The role of non-coding RNA/microRNAs in cardiac disease

In the past two decades, our knowledge about non-coding DNA has increased tremendously. While non-coding DNA was initially discarded as ‘junk DNA’, we are now aware of the important and often crucial roles of RNA transcripts that do not translate into protein. Non-coding RNAs (ncRNAs) play important functions in normal cellular homeostasis and also in many diseases across all organ systems. Among the different ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been studied the most. In this chapter we discuss the role of miRNAs and lncRNAs in cardiac disease. We present examples of miRNAs with fundamental roles in cardiac development (miR-1), hypertrophy (myomiRs, miR-199, miR-1/133), fibrosis (miR-29, miR-21), myocardial infarction (miR-15, miR17~92), and arrhythmias/conduction (miR-1). We provide examples of lncRNAs related to cardiac hypertrophy (MHRT, CHRF), myocardial infarction (ANRIL, MIAT), and arrhythmias (KCNQ1OT1). We also discuss miRNAs and lncRNAs as potential therapeutic targets or biomarkers in cardiac disease.

Evolutionary Patterns of Non-Coding RNA in Cardiovascular Biology

Non-Coding RNA ◽

10.3390/ncrna5010015 ◽

2019 ◽

Vol 5 (1) ◽

pp. 15 ◽

Cited By ~ 5

Author(s):

Shrey Gandhi ◽

Frank Ruehle ◽

Monika Stoll

Keyword(s):

Vascular System ◽

Functional Characterization ◽

Evolutionary Patterns ◽

Protein Coding ◽

Rna Transcripts ◽

Non Coding Rna ◽

High Prevalence ◽

Cardiovascular Biology ◽

Cardiovascular diseases (CVDs) affect the heart and the vascular system with a high prevalence and place a huge burden on society as well as the healthcare system. These complex diseases are often the result of multiple genetic and environmental risk factors and pose a great challenge to understanding their etiology and consequences. With the advent of next generation sequencing, many non-coding RNA transcripts, especially long non-coding RNAs (lncRNAs), have been linked to the pathogenesis of CVD. Despite increasing evidence, the proper functional characterization of most of these molecules is still lacking. The exploration of conservation of sequences across related species has been used to functionally annotate protein coding genes. In contrast, the rapid evolutionary turnover and weak sequence conservation of lncRNAs make it difficult to characterize functional homologs for these sequences. Recent studies have tried to explore other dimensions of interspecies conservation to elucidate the functional role of these novel transcripts. In this review, we summarize various methodologies adopted to explore the evolutionary conservation of cardiovascular non-coding RNAs at sequence, secondary structure, syntenic, and expression level.

Long Non-Coding RNA in the Pathogenesis of Cancers

Cells ◽

10.3390/cells8091015 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1015 ◽

Cited By ~ 72

Author(s):

Chi ◽

Wang ◽

Yu ◽

Yang

Keyword(s):

Early Stage ◽

Gene Expressions ◽

Rna Transcripts ◽

The Past ◽

Non Coding Rna ◽

Incidence And Mortality ◽

Non Coding Rnas ◽

Tumor Growth And Metastasis ◽

New Biomarkers ◽

The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of the cancers cannot be effectively diagnosed at the early stage. Although there are multiple therapeutic treatments, including surgery, radiotherapy, chemotherapy, and targeted drugs, their effectiveness is still limited. The overall survival rate of malignant cancers is still low. It is necessary to further study the mechanisms for malignant cancers, and explore new biomarkers and targets that are more sensitive and effective for early diagnosis, treatment, and prognosis of cancers than traditional biomarkers and methods. Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with a length greater than 200 nucleotides. Generally, lncRNAs are not capable of encoding proteins or peptides. LncRNAs exert diverse biological functions by regulating gene expressions and functions at transcriptional, translational, and post-translational levels. In the past decade, it has been demonstrated that the dysregulated lncRNA profile is widely involved in the pathogenesis of many diseases, including cancer, metabolic disorders, and cardiovascular diseases. In particular, lncRNAs have been revealed to play an important role in tumor growth and metastasis. Many lncRNAs have been shown to be potential biomarkers and targets for the diagnosis and treatment of cancers. This review aims to briefly discuss the latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis of certain malignant cancers, including lung, breast, liver, and colorectal cancers, as well as hematological malignancies and neuroblastoma.

