Protein-coding Ability Research Articles

ANRIL: A Long Noncoding RNA in Age-related Diseases.

The intensification of the aging population is often accompanied by an increase in agerelated diseases, which impair the quality of life of the elderly. The characteristic feature of aging is progressive physiological decline, which is the largest cause of human pathology and death worldwide. However, natural aging interacts in exceptionally complex ways within and between organs, but its underlying mechanisms are still poorly understood. Long non-coding RNA (lncRNA) is a type of noncoding RNA that exceeds 200 nucleotides in length and does not possess protein-coding ability. It plays a crucial role in the occurrence and development of diseases. ANRIL, also known as CDKN2B-AS1, is an antisense ncRNA located at the INK4 site. It can play a crucial role in agerelated disease progression by regulating single nucleotide polymorphism, histone modifications, or post-transcriptional modifications (such as RNA stability and microRNA), such as cardiovascular disease, diabetes, tumor, arthritis, and osteoporosis. Therefore, a deeper understanding of the molecular mechanisms of lncRNA ANRIL in age-related diseases will help provide new diagnostic and therapeutic targets for clinical practice.

A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway

BackgroundClear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer with high aggressive phenotype and poor prognosis. Accumulating evidence suggests that circRNAs have been identified as pivotal mediators in cancers. However, the role of circRNAs in ccRCC progression remains elusive.MethodsThe differentially expressed circRNAs in 4 paired human ccRCC and adjacent noncancerous tissues ccRCC were screened using circRNA microarrays and the candidate target was selected based on circRNA expression level using weighted gene correlation network analysis (WGCNA) and the gene expression omnibus (GEO) database. CircPDHK1 expression in ccRCC and adjacent noncancerous tissues (n = 148) were evaluated along with clinically relevant information. RT-qPCR, RNase R digestion, and actinomycin D (ActD) stability test were conducted to identify the characteristics of circPDHK1. The subcellular distribution of circPDHK1 was analyzed by subcellular fractionation assay and fluorescence in situ hybridization (FISH). Immunoprecipitation-mass spectrometry (IP-MS) and immunofluorescence (IF) were employed to evaluate the protein-coding ability of circPDHK1. ccRCC cells were transfected with siRNAs, plasmids or lentivirus approach, and cell proliferation, migration and invasion, as well as tumorigenesis and metastasis in nude mice were assessed to clarify the functional roles of circPDHK1 and its encoded peptide PDHK1-241aa. RNA-sequencing, western blot analysis, immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) assays were further employed to identify the underlying mechanisms regulated by PDHK1-241aa.ResultsCircPDHK1 was upregulated in ccRCC tissues and closely related to WHO/ISUP stage, T stage, distant metastasis, VHL mutation and Ki-67 levels. CircPDHK1 had a functional internal ribosome entry site (IRES) and encoded a novel peptide PDHK1-241aa. Functionally, we confirmed that PDHK1-241aa and not the circPDHK1 promoted the proliferation, migration and invasion of ccRCC. Mechanistically, circPDHK1 was activated by HIF-2A at the transcriptional level. PDHK1-241aa was upregulated and interacted with PPP1CA, causing the relocation of PPP1CA to the nucleus. This thereby inhibited AKT dephosphorylation and activated the AKT-mTOR signaling pathway.ConclusionsOur data indicated that circPDHK1-encoded PDHK1-241aa promotes ccRCC progression by interacting with PPP1CA to inhibit AKT dephosphorylation. This study provides novel insights into the multiplicity of circRNAs and highlights the potential use of circPDHK1 or PDHK1-241aa as a therapeutic target for ccRCC.

CircMORC3-encoded novel protein negatively regulates antiviral immunity through synergizing with host gene MORC3.

