma by influencing cell viability and cell death.

Evidence for Existence of Multiple Functional Human Small RNAs Derived from Transcripts of Protein-Coding Genes.

The human genome encodes a multitude of different noncoding transcripts that have been traditionally separated on the basis of their lengths into long (>200 nt) or small (<200 nt) noncoding RNAs. The functions, mechanisms of action, and biological relevance of the vast majority of both long and short noncoding transcripts remain unknown. However, according to the functional understanding of the known classes of long and small noncoding RNAs (sncRNAs) that have been shown to play crucial roles in multiple biological processes, it is generally assumed that many unannotated long and small transcripts participate in important cellular functions as well. Nevertheless, direct evidence of functionality is lacking for most noncoding transcripts, especially for sncRNAs that are often dismissed as stable degradation products of longer RNAs. Here, we developed a high-throughput assay to test the functionality of sncRNAs by overexpressing them in human cells. Surprisingly, we found that a significant fraction (>40%) of unannotated sncRNAs appear to have biological relevance. Furthermore, contrary to the expectation, the potentially functional transcripts are not highly abundant and can be derived from protein-coding mRNAs. These results strongly suggest that the small noncoding transcriptome can harbor multiple functional transcripts that warrant future studies.

A review on the role of long non-coding RNA prostate androgen-regulated transcript 1 (PART1) in the etiology of different disorders.

LncRNA prostate androgen-regulated transcript 1 (PART1) is an important lncRNA in the carcinogenesis whose role has been firstly unraveled in prostate cancer. Expression of this lncRNA is activated by androgen in prostate cancer cells. In addition, this lncRNA has a role in the pathogenesis intervertebral disc degeneration, myocardial ischemia-reperfusion injury, osteoarthritis, osteoporosis and Parkinson's disease. Diagnostic role of PART1 has been assessed in some types of cancers. Moreover, dysregulation of PART1 expression is regarded as a prognostic factor in a variety of cancers. The current review provides a concise but comprehensive summary of the role of PART1 in different cancers and non-malignant disorders.

Long Non-coding RNA XIST Impedes LPS-induced AC16 Cell Inflammation and Apoptosis through Down-regulating miR-370-3p and Regulating PI3K/AKT/mTOR Pathways.

Myocarditis is a severe disorder characterized by the inflammation of the heart's muscular walls, thereby leading to sudden death in young adults. Long non-coding RNA X-inactive specific transcripts (LncRNA XIST) are a class of transcripts having a length ˃ 200 nts with the absence of protein-coding abilities. They exert their function of apoptosis in various cancers and inflammatory diseases. The current work intended to investigate the impact and mechanism of XIST on inflammation induced by LPS in AC16 cells. An in vitro inflammatory injury model was established by stimulating AC16 cells with LPS. CCK-8 was used to test AC16 cell viability and FCM to detect apoptosis. The Elisa assay was used to measure the level of IL-8, IL-1β, and TNF-α. The RT-qPCR was used to detect XIST, miR-370-3p, Bax, and Bcl-2 in LPS-stimulated AC16 cells. The Elisa assay was performed to assess the phosphorylation of PI3K, AKT and mTOR in AC16 cells. Our findings showed LPS exposure to significantly reduce AC16 cell viability while increasing inflammation and apoptosis. Also, XIST expression was reduced in AC16 cells stimulated with LPS. Overexpression of XIST in AC16 cells increased cell survival, inhibited apoptosis, and increased the expressions of Bcl-2, Bax, and inflammatory modulators (IL-8, TNF-α, and IL-1β). Inhibiting XIST in AC16 cells produced opposite outcomes. MiR-370-3p mimics inhibited XIST's effect on inflammation, viability, and apoptosis. Moreover, XIST inhibited the phosphorylation levels of mTOR, AKT, and PI3K in LPS-injured AC16 cells. The data elucidate lncRNA XIST to exert its anti-inflammatory and anti-apoptotic effects on AC16 cells stimulated by LPS via down-regulating miR-370-3p and inhibiting PI3K/AKT/mTOR pathways. These findings suggest a novel treatment strategy for myocarditis.