CIRCULAR RNA – miRNA MEDIATED INTERACTION IN MYOCARDIAL INFARCTION

Journal of IMAB - Annual Proceeding (Scientific Papers) ◽

10.5272/jimab.2021272.3793 ◽

2021 ◽

Vol 27 (2) ◽

pp. 3793-3798

Author(s):

Yordanka Doneva ◽

◽

Veselin Valkov ◽

Yavor Kashlov ◽

Galya Mihaylova ◽

...

Keyword(s):

Gene Expression ◽

Myocardial Infarction ◽

Circular Rna ◽

Biological Functions ◽

Non Coding Rna ◽

Circular Structure ◽

Wide Range ◽

Non Coding Rnas ◽

Circular RNA (circRNAs) belong to the long non-coding RNA family, but unlike the linear RNA in circular RNA, the 3’ and 5’ end in the RNA molecule are joined together, forming their circular structure. Until recently, circRNAs have been believed to be a side product of splicing, but now it is known that they have a wide range of biological functions, from regulators of gene expression to regulators of other non-coding RNAs - microRNAs (miRNAs). CircRNAs have the potential of being therapeutic targets and biomarkers for diseases. There are little data and only several investigations about this type of RNAs in myocardial infarction in humans. This review summarizes the role of some new circRNA – miRNA interactions in the development of Myocardial Infarction.

Genome-wide analysis of long non-coding RNA expression and function in colorectal cancer

Tumor Biology ◽

10.1177/1010428317703650 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831770365 ◽

Cited By ~ 10

Author(s):

Fangyuan Jing ◽

Huicheng Jin ◽

Yingying Mao ◽

Yingjun Li ◽

Ye Ding ◽

...

Keyword(s):

Colorectal Cancer ◽

Expression Profile ◽

Colorectal Carcinogenesis ◽

Rna Expression ◽

Rna Transcripts ◽

Non Coding Rna ◽

Tumor Tissues ◽

Non Coding Rnas ◽

Long non-coding RNAs (lncRNAs) are widely transcribed in the genome, but their expression profile and roles in colorectal cancer are not well understood. The aim of this study was to investigate the long non-coding RNA expression profile in colorectal cancer and look for potential diagnostic biomarkers of colorectal cancer. Long non-coding RNA microarray was applied to investigate the global long non-coding RNA expression profile in colorectal cancer. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using standard enrichment computational methods. The expression levels of selected long non-coding RNAs were validated by quantitative reverse transcription polymerase chain reaction. The relationship between long non-coding RNA expression levels and clinicopathological characteristics of colorectal cancer patients was assessed. Coexpression analyses were carried out to find the coexpressed genes of differentially expressed long non-coding RNAs, followed by gene ontology analysis to predict the possible role of the selected long non-coding RNAs in colorectal carcinogenesis. In this study, a total of 1596 long non-coding RNA transcripts and 1866 messenger RNA transcripts were dysregulated in tumor tissues compared with paired normal tissues. The top upregulated long non-coding RNAs in tumor tissues were CCAT1, UCA1, RP5-881L22.5, NOS2P3, and BC005081 and the top downregulated long non-coding RNAs were AK055386, AC078941.1, RP4-800J21.3, RP11-628E19.3, and RP11-384P7.7. Long non-coding RNA UCA1 was significantly upregulated in colon cancer, and AK055386 was significantly downregulated in tumor with dimension <5 cm. Functional prediction analyses showed that both the long non-coding RNAs coexpress with cell cycle related messenger RNAs. The current long non-coding RNA study provided novel insights into expression profile in colorectal cancer and predicted the potential roles of long non-coding RNAs in colorectal carcinogenesis. Among the dysregulated long non-coding RNAs, UCA1 was found to be associated with anatomic site, and AK055386 was found associated with tumor size. Further functional investigations into the molecular mechanisms are warranted to clarify the role of long non-coding RNA in colorectal carcinogenesis.