The protein-coding ability of circRNAs has recently been a hot topic, but the role of protein-coding circRNAs in antiviral innate immunity of teleost fish has rarely been reported. Here, we identified a novel circRNA, termed circMORC3, derived from Microrchidia 3 (MORC3) gene in Miichthys miiuy. circMORC3 can inhibit the expression of antiviral cytokines. In addition, circMORC3 encodes a novel peptide with a length of 84 amino acids termed MORC3-84aa. MORC3-84aa not only significantly inhibited TRIF-mediated activation of IRF3 and NF-κB signaling pathways, but also effectively suppressed the expression of antiviral cytokines triggered by RNA virus Siniperca chuatsi rhabdovirus (SCRV). We found that MORC3-84aa directly interacted with TRIF and negatively regulated TRIF protein expression. In addition, host gene MORC3 attenuates SCRV-induced IFN and ISG expression. Mechanistically, MORC3-84aa promotes autophagic degradation of TRIF by enhancing K6-linked ubiquitination and inhibits TRIF-mediated activation of the type I interferon signaling pathway. And the host gene MORC3 not only repressed IRF3 protein expression but also inhibited IRF3 phosphorylation levels. Our study shows that circMORC3 and host gene MORC3 played a synergistic role in viral immune escape.

A novel protein encoded by circKANSL1L regulates skeletal myogenesis via the Akt-FoxO3 signaling axis

Skeletal muscle is one the largest organs of the body and is involved in animal production and human health. Circular RNAs (circRNAs) have been implicated in skeletal myogenesis through largely unknown mechanisms. Herein, we report the phenotypic and metabolomic analysis of porcine longissimus dorsi muscles in Lantang and Landrace piglets, revealing a high-content of slow-oxidative fibers responsible for high-quality meat product in Lantang piglets. Using single-cell transcriptomics, we identified four myogenesis-related cell types, and the Akt-FoxO3 signaling axis was the most significantly enriched pathway in each subpopulation in the different pig breeds, as well as in fast-twitch glycolytic fibers. Using the multi-dimensional bioinformatic tools of circRNAome-seq and Ribo-seq, we identified a novel circRNA, circKANSL1L, with a protein-coding ability in porcine muscles, whose expression level correlated with myoblast proliferation and differentiation in vitro, as well as the transformation between distinct mature myofibers in vivo. The protein product of circKANSL1L could interact with Akt to decrease the phosphorylation level of FoxO3, which subsequently promoted FoxO3 transcriptional activity to regulate skeletal myogenesis. Our results established the existence of a protein encoded by circKANSL1L and demonstrated its potential functions in myogenesis.

A novel protein encoded by circVPS13D attenuates antiviral innate immunity by targeting MAVS in teleost fish.

The expression of circVPS13D was upregulated with SCRV invasion, which proved that circVPS13D was involved in the regulation of the antiviral immune response. Our study revealed that the existence of circVPS13D promoted the replication of SCRV. Functionally, circVPS13D negatively regulates the antiviral responses of fish. Mechanistically, we confirmed that circVPS13D inhibited RLRs antiviral signaling pathway via the encoded protein VPS13D-170aa by targeting MAVS. Our study provided novel insights into the roles of protein-coding circRNAs and supported VPS13D-170aa as a negative regulator in the antiviral immune responses of teleost fish.

Non-Coding RNA in Cholangiocarcinoma: An Update.

Cholangiocarcinoma (CCA) is one of the most common tumors with high malignancy. Its incidence is increasing year by year, and it is insidious and easily metastasized, and most patients are already in advanced stages when they are diagnosed. Surgery is an essential treatment for CCA, but the 5-year survival rate is still unsatisfactory due to the low early diagnosis rate and high malignancy of CCA. Therefore, exploring the molecular mechanisms of CCA to find reliable biomarkers and effective therapeutic targets is essential to improve the early diagnosis and survival rate of CCA. Non-coding RNA (ncRNA) is a class of RNA without protein-coding ability, mainly including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). In recent years, numerous pieces of evidence have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA through various mechanisms such as mediating epigenetic, sponge miRNAs regulating the expression of target genes and participating in regulating cancer-related signaling pathways, which provides new approaches and ideas for early diagnosis, prognosis assessment and therapeutic targeting of CCA. In this paper, we review the molecular mechanisms of lncRNAs and circRNAs regulating the progression of CCA in recent years and discuss their potential clinical value in CCA.

