Protein-coding Function Research Articles

Non-coding RNAs in Tumor Biology: Exploring miRNAs, lncRNAs, and circRNAs Roles and Therapeutic Potentials

Tumorigenesis and progression are complex process with multifarious molecules and related mechanisms, while most of them are still elusive. Most research into the mechanisms of cancer today are focusing on encoding RNAs. However, for the past few years as the emergence and development of epigenetics, a kind of new molecule: non-coding RNAs (ncRNAs), RNAs without protein-coding function, have gained prominence in recent scientific discussions. Since the first ncRNA was discovered in 1990s, extensive research has shown that ncRNAs significantly influence processes such as cell growth, differentiation, metabolic regulation, and programmed cell death at both transcriptional and post-transcriptional stages. By means of acting as the tumor suppression and oncogenesis, research has identified several ncRNAs with abnormal expression patterns in cancer cells, marking them as primary oncogenic factors or valuable targets in cancer treatment. This review focus on three kinds of ncRNA, MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), the molecule structure, generative mechanism, characteristic function and regulatory mechanism in tumor progression. In addition, we will discuss the application value and future expiration of the therapeutic that are focusing on ncRNA, that will open up a new idea and methods for the treatment of cancer for future investigation.

Representation of non-coding RNA-mediated regulation of gene expression using the Gene Ontology

ABSTRACT Regulatory non-coding RNAs (ncRNAs) are increasingly recognized as integral to the control of biological processes. This is often through the targeted regulation of mRNA expression, but this is by no means the only mechanism through which regulatory ncRNAs act. The Gene Ontology (GO) has long been used for the systematic annotation of protein-coding and ncRNA gene function, but rapid progress in the understanding of ncRNAs meant that the ontology needed to be revised to accurately reflect current knowledge. Here, a targeted effort to revise GO terms used for the annotation of regulatory ncRNAs is described, focusing on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs). This paper provides guidance to biocurators annotating ncRNA-mediated processes using the GO and serves as background for researchers wishing to make use of the GO in their studies of ncRNAs and the biological processes they regulate.

Relationship between lncRNA MALAT1 and Chemo-radiotherapy Resistance of Cancer Cells: Uncovered Truths.

The advancement of novel technologies, coupled with bioinformatics, has led to the discovery of additional genes, such as long noncoding RNAs (lncRNAs), that are associated with drug resistance. LncRNAs are composed of over 200 nucleotides and do not possess any protein coding function. These lncRNAs exhibit lower conservation across species, are typically expressed at low levels, and often display high specificity towards specific tissues and developmental stages. The LncRNA MALAT1 plays crucial regulatory roles in various aspects of genome function, encompassing gene transcription, splicing, and epigenetics. Additionally, it is involved in biological processes related to the cell cycle, cell differentiation, development, and pluripotency. Recently, MALAT1 has emerged as a novel mechanism contributing to drug resistance or sensitivity, attracting significant attention in the field of cancer research. This review aims to explore the mechanisms through which MALAT1 confers resistance to chemotherapy and radiotherapy in cancer cells.

Role of miRNAs in macrophage-mediated kidney injury.

Macrophages, crucial components of the human immune system, can be polarized into M1/M2 phenotypes, each with distinct functions and roles. Macrophage polarization has been reported to be significantly involved in the inflammation and fibrosis observed in kidney injury. MicroRNA (miRNA), a type of short RNA lacking protein-coding function, can inhibit specific mRNA by partially binding to its target mRNA. The intricate association between miRNAs and macrophages has been attracting increasing interest in recent years. This review discusses the role of miRNAs in regulating macrophage-mediated kidney injury. It shows how miRNAs can influence macrophage polarization, thereby altering the biological function of macrophages in the kidney. Furthermore, this review highlights the significance of miRNAs derived from exosomes and extracellular vesicles as a crucial mediator in the crosstalk between macrophages and kidney cells. The potential of miRNAs as treatment applications and biomarkers for macrophage-mediated kidney injury is also discussed.

