scholarly journals Long Noncoding RNAs in Pathological Cardiac Remodeling: A Review of the Update Literature

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Huan Zhou ◽  
Bin Wang ◽  
Ying-xi Yang ◽  
Qiu-jin Jia ◽  
Ao Zhang ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Vascular Remodeling ◽  
Target Gene ◽  
Myocardial Hypertrophy ◽  
Cardiac Fibroblasts ◽  
Noncoding Rnas ◽  
Therapeutic Targets ◽  
Underlying Mechanism ◽  
Long Noncoding Rnas ◽  
Myocardial Remodeling

Cardiac remodeling is a self-regulatory response of the myocardium and vasculature under the stressful condition. Cardiomyocytes (CMs), vascular smooth muscle cells (VSMCs), endothelial cells (ECs), and cardiac fibroblasts (CFs) are all involved in this process, characterized by change of morphological structures and mechanical/chemical activities as well as metabolic patterns. Despite current development of consciousness, the control of cardiac remodeling remains unsatisfactory, and to further explore the underlying mechanism and seek the optimal therapeutic targets is still the urgent need in clinical practice. It is now emerging that long noncoding RNAs (lncRNAs) play key regulatory roles in these adverse responses: lncRNA TUG1, AK098656, TRPV1, GAS5, Giver, and Lnc-Ang362 have been indicated in hypertension-related vascular remodeling, H19, TUG1, UCA1, MEG3, APPAT, and lincRNA-p21 in atherosclerosis (AS), and HIF1A-AS1 and Lnc-HLTF-5 in aortic aneurysm (AA). In addition, Neat1, AK139328, APF, CAIF, AK088388, CARL, MALAT1, HOTAIR, XIST, and NRF are involved in postischemia myocardial remodeling, while Mhrt, Chast, CHRF, ROR, H19, Plscr4, and MIAT are involved in myocardial hypertrophy, and MALAT1, wisper, MEG3, and H19 are involved in extracellular matrix (ECM) reconstitution. Signaling to specific miRNAs by acting as endogenous sponge (ceRNA) was the main form that regulates the target gene expression during cardiac remodeling. This review will underline the updates of lncRNAs and lncRNA-miRNA interactions in maladaptive remodeling and also cast light on their potential roles as therapeutic targets, hoping to provide supportive background for following research.

scholarly journals Long Noncoding RNAs Involved in the Endocrine Therapy Resistance of Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1424 ◽  
Author(s):  
Toshihiko Takeiwa ◽  
Kazuhiro Ikeda ◽  
Yuichi Mitobe ◽  
Kuniko Horie-Inoue ◽  
Satoshi Inoue
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Noncoding Rnas ◽  
Therapeutic Targets ◽  
Therapy Resistance ◽  
Long Noncoding Rnas ◽  
Endocrine Therapy Resistance ◽  
New Biomarkers

Long noncoding RNAs (lncRNAs) are defined as RNAs longer than 200 nucleotides that do not encode proteins. Recent studies have demonstrated that numerous lncRNAs are expressed in humans and play key roles in the development of various types of cancers. Intriguingly, some lncRNAs have been demonstrated to be involved in endocrine therapy resistance for breast cancer through their own mechanisms, suggesting that lncRNAs could be promising new biomarkers and therapeutic targets of breast cancer. Here, we summarize the functions and mechanisms of lncRNAs related to the endocrine therapy resistance of breast cancer.

Long noncoding RNAs in cancer: From discovery to therapeutic targets

2020 ◽  
pp. 105-147 ◽  
Author(s):  
Ramesh Choudhari ◽  
Melina J. Sedano ◽  
Alana L. Harrison ◽  
Ramadevi Subramani ◽  
Ken Y. Lin ◽  
...  
Keyword(s):  
Noncoding Rnas ◽  
Therapeutic Targets ◽  
Long Noncoding Rnas

264The long noncoding RNA H19 modulates cardiac remodeling after infarction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O K Choong ◽  
C Y Chen ◽  
J H Lin ◽  
P J Lin ◽  
J H Zhang ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Noncoding Rna ◽  
Cardiac Fibrosis ◽  
Cardiac Development ◽  
Cardiac Fibroblasts ◽  
Noncoding Rnas ◽  
Interacting Protein ◽  
Functional Studies ◽  
Rna Purification

