scholarly journals Exosomal Long NonCoding Rnas as Cancer Biomarkers and Therapeutic Targets

2020 ◽  
Vol 9 (4) ◽  
pp. 297-304
Author(s):  
O. A. Beylerli ◽  
I. F. Gareev ◽  
V. N. Pavlov ◽  
Zhao Shiguang ◽  
Chen Xin ◽  
...  

Extensive study of extracellular vesicles began about ten years ago. Exosomes are extracellular membrane vesicles 30–100 nm in diameter secreted by various types of cells and present in most biological fluids. For a long time they were considered non-functional cellular components. However, it has been proven that they serve as a means of intercellular exchange of information. They can move bioactive molecules such as proteins, lipids, RNA, and DNA. Several studies have shown that their contents, including proteins and non-coding nucleic acids, may be of particular interest as biomarkers of diseases. The most promising of all these molecules are non-coding RNAs (ncRNAs), including microRNAs and long non-coding RNAs (lncRNAs). LncRNAs are a large group of non-coding RNAs (ncRNAs) longer than 200 nucleotides. As regulatory factors lncRNAs play an important role in complex cellular processes, such as apoptosis, growth, differentiation, proliferation, etc. Despite many advances in diagnosis and treatment (surgery, radiation therapy, chemotherapy), cancer remains one of the most important public healthcare problems worldwide. Every day brings a better understanding of the role of exosomes in the development of cancer and metastases. Liquid biopsy has been developed as a method for the detection of cancer at an early stage. This is a series of minimally invasive tests of bodily fluids offering the advantage of real-time tracking of the tumour development. In fact, circulating exosomal lncRNAs have been found to be closely linked to processes of oncogenesis, metastasis and treatment. In this paper we review current studies into the functional role of exosomal lncRNAs in cancer and discuss their potential clinical use as diagnostic biomarkers and therapeutic targets for cancer.

2021 ◽  
Vol 19 ◽  
Author(s):  
Xiang Wang ◽  
Changmei HuangFu ◽  
Xiudeng Zhu ◽  
Jiehong Liu ◽  
Xinqin Gong ◽  
...  

Abstract: Aging has been considered to be the most important non-modifiable risk factor for stroke and death. Changes in circulation factors in the systemic environment, cellular senescence and artery hypertension during human ageing have been investigated. Exosomes are nanosize membrane vesicles that can regulate target cell functions via delivering their carried bioactive molecules (e.g. protein, mRNA, and microRNAs). In the central nervous system, exosomes and exosomal microRNAs play a critical role in regulating neurovascular function, and are implicated in the initiation and progression of stroke. MicroRNAs are small non-coding RNAs that have been reported to play critical roles in various biological processes. Recently, evidence has shown that microRNAs are packaged into exosomes and can be secreted into the systemic and tissue environment. Circulating microRNAs participate in cellular senescence and contribute to age-associated stroke. Here, we provide an overview of current knowledge on exosomes and their carried microRNAs in the regulation of cellular and organismal ageing processes, demonstrating the potential role of exosomes and their carried microRNAs in age-associated stroke.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2878
Author(s):  
Claudia Maria Hattinger ◽  
Maria Pia Patrizio ◽  
Leonardo Fantoni ◽  
Chiara Casotti ◽  
Chiara Riganti ◽  
...  

High-grade osteosarcoma (HGOS), the most common primary malignant tumor of bone, is a highly aggressive neoplasm with a cure rate of approximately 40–50% in unselected patient populations. The major clinical problems opposing the cure of HGOS are the presence of inherent or acquired drug resistance and the development of metastasis. Since the drugs used in first-line chemotherapy protocols for HGOS and clinical outcome have not significantly evolved in the past three decades, there is an urgent need for new therapeutic biomarkers and targeted treatment strategies, which may increase the currently available spectrum of cure modalities. Unresponsive or chemoresistant (refractory) HGOS patients usually encounter a dismal prognosis, mostly because therapeutic options and drugs effective for rescue treatments are scarce. Tailored treatments for different subgroups of HGOS patients stratified according to drug resistance-related biomarkers thus appear as an option that may improve this situation. This review explores drug resistance-related biomarkers, therapeutic targets and new candidate treatment strategies, which have emerged in HGOS. In addition to consolidated biomarkers, specific attention has been paid to the role of non-coding RNAs, tumor-derived extracellular vesicles, and cancer stem cells as contributors to drug resistance in HGOS, in order to highlight new candidate markers and therapeutic targets. The possible use of new non-conventional drugs to overcome the main mechanisms of drug resistance in HGOS are finally discussed.


Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1003-1011
Author(s):  
Guanyu Zhang ◽  
Yiran Li ◽  
Jiasheng Xu ◽  
Zhenfang Xiong

AbstractOsteosarcoma (OS) is the most common primary malignant tumor of the skeletal system in the clinic. It mainly occurs in adolescent patients and the pathogenesis of the disease is very complicated. The distant metastasis may occur in the early stage, and the prognosis is poor. MicroRNAs (miRNAs) are non-coding RNAs of about 18–25 nt in length that are involved in post-transcriptional regulation of genes. miRNAs can regulate target gene expression by promoting the degradation of target mRNAs or inhibiting the translation process, thereby the proliferation of OS cells can be inhibited and the apoptosis can be promoted; in this way, miRNAs can affect the metabolism of OS cells and can also participate in the occurrence, invasion, metastasis, and recurrence of OS. Some miRNAs have already been found to be closely related to the prognosis of patients with OS. Unlike other reviews, this review summarizes the miRNA molecules closely related to the development, diagnosis, prognosis, and treatment of OS in recent years. The expression and influence of miRNA molecule on OS were discussed in detail, and the related research progress was summarized to provide a new research direction for early diagnosis and treatment of OS.


2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Mariam Murtadha ◽  
Muller Fabbri

AbstractMicroRNAs (miRs) are small non-coding RNAs with key gene regulatory functions. Recent evidence has shown that miRs have a central role in shaping the biology of the Tumor Microenvironment (TME). The discovery that some exosomes contain high levels of miR cargo that shuttle between cells and mediate intercellular cross-talk has shifted the focus of miR research towards understanding the biological role of exosomic miRs. In this review, we highlight the emerging role of exosomic miRs in molding the tumor microenvironment towards pro-tumor conditions by altering intercellular communication. We briefly discuss some mechanisms of selective loading of miRs into exosomes, as well as emerging evidence that exosomic miRs are present in all biological fluids. Furthermore, we describe the differences in the exosomic miR signatures between cancer patients and healthy controls, and the potential role of exosomic miRs as diagnostic, prognostic, and therapeutic biomarkers.


Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5919
Author(s):  
Cristina Barbagallo ◽  
Chiara Bianca Maria Platania ◽  
Filippo Drago ◽  
Davide Barbagallo ◽  
Cinzia Di Pietro ◽  
...  

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, showing a high mortality due to metastasis. Although it is considered a rare disease, a growing number of papers have reported altered levels of RNAs (i.e., coding and non-coding RNAs) in cancerous tissues and biological fluids from UM patients. The presence of circulating RNAs, whose dysregulation is associated with UM, paved the way to the possibility of exploiting it for diagnostic and prognostic purposes. However, the biological meaning and the origin of such RNAs in blood and ocular fluids of UM patients remain unexplored. In this review, we report the state of the art of circulating RNAs in UM and debate whether the amount and types of RNAs measured in bodily fluids mirror the RNA alterations from source cancer cells. Based on literature data, extracellular RNAs in UM patients do not represent, with rare exceptions, a snapshot of RNA dysregulations occurring in cancerous tissues, but rather the complex and heterogeneous outcome of a systemic dysfunction, including immune system activity, that modifies the mechanisms of RNA delivery from several cell types.