M6A modification of lncRNA PHKA1-AS1 enhances Actinin Alpha 4 stability and promotes non-small cell lung cancer metastasis.

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non-small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1-AS1) in the progression of NSCLC were explored. The increased level of N6-methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1-AS1. Subsequently, high-expressed PHKA1-AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1-AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1-AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1-AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

The physical and evolutionary energy landscapes of devolved protein sequences corresponding to pseudogenes

Protein evolution is guided by structural, functional, and dynamical constraints ensuring organismal viability. Pseudogenes are genomic sequences identified in many eukaryotes that lack translational activity due to sequence degradation and thus over time have undergone "devolution." Previously pseudogenized genes sometimes regain their protein-coding function, suggesting they may still encode robust folding energy landscapes despite multiple mutations. We study both the physical folding landscapes of protein sequences corresponding to human pseudogenes using the Associative Memory, Water Mediated, Structure and Energy Model, and the evolutionary energy landscapes obtained using direct coupling analysis (DCA) on their parent protein families. We found that generally mutations that have occurred in pseudogene sequences have disrupted their native global network of stabilizing residue interactions, making it harder for them to fold if they were translated. In some cases, however, energetic frustration has apparently decreased when the functional constraints were removed. We analyzed this unexpected situation for Cyclophilin A, Profilin-1, and Small Ubiquitin-like Modifier 2 Protein. Our analysis reveals that when such mutations in the pseudogene ultimately stabilize folding, at the same time, they likely alter the pseudogenes' former biological activity, as estimated by DCA. We localize most of these stabilizing mutations generally to normally frustrated regions required for binding to other partners.

Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas

Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, independent of its protein-coding function, confers mesenchymal properties to the cell, promoting migration, invasiveness, and resistance to anoikis and increasing glycolytic activity by sequestering miRNAs. Expression of Serpine1 mRNA upregulates the expression of the TRA2B splicing factor without affecting its mRNA levels. Through transcriptional profiling, we found that Serpine1 mRNA expression downregulates through TRA2B the expression of genes involved in the immune response. Analysis of human colon tumor samples showed an inverse correlation between SERPINE1 mRNA expression and CD8+ T cell infiltration, unveiling the potential value of SERPINE1 mRNA as a promising therapeutic target for colon tumors.

Salivaomics to decode non-coding RNAs in oral cancer. A narrative review.

Oral cancer is the most debilitating disease which affects the orderly life of a human. With so much advancement in research and technology, the average life expectancy of an individual with oral cancer appears to be about 5 years. The changing trend in incidence of oral cancer among young individuals and women without tobacco habits are ascending. Non habit related oral cancer are taking centre stage and multiple factors which induce complex biology are associated in such scenarios. To decipher the aetiology and to understand the process, these cancerous conditions are to be studied at molecular level. Saliva, the most non-invasively obtained body fluid are assessed for biomarkers exclusively in liquid biopsy. This fluid gives a huge platform to study number of molecules associated with oral cancer. Non coding RNAs are transcripts with no protein coding function. They are gaining more importance in recent times. Long noncoding RNA, microRNA are major types of noncoding transcriptome that influences in progression of oral cancer. They seem to play an important role in health and disease. Apart from these, circulating tumour cells, exosomes, extracellular vesicles, antigens and other proteins can be studied from saliva. This review is aimed to update the knowledge on current biomarkers in saliva associated with oral cancer and their epigenetic role in disease progression as well recent advances in detecting these markers to identify the stage of the disease, which will help in deciding the treatment protocol.

Gene SH3BGRL3 regulates acute myeloid leukemia progression through circRNA_0010984 based on competitive endogenous RNA mechanism.