Circular RNAs with protein-coding ability in oncogenesis.

As ubiquitously expressed transcripts in eukaryotes, circular RNAs (circRNAs) are covalently closed and lack a 5'-cap and 3'-polyadenylation (poly (A)) tail. Initially, circRNAs were considered non-coding RNA (ncRNA), and their roles as sponging molecules to adsorb microRNAs have been extensively reported. However, in recent years, accumulating evidence has demonstrated that circRNAs could encode functional polypeptides through the initiation of translation mediated by internal ribosomal entry sites (IRESs) or N6-methyladenosine (m6A). In this review, we collectively discuss the biogenesis, cognate mRNA products, regulatory mechanisms, aberrant expression and biological phenotypes or clinical relevance of all currently reported, cancer-relevant protein-coding circRNAs. Overall, we provide a comprehensive overview of circRNA-encoded proteins and their physiological and pathological functions.

A novel protein encoded by circUBE4B promotes progression of esophageal squamous cell carcinoma by augmenting MAPK/ERK signaling

Esophageal squamous carcinoma (ESCC) is a common malignant cancer. Although the non-coding roles of circRNAs in the pathogenesis of human tumors have been well studied, whether circRNAs participate in the progression of ESCC by encoding novel proteins remains unclear. In this study, we identified an overexpression circRNA with protein-coding ability in ESCC tissues, called circUBE4B, whose expression level is correlated with tumor size and tumor differentiation level of ESCC patients. Moreover, a higher level of circUBE4B in ESCC patients is correlated with a worse prognosis. Functionally, we found that circUBE4B promoted the proliferation of ESCC cells by encoding a novel cancer-promoting protein, circUBE4B-173aa. Mechanistically, the circUBE4B-173aa protein interacts with MAPK1 and promotes the phosphorylation level of MAPK1 to eventually activate MAPK/ERK signaling pathway. The xenograft model revealed that overexpression of circUBE4B-173aa in ESCC cells significantly promoted the growth of grafts. Our study provides new insights into the mechanism of circRNA in the development of ESCC and circUBE4B-173aa has the potential to serve as a biomarker and a novel therapeutic target for ESCC therapy.

Mining glycosylation-related prognostic lncRNAs and constructing a prognostic model for overall survival prediction in glioma: A study based on bioinformatics analysis.

Dysregulation of protein glycosylation plays a crucial role in the development of glioma. Long noncoding RNA (lncRNAs), functional RNA molecules without protein-coding ability, regulate gene expression and participate in malignant glioma progression. However, it remains unclear how lncRNAs are involved in glycosylation glioma malignancy. Identification of prognostic glycosylation-related lncRNAs in gliomas is necessary. We collected RNA-seq data and clinicopathological information of glioma patients from the cancer genome atlas and Chinese glioma genome atlas. We used the "limma" package to explore glycosylation-related gene and screened related lncRNAs from abnormally glycosylated genes. Using univariate Cox analyses Regression and least absolute shrinkage and selection operator analyses, we constructed a risk signature with 7 glycosylation-related lncRNAs. Based on the median risk score (RS), patients with gliomas were divided into low- and high-risk subgroups with different overall survival rates. Univariate and multivariate Cox analyses regression analyses were performed to assess the independent prognostic ability of the RS. Twenty glycosylation-related lncRNAs were identified by univariate Cox regression analyses. Two glioma subgroups were identified using consistent protein clustering, with the prognosis of the former being better than that of the latter. Least absolute shrinkage and selection operator analysis identified 7 survival RSs for glycosylation-related lncRNAs, which were identified as independent prognostic markers and predictors of glioma clinicopathological features. Glycosylation-related lncRNAs play an important role in the malignant development of gliomas and may help guide treatment options.