On Future Directions in Pathology

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053991 ◽

1982 ◽

Vol 40 ◽

pp. 274-277

Author(s):

Benjamin F. Trump ◽

Irene K. Berezesky ◽

Raymond T. Jones

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Clinical Pathology ◽

Future Directions ◽

Diagnostic Pathology ◽

The Past ◽

Transmission Electron ◽

Organ Systems ◽

The Many

The role of electron microscopy and associated techniques is assured in diagnostic pathology. At the present time, most of the progress has been made on tissues examined by transmission electron microscopy (TEM) and correlated with light microscopy (LM) and by cytochemistry using both plastic and paraffin-embedded materials. As mentioned elsewhere in this symposium, this has revolutionized many fields of pathology including diagnostic, anatomic and clinical pathology. It began with the kidney; however, it has now been extended to most other organ systems and to tumor diagnosis in general. The results of the past few years tend to indicate the future directions and needs of this expanding field. Now, in addition to routine EM, pathologists have access to the many newly developed methods and instruments mentioned below which should aid considerably not only in diagnostic pathology but in investigative pathology as well.

Emerging role of a novel small non-coding regulatory RNA: tRNA-derived small RNA

ExRNA ◽

10.1186/s41544-019-0036-7 ◽

2019 ◽

Vol 1 (1) ◽

Author(s):

Fangfang Jin ◽

Zhigang Guo

Keyword(s):

Small Rna ◽

Current Knowledge ◽

Future Research ◽

Regulatory Rna ◽

Biological Functions ◽

Research Directions ◽

Non Coding Rna ◽

Future Research Directions ◽

Abstract The discovery of small non-coding RNAs, such as miRNA and piRNA, has dramatically changed our understanding of the role RNA plays in organisms. Recent studies show that a novel small non-coding RNA generated from cleavage of tRNA or pre-tRNA, called tRNA-derived small RNA (tsRNA), serves as a new regulator of gene expression. tsRNA has been determined participate in regulating some specific physiological and pathological processes. Although knowledge regarding the biological roles of miRNA and piRNA is expanding, whether tsRNAs play similar roles remains poorly understood. Here, we review the current knowledge regarding the mechanisms of action and biological functions of tsRNAs in intracellular, extracellular and intergenerational inheritance, and highlight the potential application of tsRNAs in human diseases, and present the current problems and future research directions.

Long Non-coding RNA XIST Attenuates Diabetic Peripheral Neuropathy by Inducing Autophagy Through MicroRNA-30d-5p/sirtuin1 Axis

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.655157 ◽

2021 ◽

Vol 8 ◽

Author(s):

Bei-Yan Liu ◽

Lin Li ◽

Li-Wei Bai ◽

Chang-Shui Xu

Keyword(s):

Oxidative Stress ◽

Peripheral Neuropathy ◽

Schwann Cells ◽

Diabetic Peripheral Neuropathy ◽

Beclin 1 ◽

Diabetic Mice ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus (Feldman et al., 2017) complication and the primary reason for amputation. Meanwhile, long non-coding RNAs (lncRNAs) are a type of regulatory non-coding RNAs (ncRNAs) that broadly participate in DPN development. However, the correlation of lncRNA X-inactive specific transcript (XIST) with DPN remains unclear. In this study, we were interested in the role of XIST in the modulation of DPN progression. Significantly, our data showed that the expression of XIST and sirtuin1 (SIRT1) was inhibited, and the expression of microRNA-30d-5p (miR-30d-5p) was enhanced in the trigeminal sensory neurons of the diabetic mice compared with the normal mice. The levels of LC3II and Beclin-1 were inhibited in the diabetic mice. The treatment of high glucose (HG) reduced the XIST expression in Schwann cells. The apoptosis of Schwann cells was enhanced in the HG-treated cells, but the overexpression of XIST could block the effect in the cells. Moreover, the levels of LC3II and Beclin-1 were reduced in the HG-treated Schwann cells, while the overexpression of XIST was able to reverse this effect. The HG treatment promoted the production of oxidative stress, while the XIST overexpression could attenuate this result in the Schwann cells. Mechanically, XIST was able to sponge miR-30d-5p and miR-30d-5p-targeted SIRT1 in the Schwann cells. MiR-30d-5p inhibited autophagy and promoted oxidative stress in the HG-treated Schwann cells, and SIRT1 presented a reversed effect. MiR-30d-5p mimic or SIRT1 depletion could reverse XIST overexpression-mediated apoptosis and autophagy of the Schwann cells. Thus, we concluded that XIST attenuated DPN by inducing autophagy through miR-30d-5p/SIRT1 axis. XIST and miR-30d-5p may be applied as the potential targets for DPN therapy.

Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

Bioscience Reports ◽

10.1042/bsr20191764 ◽

2020 ◽

Vol 40 (4) ◽

Cited By ~ 1

Author(s):

Chong Lu ◽

Xiuhua Wang ◽

Xiangwang Zhao ◽

Yue Xin ◽

Chunping Liu

Keyword(s):

Breast Cancer ◽

Normal Breast ◽

Tumor Promoter ◽

Women Health ◽

Non Coding Rna ◽

Non Coding Rnas ◽

And Migration ◽

Breast Tissues ◽

Abstract Breast cancer (BC) poses a great threaten to women health. Numerous evidences suggest the important role of long non-coding RNAs (lncRNAs) in BC development. In the present study, we intended to investigate the role of ARAP1-AS1 in BC progression. First of all, the GEPIA data suggested that ARAP1-AS1 was highly expressed in breast invasive carcinoma (BRAC) tissues compared with the normal breast tissues. Meanwhile, the expression of ARAP1-AS1 was greatly up-regulated in BC cell lines. ARAP1-AS1 knockdown led to repressed proliferation, strengthened apoptosis and blocked migration of BC cells. Moreover, ARAP1-AS1 could boost HDAC2 expression in BC through sponging miR-2110 via a ceRNA mechanism. Of note, the UCSC predicted that HDAC2 was a potential transcriptional regulator of PLIN1, an identified tumor suppressor in BC progression. Moreover, we explained that the repression of HDAC2 on PLIN1 was owing to its deacetylation on PLIN1 promoter. More importantly, depletion of PLIN1 attenuated the mitigation function of ARAP1-AS1 silence on the malignant phenotypes of BC cells. To sum up, ARAP1-AS1 serves a tumor-promoter in BC development through modulating miR-2110/HDAC2/PLIN1 axis, which may help to develop novel effective targets for BC treatment.

The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation

International Journal of Molecular Sciences ◽

10.3390/ijms22179165 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9165

Author(s):

David Roig-Carles ◽

Holly Jackson ◽

Katie F. Loveson ◽

Alan Mackay ◽

Rebecca L. Mather ◽

...

Keyword(s):

Large Family ◽

Diffuse Intrinsic Pontine Glioma ◽

Locked Nucleic Acid ◽

Normal Brain ◽

Pontine Glioma ◽

Incurable Cancer ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated H19 lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of H19 lncRNA in paediatric high-grade gliomas (pedHGGs). The expression and sub-cellular location of H19 lncRNA were validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of H19 in DIPG cells. We found that H19 expression was higher in DIPG vs. normal brain tissue and other pedHGGs. H19 knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, H19 buffers let-7 microRNAs, resulting in the up-regulation of oncogenic let-7 target (e.g., SULF2 and OSMR). H19 is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate for treating this incurable cancer.

Regulatory Role of N6-methyladenosine (m6A) Modification in Osteosarcoma

Frontiers in Oncology ◽

10.3389/fonc.2021.683768 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yujie Zhang ◽

Yanyan Wang ◽

Liwei Ying ◽

Sifeng Tao ◽

Mingmin Shi ◽

...

Keyword(s):

Molecular Mechanism ◽

Research Trends ◽

Rna Modification ◽

Future Research ◽

Related Factors ◽

The Past ◽

Pathophysiological Role ◽

Primary Bone ◽

Osteosarcoma is the most common primary bone malignancy, typically occurring in childhood or adolescence. Unfortunately, the clinical outcomes of patients with osteosarcoma are usually poor because of the aggressive nature of this disease and few treatment advances in the past four decades. N6-methyladenosine (m6A) is one of the most extensive forms of RNA modification in eukaryotes found both in coding and non-coding RNAs. Accumulating evidence suggests that m6A-related factors are dysregulated in multiple osteosarcoma processes. In this review, we highlight m6A modification implicated in osteosarcoma, describing its pathophysiological role and molecular mechanism, as well as future research trends and potential clinical application in osteosarcoma.