Introduction: Acute myeloid leukemia (AML) is a malignant proliferative disease affecting the bone marrow hematopoietic system and has a poor long-term outcome. Exploring genes that affect the malignant proliferation of AML cells can facilitate the accurate diagnosis and treatment of AML. Studies have confirmed that circular RNA (circRNA) is positively correlated with its linear gene expression. Therefore, by exploring the effect of SH3BGRL3 on the malignant proliferation of leukemia, we further studied the role of circRNA produced by its exon cyclization in the occurrence and development of tumors. Methods: Genes with protein-coding function obtained from the TCGA database. we detected the expression of SH3BGRL3 and circRNA_0010984 by real-time quantitative polymerase chain reaction (qRT-PCR). We synthesized plasmid vectors and carried out cell experiments, including cell proliferation, cell cycle and cell differentiation by cell transfection. We also studied the transfection plasmid vector (PLVX-SHRNA2-PURO) combined with a drug (daunorubicin) to observe the therapeutic effect. The miR-375 binding site of circRNA_0010984 was queried using the circinteractome databases, and the relationship was validated by RNA immunoprecipitation and Dual-luciferase reporter assay. Finally, a protein-protein interaction network was constructed with a STRING database. GO and KEGG functional enrichment identified mRNA-related functions and signaling pathways regulated by miR-375. Results: We identified the related gene SH3BGRL3 in AML and explored the circRNA_0010984 produced by its cyclization. It has a certain effect on the disease progression. In addition, we verified the function of circRNA_0010984. We found that circSH3BGRL3 knockdown specifically inhibited the proliferation of AML cell lines and blocked the cell cycle. We then discussed the related molecular biological mechanisms. CircSH3BGRL3 acts as an endogenous sponge for miR-375 to isolate miR-375 and inhibits its activity, increases the expression of its target YAP1, and ultimately activates the Hippo signaling pathway involved in malignant tumor proliferation. Discussion: We found that SH3BGRL3 and circRNA_0010984 are important to AML. circRNA_0010984 was significantly up-regulated in AML and promoted cell proliferation by regulating miR-375 through molecular sponge action.

Molecular Evolution of Interferon-Epsilon (IFNε) Pseudogene Modulates Innate and Specific Antiviral Immunity in Manis javanica

Interferon-Epsilon (IFNε) is a type of interferon, a protein that plays a role in the immune response to viral infections. This study is aimed at examining the molecular evolution of the IFNε pseudogene in Manis javanica, and it has been found to modulate the innate and specific antiviral immunity in this species. In this study, we identified that IFNε gene has undergone rapid evolution in Manis javanica, with the human and primate IFNε genes showing evidence of positive selection. This suggests that IFNε has played an important role in the evolution of the immune system, possibly in response to coevolution with viral pathogens. Comparative genomic analysis revealed that the IFNε pseudogene in pangolins originated from a gene duplication event approximately 48 million years ago. It subsequently lost its protein-coding function due to multiple deleterious mutations. However, the IFNε pseudogene exhibits a high degree of conservation in its promoter region, suggesting it may still play a regulatory role in antiviral immunity. This suggests that the pseudogene may have evolved to serve an important function in the pangolin’s immune system, potentially helping to protect it from viral infections. The molecular evolution of IFNε provides insights into the coevolutionary dynamics between host immune systems and viral pathogens and may have implications for developing new antiviral therapies.

Roles of long non-coding RNAs in plant immunity.

Robust plant immune systems are fine-tuned by both protein-coding genes and non-coding RNAs. Long non-coding RNAs (lncRNAs) refer to RNAs with a length of more than 200 nt and usually do not have protein-coding function and do not belong to any other well-known non-coding RNA types. The non-protein-coding, low expression, and non-conservative characteristics of lncRNAs restrict their recognition. Although studies of lncRNAs in plants are in the early stage, emerging studies have shown that plants employ lncRNAs to regulate plant immunity. Moreover, in response to stresses, numerous lncRNAs are differentially expressed, which manifests the actions of low-expressed lncRNAs and makes plant-microbe/insect interactions a convenient system to study the functions of lncRNAs. Here, we summarize the current advances in plant lncRNAs, discuss their regulatory effects in different stages of plant immunity, and highlight their roles in diverse plant-microbe/insect interactions. These insights will not only strengthen our understanding of the roles and actions of lncRNAs in plant-microbe/insect interactions but also provide novel insight into plant immune responses and a basis for further research in this field.