Abstract 3809: Differential regulation of novel long non coding RNAs and their mechanism of action in p73 dependent manner

Abstract The p53 tumor suppressor family is classically activated after DNA damage and plays a central role in cell fate decisions. Although, the p53 family activates many of the same genes in response to DNA damage, p73 plays distinct biological functions in development and metastasis. It is likely that p73 activates a unique transcriptional network which is critical for its anti-metastatic and anti-invasive action. Long non-coding RNAs (lncRNAs) are a class of mRNA- like transcripts longer than 200 nucleotides. They lack protein-coding ability and are believed to be involved in various kinds of biological processes. Increasing evidence suggests that lncRNA are frequently aberrantly expressed in cancers. Therefore, the roles of dysregulated functional lncRNA in human malignant tumors have attracted considerable scientific interest. The objective of our study is to find out novel long non-coding RNAs that can act as transcriptional targets of p73 and to delineate their role in p73-mediated anti-metastatic response. For this purpose, we performed transcriptome sequencing in HCT116p73wt and HCT116p73KD cells and screened the data for modulation of expression of lncRNAs in differential manner. Quantitative Real Time PCR was further carried out to validate the data obtained after screening RNA seq Data. Promoter analysis was carried out for the identification of p73 binding sites in the selected upregulated or downregulated lncRNAs which was further confirmed by Luciferase reporter, ChIP and site directed mutagenesis assays. About six lncRNAs were observed to be significantly upregulated while four were down-regulated upon knockdown of p73. The promoters of selected lncRNAs were analysed in silico using TF Bind and JASPAR software for p73 binding sites and luciferase reporter assays suggested regulation of lncRNAs by p73. Chromatin immunoprecipitation showed promoter enrichment of the selected lncRNAs. Together, our study provides insights into the differential regulation of long non- coding RNAs in p73 dependent manner which further will provide the mechanism of their action at the genome level. Citation Format: Chanchal Bareja, Apoorva Uboveja, Daman Saluja. Differential regulation of novel long non coding RNAs and their mechanism of action in p73 dependent manner. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3809.

The tumor therapeutic potential of long non-coding RNA delivery and targeting.

Long non-coding RNAs (lncRNAs) is a type of RNA over 200nt long without any protein coding ability, which has been investigated relating to crucial biological function in cells. There are many key lncRNAs in tumor/normal cells that serve as a biological marker or a new target for tumor treatment. However, compared to some small non-coding RNA, lncRNA-based drugs are limited in clinical application. Different from other non-coding RNA, like microRNAs, most lncRNAs have a high molecular weight and conserved secondary structure, making the delivery of lncRNAs more complex than the small non-coding RNAs. Considering that lncRNAs constitute the most abundant part of the mammalian genome, it is critical to further explore lncRNA delivery and the subsequent functional studies for potential clinical application. In this review, we will discuss the function and mechanism of lncRNAs in diseases, especially cancer, and different approaches for lncRNA transfection using multiple biomaterials.

Bta-miR-206 and a Novel lncRNA-lncA2B1 Promote Myogenesis of Skeletal Muscle Satellite Cells via Common Binding Protein HNRNPA2B1.