Abstract Noncoding RNAs account for 80% of human transcripts, but functional studies on noncoding RNAs are relatively few and limited. Long noncoding RNAs (lncRNAs) are known to have an important role in cardiac development, and lately, high-throughput RNA sequencing has been extensively utilized to profile and explore the transcriptome landscape of lncRNAs in failing hearts. These studies have revealed that lncRNAs are mostly dysregulated in failing hearts and their expression signature can discriminate failing hearts of different etiologies. H19 is abundantly expressed in failing human hearts and its polymorphism was shown to possess a significant correlation with the risk of coronary artery diseases. In our study using murine hearts, we discovered that H19 was significantly up regulated in the heart after ischemic injury, with predominant expression in cardiac fibroblasts. This finding piqued our interest to further investigate the function of H19 in the heart. We demonstrated that ectopic overexpression of H19 using the AAV approach led to severe cardiac fibrosis in mouse hearts following myocardial infarction. In light of this finding, we generated H19 knockout mice to further investigate the functionality of H19 and we found that cardiac fibrosis was attenuated in these mice. Altogether, these findings suggested that H19 is a fibrosis regulator during cardiac remodeling process after infarction. Due to the multiple regulatory roles of lncRNAs, we then took advantage of chromatin isolation by RNA purification (ChIRP) to identify the H19-interacting protein, YB-1. Surprisingly, mice with YB-1 knockdown displayed severe cardiac fibrosis even without injury. Furthermore, we demonstrated that YB-1 is a transcriptional suppressor of collagen 1A1. Knockout of H19 in YB-1 knockdown partially suppressed Col1a1 expression, which suggests a negative regulatory role of H19 on YB-1 towards the expression of Col1a1. Taking into account all of these findings, we concluded that H19 mediates collagen expression in fibroblasts through the inhibition of YB-1 activity during cardiac remodeling.

scholarly journals Long Noncoding RNA Rps4l Mediates the Proliferation of Hypoxic Pulmonary Artery Smooth Muscle Cells

Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1124-1133 ◽  
Author(s):  
Ying Liu ◽  
Hongyue Zhang ◽  
Yiying Li ◽  
Lixin Yan ◽  
Wei Du ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Vascular Remodeling ◽  
Cell Cycle Progression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Cycle Progression ◽  
Pulmonary Artery Smooth Muscle

Pulmonary hypertension (PH) is a rare and fatal disorder involving the vascular remodeling of pulmonary arteries mediated by the enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs). Long noncoding RNAs are a subclass of regulatory molecules with diverse cellular functions, but their role in PH remains largely unexplored. We aimed to identify and determine the functions of long noncoding RNAs involved in hypoxia-induced PH and PASMC proliferation. RNA sequencing in a hypoxic mouse model identified hypoxia-regulated long noncoding RNAs, including Rps4l. Rps4l expression was significantly reduced in PH-model mice and hypoxic PASMCs. The subcellular localization of Rps4l was detected by RNA fluorescence in situ hybridization and quantification of nuclear/cytoplasmic RNA. Rps4l overexpression rescued pulmonary arterial hypertension features, as demonstrated by right ventricle hypertrophy, right ventricular systolic pressure, hemodynamics, cardiac function, and vascular remodeling. At the cellular level, Rps4l overexpression weakened cell viability and proliferation and suppressed cell cycle progression. Potential Rps4l-binding proteins were identified via RNA pull-down followed by mass spectrometry, RNA immunoprecipitation, and microscale thermophoresis. These results indicated that Rps4l is associated with and affects the stabilization of ILF3 (interleukin enhancer-binding factor 3). Rps41 further regulates the levels of HIF-1α and consequently leads to hypoxia-induced PASMC proliferation and migration. Our results showed that in hypoxic PASMCs, Rps4l expression decreases due to regulation by hypoxia. This decrease affects the proliferation, migration, and cell cycle progression of PASMCs through ILF3/HIF-1α. These results provide a theoretical basis for further investigations into the pathological mechanism of hypoxic PH and may provide insight for the development of novel treatments.

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