Expression and molecular regulation of non-coding RNAs in HPV-positive head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide. Accumulating evidence suggests that persistent HPV infection is closely related to a subset of HNSCC types, and the incidence of human papillomavirus (HPV)-positive HNSCC has been annually increasing in recent decades. Although the carcinogenesis of HPV-positive HNSCC has not been completely elucidated, it has been well confirmed that E6 and E7, the main viral oncoproteins are responsible for the maintenance of malignant transformation, promotion of cell proliferation, and increase in tumor invasion. Moreover, compared with HPV-negative HNSCC, HPV-positive HNSCC shows some special clinical-pathological features, which are possibly related to HPV infection and their specific regulatory mechanisms. Non-coding RNA (ncRNA) is a class of RNA lacking the protein-coding function and playing a critical regulatory role via multiple complex molecular mechanisms. NcRNA is an important regulatory pattern of epigenetic modification, which can exert significant effects on HPV-induced tumorigenesis and progression by deregulating downstream genes. However, the knowledge of ncRNAs is still limited, hence, a better understanding of ncRNAs could provide some insights for exploring the carcinogenesis mechanism and identifying valuable biomarkers in HPV-positive HNSCC. Therefore, in this review, we mainly focused on the expression profile of ncRNAs (including lncRNA, miRNA, and circRNA) and explored their regulatory role in HPV-positive HNSCC, aiming to clarify the regulatory mechanism of ncRNAs and identify valuable biomarkers for HPV-positive HNSCC.

Construction of a pyroptosis-related lncRNAs signature for predicting prognosis and immunotherapy response in glioma.

Recent studies have proved that pyroptosis-related long non-coding RNAs (PRlncRNAs) are closely linked to tumor progression, prognosis, and immunity. Here, we systematically evaluated the correlation of PRlncRNAs with glioma prognosis. This study included 3 glioma cohorts (The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Gravendeel). Through Pearson correlation analysis, PRlncRNAs were screened from these 3 cohorts. Univariate Cox regression analysis was then carried out to determine the prognostic PRlncRNAs. A pyroptosis-related lncRNAs signature (PRLS) was then built by least absolute shrinkage and selection operator and multivariate Cox analyses. We systematically evaluated the correlation of the PRLS with the prognosis, immune features, and tumor mutation burden in glioma. A total of 14 prognostic PRlncRNAs overlapped in all cohorts and were selected as candidate lncRNAs. Based on The Cancer Genome Atlas cohort, a PRLS containing 7 PRlncRNAs was built. In all cohorts, the PRLS was proved to be a good predictor of glioma prognosis, with a higher risk score related to a poorer prognosis. We observed obvious differences in the immune microenvironment, immune cell infiltration level, and immune checkpoint expression in low- and high-risk subgroups. Compared with low-risk cases, high-risk cases had lower Tumor Immune Dysfunction and Exclusion scores and greater tumor mutation burden, indicating that high-risk cases can be more sensitive to immunotherapy. A nomogram combining PRLS and clinical parameters was constructed, which showed more robust and accurate predictive power. In conclusion, the PRLS is a potentially useful indicator for predicting prognosis and response to immunotherapy in glioma. Our findings may provide a useful insight into clinically individualized treatment strategies for patients.