Skeletal muscle satellite cells (MuSCs) can proliferate, differentiate, and self-renew, and can also participate in muscle formation and muscle injury repair. Long noncoding RNAs (lncRNAs) can play an important role with the RNA binding protein and microRNAs (miRNAs) to regulate the myogenesis of bovine MuSCs, however, its molecular mechanism is still being explored. In this study, differentially expressed 301 lncRNAs were identified during the myogenic differentiation of cells based on an in vitro model of induced differentiation of bovine MuSCs using RNA sequencing (RNA-seq). Based on the ability of miR-206 to regulate myogenic cell differentiation, a new kind of lncRNA-lncA2B1 without protein-coding ability was found, which is expressed in the nucleus and cytoplasm. Subsequently, lncA2B1 inhibited cell proliferation by downregulating the expression of the proliferation marker Pax7 and promoted myogenic differentiation by upregulating the expression of the differentiation marker MyHC, whose regulatory function is closely related to miR-206. By RNA pulldown/LC-MS experiments, heterogeneous ribonucleoprotein A2/B1 (HNRNPA2B1), and DExH-Box Helicase 9 (DHX9) were identified as common binding proteins of lncA2B1 and miR-206. Overexpression of lncA2B1 and miR-206 significantly upregulated the expression level of HNRNPA2B1. Downregulation of HNRNPA2B1 expression significantly decreased the expression level of the differentiation marker MyHC, which indicates that miR-206 and lncA2B1 regulate myogenic differentiation of bovine MuSCs by acting on HNRNPA2B1. This study screened and identified a novel lncRNA-lncA2B1, which functions with miR-206 to regulate myogenesis via the common binding proteins HNRNPA2B1. The results of this study provide a new way to explore the molecular mechanisms by which lncRNAs and miRNAs regulate muscle growth and development.

Long Non-Coding RNA lncWOX11a Suppresses Adventitious Root Formation of Poplar by Regulating the Expression of PeWOX11a.

Long non-coding RNAs (lncRNAs), a class of poorly conserved transcripts without protein-encoding ability, are widely involved in plant organogenesis and stress responses by mediating the transmission and expression of genetic information at the transcriptional, posttranscriptional, and epigenetic levels. Here, we cloned and characterized a novel lncRNA molecule through sequence alignment, Sanger sequencing, transient expression in protoplasts, and genetic transformation in poplar. lncWOX11a is a 215 bp transcript located on poplar chromosome 13, ~50 kbp upstream of PeWOX11a on the reverse strand, and the lncRNA may fold into a series of complex stem-loop structures. Despite the small open reading frame (sORF) of 51 bp within lncWOX11a, bioinformatics analysis and protoplast transfection revealed that lncWOX11a has no protein-coding ability. The overexpression of lncWOX11a led to a decrease in the quantity of adventitious roots on the cuttings of transgenic poplars. Further, cis-regulatory module prediction and CRISPR/Cas9 knockout experiments with poplar protoplasts demonstrated that lncWOX11a acts as a negative regulator of adventitious rooting by downregulating the WUSCHEL-related homeobox gene WOX11, which is supposed to activate adventitious root development in plants. Collectively, our findings imply that lncWOX11a is essential for modulating the formation and development of adventitious roots.

Circularized RNA as novel therapeutics in cancer.

Circular RNAs (CircRNAs) regulate gene expression by functioning as microRNA sponges, regulating protein stability, and gilding proteins for gene transcription and translation. Also, limited circRNAs harbour protein-coding ability through cap-independent pathways. These molecular mechanisms of circRNAs contribute to their importance in several cellular processes. Particularly, the dysregulation of circRNAs also plays a critical role in disease development. Targeting disease-causing circRNAs by restoring their normal expression by gain-of-function or loss-of-function approach and regulating their molecular activities could be potential direction for the development of anti-cancer therapies. Furthermore, due to unique covalently closed circular structure, the superior stability of circRNAs also grants them as novel therapeutic tools replacing the therapeutic small interfering RNAs and messenger RNAs. Here, we will review the functional and molecular mechanisms of circRNAs in pathogenesis, the current methods for targeting the dysregulated circRNAs, and the potential of using synthetic circRNAs in disease treatment and prevention.