Mutation of gdpS gene induces a viable but non-culturable state in Staphylococcus epidermidis and changes in the global transcriptional profile

BackgroundIn the genome of staphylococci, only the gdpS gene encodes the conserved GGDEF domain, which is the characteristic of diguanylate cyclases. In our previous study, we have demonstrated that the gdpS gene can modulate biofilm formation by positively regulating the expression of ica operon in Staphylococcus epidermidis. Moreover, this regulation seems to be independent of the c-di-GMP signaling pathway and the protein-coding function of this gene. Therefore, the biological function of the gdpS gene remains to be further investigated.ResultsIn the present study, it was observed that mutation of the gdpS gene induced S. epidermidis to enter into a presumed viable but nonculturable state (VBNC) after cryopreservation with glycerol. Similarly, when moved from liquid to solid culture medium, the gdpS mutant strain also exhibited a VBNC state. Compared with the wild-type strain, the gdpS mutant strain autolyzed more quickly during storage at 4℃, indicating its increased susceptibility to low temperature. Transcriptional profiling analysis showed that the gdpS mutation affected the transcription of 188 genes (92 genes were upregulated and 96 genes were downregulated). Specifically, genes responsible for glycerol metabolism were most markedly upregulated and most of the altered genes in the mutant strain are those involved in nitrogen metabolism. In addition, the most significantly downregulated genes included the betB gene, whose product catalyzes the synthesis of glycine betaine and confers tolerance to cold.ConclusionThe preliminary results suggest that the gdpS gene may participate in VBNC formation of S. epidermidis in face of adverse environmental factors, which is probably achieved by regulating expression of energy metabolism genes. Besides, the gdpS gene is critical for S. epidermidis to survive low temperature, and the underlying mechanism may be partly explained by its influence on expression of betB gene.

Bone Marrow Mesenchymal Stem Cells (BMSCs)-Triggered Up-Regulation of miR-198 Impedes the Aggressive Migration and Invasion of Cervical Cancer Cells

As a subset of RNAs without protein-coding function, short non-coding RNAs (microRNAs) are reported to contribute to the progress of multiple disorders. Nevertheless, the precise function of miR-198 in human cervical cancer is still an open question. RNA sequencing between cervical cancer cell lines and normal cervical epithelial cells identified CCAR1 to be highly expressed in cervical cancer. Cells were transfected with si-CCAR1 followed by analysis of cell behaviors using clonogenic assay and transwell migrating assay. The binding of miR-198 and CCAR1 was verified by a dual-luciferase reporter gene experiment. CCAR1 was highly expressed in cervical cancer tissues and cell lines and associated with tumor staging. Knockdown of CCAR1 restrained the malignant phenotypes of cervical cancer cells. CCAR1 was a target of miR198. Co-culture with BMSCs upregulated miR-198 expression, resulting in impediment of the aggressive phenotypes of cervical cancer cells, which was mediated by suppression of CCAR1 and release of inflammatory factors. In conclusion, CCAR1 level is increased in cervical cancer tissues or cell lines. Co-culture of BMSCs can facilitate the proliferating, migrating and invading activities of cervical cancer cells but reduce the release of inflammatory factors which is possibly through manipulating the axis of miR-198/CCAR1.

Regulation of Oxidative Stress by Long Non-coding RNAs in Central Nervous System Disorders.

Central nervous system (CNS) disorders, such as ischemic stroke, Alzheimer’s disease, Parkinson’s disease, spinal cord injury, glioma, and epilepsy, involve oxidative stress and neuronal apoptosis, often leading to long-term disability or death. Emerging studies suggest that oxidative stress may induce epigenetic modifications that contribute to CNS disorders. Non-coding RNAs are epigenetic regulators involved in CNS disorders and have attracted extensive attention. Long non-coding RNAs (lncRNAs) are non-coding RNAs more than 200 nucleotides long and have no protein-coding function. However, these molecules exert regulatory functions at the transcriptional, post-transcriptional, and epigenetic levels. However, the major role of lncRNAs in the pathophysiology of CNS disorders, especially related to oxidative stress, remains unclear. Here, we review the molecular functions of lncRNAs in oxidative stress and highlight lncRNAs that exert positive or negative roles in oxidation/antioxidant systems. This review provides novel insights into the therapeutic potential of lncRNAs that mediate oxidative stress in CNS disorders.

The Biological and Molecular Function of LINC00665 in Human Cancers.