Investigating nicotine pathway-related long non-coding RNAs in tobacco.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200bp with low or no protein-coding ability, which play essential roles in various biological processes in plants. Tobacco is an ideal model plant for studying nicotine biosynthesis and metabolism, and there is little research on lncRNAs in this field. Therefore, how to take advantage of the mature tobacco system to profoundly investigate the lncRNAs involved in the nicotine pathway is intriguing. By exploiting 549 public RNA-Seq datasets of tobacco, 30,212 lncRNA candidates were identified, including 24,084 large intervening non-coding RNAs (lincRNAs), 5,778 natural antisense transcripts (NATs) and 350 intronic non-coding RNAs (incRNAs). Compared with protein-coding genes, lncRNAs have distinct properties in terms of exon number, sequence length, A/U content, and tissue-specific expression pattern. lincRNAs showed an asymmetric evolutionary pattern, with a higher proportion (68.71%) expressed from the Nicotiana sylvestris (S) subgenome. We predicted the potential cis/trans-regulatory effects on protein-coding genes. One hundred four lncRNAs were detected as precursors of 30 known microRNA (miRNA) family members, and 110 lncRNAs were expected to be the potential endogenous target mimics for 39 miRNAs. By combining the results of weighted gene co-expression network analysis with the differentially expressed gene analysis of topping RNA-seq data, we constructed a sub-network containing eight lncRNAs and 25 nicotine-related coding genes. We confirmed that the expression of seven lncRNAs could be affected by MeJA treatment and may be controlled by the transcription factor NtMYC2 using a quantitative PCR assay and gene editing. The results suggested that lncRNAs are involved in the nicotine pathway. Our findings further deepened the understanding of the features and functions of lncRNAs and provided new candidates for regulating nicotine biosynthesis in tobacco.

Investigating SH-SY5Y Neuroblastoma Cell Surfaceome as a Model for Neuronal-Targeted Novel Therapeutic Modalities

The SH-SY5Y neuroblastoma cells are a widely used in vitro model approximating neurons for testing the target engagement of therapeutics designed for neurodegenerative diseases and pain disorders. However, their potential as a model for receptor-mediated delivery and uptake of novel modalities, such as antibody-drug conjugates, remains understudied. Investigation of the SH-SY5Y cell surfaceome will aid in greater in vitro to in vivo correlation of delivery and uptake, thereby accelerating drug discovery. So far, the majority of studies have focused on total cell proteomics from undifferentiated and differentiated SH-SY5Y cells. While some studies have investigated the expression of specific proteins in neuroblastoma tissue, a global approach for comparison of neuroblastoma cell surfaceome to the brain and dorsal root ganglion (DRG) neurons remains uninvestigated. Furthermore, an isoform-specific evaluation of cell surface proteins expressed on neuroblastoma cells remains unexplored. In this study, we define a bioinformatic workflow for the identification of high-confidence surface proteins expressed on brain and DRG neurons using tissue proteomic and transcriptomic data. We then delineate the SH-SY5Y cell surfaceome by surface proteomics and show that it significantly overlaps with the human brain and DRG neuronal surface proteome. We find that, for 32% of common surface proteins, SH-SY5Y-specific major isoforms are alternatively spliced, maintaining their protein-coding ability, and are predicted to localize to the cell surface. Validation of these isoforms using surface proteomics confirms a SH-SY5Y-specific alternative NRCAM (neuron-glia related cell adhesion molecule) isoform, which is absent in typical brain neurons, but present in neuroblastomas, making it a receptor of interest for neuroblastoma-specific therapeutics.

Long Intergenic Non-Protein Coding RNA 173 in Human Cancers

Long non-coding RNAs belong to non-coding RNAs (ncRNAs) with a length of more than 200 nucleotides and limited protein-coding ability. Growing research has clarified that dysregulated lncRNAs are correlated with the development of various complex diseases, including cancer. LINC00173 has drawn researchers' attention as one of the recently discovered lncRNAs. Aberrant expression of LINC00173 affects the initiation and progression of human cancers. In the present review, we summarize the recent considerable research on LINC00173 in 11 human cancers. Through the summary of the abnormal expression of LINC00173 and its potential molecular regulation mechanism in cancers, this article indicates that LINC00173 may serve as a potential diagnostic biomarker and a target for drug therapy, thus providing novel clues for future related research.

Exosome-encapsulated ncRNAs: Emerging yin and yang of tumor hallmarks.

Tumorigenesis is a multifaceted process, where multiple physiological traits serving as cancer's distinctive characteristics are acquired. "Hallmarks of cancer" is a set of cognitive abilities acquired by human cells that are pivotal to their tumor-forming potential. With limited or no protein-coding ability, non-coding RNAs (ncRNAs) interact with their target molecules and yield significant regulatory effects on several cell cycle processes. They play a "yin" and "yang" role, thereby functioning both as oncogenic and tumor suppressor and considered important in the management of various types of cancer entities. ncRNAs serve as important post-transcriptional and translational regulators of not only unrestricted expansion and metastasis of tumor cells but also of various biological processes, such as genomic mutation, DNA damage, immune escape, and metabolic disorder. Dynamical attributes such as increased proliferative signaling, migration, invasion, and epithelial-mesenchymal transition are considered to be significant determinants of tumor malignancy, metastatic dissemination, and therapeutic resistance. Furthermore, these biological attributes engage tumor cells with immune cells within the tumor microenvironment to promote tumor formation. We elaborate the interaction of ncRNAs with various factors in order to regulate cancer intra/intercellular signaling in a specific tumor microenvironment, which facilitates the cancer cells in acquiring malignant hallmarks. Exosomes represent a means of intercellular communication and participate in the maintenance of the tumor hallmarks, adding depth to the intricate, multifactorial character of malignant neoplasia. To summarize, ncRNAs have a profound impact on tumors, affecting their microcirculation, invasiveness, altered metabolism, microenvironment, and the capacity to modify the host immunological environment. Though the significance of ncRNAs in crosstalk between the tumor and its microenvironment is being extensively explored, we intend to review the hallmarks in the light of exosome-derived non-coding RNAs and their impact on the tumor microenvironment.

Crosstalk among long non-coding RNA, tumor-associated macrophages and small extracellular vesicles in tumorigenesis and dissemination.

Long noncoding RNAs (lncRNAs), which lack protein-coding ability, can regulate cancer cell growth, proliferation, invasion, and metastasis. Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment that have a significant impact on cancer progression. Small extracellular vesicles (sEV) are crucial mediators of intercellular communications. Cancer cell and macrophage-derived sEV can carry lncRNAs that influence the onset and progression of cancer. Dysregulation of lncRNAs, TAMs, and sEV is widely observed in tumors which makes them valuable targets for cancer immunotherapy. In this review, we summarize current updates on the interactions among sEV, lncRNAs, and TAMs in tumors and provide new perspectives on cancer diagnosis and treatment.

Emerging Role of Non-Coding RNAs in Aortic Dissection.

Aortic dissection (AD) is a fatal cardiovascular acute disease with high incidence and mortality, and it seriously threatens patients’ lives and health. The pathogenesis of AD mainly includes vascular inflammation, extracellular matrix degradation, and phenotypic conversion as well as apoptosis of vascular smooth muscle cells (VSMCs); however, its detailed mechanisms are still not fully elucidated. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are an emerging class of RNA molecules without protein-coding ability, and they play crucial roles in the progression of many diseases, including AD. A growing number of studies have shown that the dysregulation of ncRNAs contributes to the occurrence and development of AD by modulating the expression of specific target genes or the activity of related proteins. In addition, some ncRNAs exhibit great potential as promising biomarkers and therapeutic targets in AD treatment. In this review, we systematically summarize the recent findings on the underlying mechanism of ncRNA involved in AD regulation and highlight their clinical application as biomarkers and therapeutic targets in AD treatment. The information reviewed here will be of great benefit to the development of ncRNA-based therapeutic strategies for AD patients.