Long non-coding RNAs (lncRNAs) are more than 200 nucleotides in length and are implicated in the development of human cancers, without protein-coding function. Mounting evidence indicates that cancer initiation and progression are triggered by lncRNA dysregulation. Recently, a growing number of studies have found that LINC00665, a long intergenic non-protein coding RNA, may be associated with various cancers, including gastrointestinal tumors, gynecological tumors, and respiratory neoplasms. LINC00665 was reported to be significantly dysregulated in cancers and has an important clinical association. It participates in cell proliferation, migration, invasion, and apoptosis through different biological pathways. In this review, we summarize the current findings on LINC00665, including its biological roles and molecular mechanisms in various cancers. LINC00665 may be a potential prognostic biomarker and novel therapeutic target for cancers.

Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression.

Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.

CircSLC41A1 Resists Porcine Granulosa Cell Apoptosis and Follicular Atresia by Promoting SRSF1 through miR-9820-5p Sponging.

Ovarian granulosa cell (GC) apoptosis is the major cause of follicular atresia. Regulation of non-coding RNAs (ncRNAs) was proved to be involved in regulatory mechanisms of GC apoptosis. circRNAs have been recognized to play important roles in cellular activity. However, the regulatory network of circRNAs in follicular atresia has not been fully validated. In this study, we report a new circRNA, circSLC41A1, which has higher expression in healthy follicles compared to atretic follicles, and confirm its circular structure using RNase R treatment. The resistant function of circSLC41A1 during GC apoptosis was detected by si-RNA transfection and the competitive binding of miR-9820-5p by circSLC41A1 and SRSF1 was detected with a dual-luciferase reporter assay and co-transfection of their inhibitors or siRNA. Additionally, we predicted the protein-coding potential of circSLC41A1 and analyzed the structure of circSLC41A1-134aa. Our study revealed that circSLC41A1 enhanced SRSF1 expression through competitive binding of miR-9820-5p and demonstrated a circSLC41A1–miR-9820-5p–SRSF1 regulatory axis in follicular GC apoptosis. The study adds to knowledge of the post-transcriptional regulation of follicular atresia and provides insight into the protein-coding function of circRNA.

Akut Myokard Enfarktüsü için Potansiyel Yeni Bir Biyobelirteç Olarak Dolaşan Uzun İntergenik Kodlamayan RNA LINC01538: Prospektif Kohort Çalışma

Objective: Non-coding RNAs are the RNAs with no protein coding function, long non-coding RNAs (LncRNAs) are the non-coding RNAs with more than 200 nucleotides. During the journey of discovering novel biomarkers for diagnosis of myocardial infarction (MI), the principle of studying the LncRNA as a potential would be always attractive, as it needs easy sample collection, has high detection sensitivity and high myocardial tissue specificity. Our main objective was to investigate the potential of LINC01538 as a novel diagnostic biomarker for MI. Material and Methods: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to assess the expression of the serum LINC01538 in 50 ST Elevation MI (STEMI) patients and 48 controls. Results: The study showed a significant increase in serum level expression of LINC01538 in MI patients compared to controls [12 (6.6- 21.8) vs. 0.07 (0.01-0.2), p<0.001]. LINC01538 expression level in MI group was positively correlated with creatine kinase MB and high sensitive cardiac troponin I (hs-cTnI) (r=0.39, p=0.006 and r=0.22, p=0.007, respectively). Hs-cTnI found to have diagnostic value for MI with an area under curve (AUC) 0.917 [95% confidence interval (CI): 0.855- 0.979, p<0.001] at an optimal cutoff point of 1.45 ng/L, 90% sensitivity and 91% specificity. However, LINC01538 showed the highest diagnostic value with an AUC 0.980 (95% CI: 0.942- 1, p<0.001) at an optimal cut-off point of 1.76, 100% sensitivity and 98% specificity. Conclusion: Our findings have, for the first time, demonstrated that circulating LINC01538 are highly expressed in patients with MI, functioning as potential novel biomarker for diagnosis.