2021 ◽  
Vol 20 ◽  
pp. 153303382110378
Author(s):  
Qian Zhang ◽  
Xiangling Yang ◽  
Huanliang Liu

Metabolic reprogramming is one of the most common characteristics of cancer cells. The metabolic alterations of glucose, amino acids and lipids can support the aggressive phenotype of cancer cells. Exosomes, a kind of extracellular vesicles, participate in the intercellular communication through transferring bioactive molecules. Increasing evidence has demonstrated that enzymes, metabolites and non-coding RNAs in exosomes are responsible for the metabolic alteration of cancer cells. In this review, we summarize the past and recent findings of exosomes in altering cancer metabolism and elaborate on the role of the specific enzymes, metabolites and non-coding RNAs transferred by exosomes. Moreover, we give evidence of the role of exosomes in cancer diagnosis and treatment. Finally, we discuss the existing problems in the study and application of exosomes in cancer diagnosis and treatment.


2017 ◽  
Vol 20 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Elena Sergeevna Kamyshova ◽  
Irina Nikolaevna Bobkova ◽  
Irina Mikhailovna Kutyrina

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus associated with the progressive deterioration of renal function. Although microalbuminuria is considered as a gold standard for DN diagnosis, it has limited predictive powers and specificity as a diagnostic tool for the early stage of DN. Therefore, new biomarkers are required for the early detection of DN. Studies using in vitro and in vivo models of DN have revealed an important role of microRNAs (miRNAs), short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression, in DN development. Recent studies have shown that the dysregulation of miRNAs, which is associated with the key features of DN, such as the mesangial expansion and accumulation of extracellular matrix proteins, is related to fibrosis and glomerular dysfunction. Thus, the up- and downregulation of miRNA expression in the renal tissue or biological fluids, including urine, may represent new biomarkers for the diagnosis and monitoring of DN progression. In this review, we highlight the significance of miRNAs as biomarkers for the early detection of DN and emphasise their potential role as a therapeutic target.


2021 ◽  
Vol 15 ◽  
Author(s):  
Yuanyuan Liang ◽  
Lin Wang

Alzheimer’s disease (AD) is the most common cause of senile dementia. Although AD research has made important breakthroughs, the pathogenesis of this disease remains unclear, and specific AD diagnostic biomarkers and therapeutic strategies are still lacking. Recent studies have demonstrated that neuroinflammation is involved in AD pathogenesis and is closely related to other health effects. MicroRNAs (miRNAs) are a class of endogenous short sequence non-coding RNAs that indirectly inhibit translation or directly degrade messenger RNA (mRNA) by specifically binding to its 3′ untranslated region (UTR). Several broadly expressed miRNAs including miR-21, miR-146a, and miR-155, have now been shown to regulate microglia/astrocytes activation. Other miRNAs, including miR-126 and miR-132, show a progressive link to the neuroinflammatory signaling. Therefore, further studies on these inflamma-miRNAs may shed light on the pathological mechanisms of AD. The differential expression of inflamma-miRNAs (such as miR-29a, miR-125b, and miR-126-5p) in the peripheral circulation may respond to AD progression, similar to inflammation, and therefore may become potential diagnostic biomarkers for AD. Moreover, inflamma-miRNAs could also be promising therapeutic targets for AD treatment. This review provides insights into the role of inflamma-miRNAs in AD, as well as an overview of general inflamma-miRNA biology, their implications in pathophysiology, and their potential roles as biomarkers and therapeutic targets.


2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Iqra Khalid ◽  
Azra Quraishi ◽  
Freeha Fiaz

Poor and late diagnosis of HCV is main the cause of liver cancer. MicroRNAs are non-coding molecules that are involved in regulation of a variety of functions happening in the cell, in healthy and diseased state. Dysregulation of microRNAs is observed in different diseases, especially in liver cancer like hepatocellular carcinoma. The available detection methods detect HCC at a late stage. There is a need to find novel biomarkers for diagnosis at an earlier stage to minimize chances of liver cancer. Circulating microRNAs are novel and minimal invasive markers for early detection of HCV based hepatocellular carcinoma. In this review, the current progress on the potential role of miRNA as biomarkers for detection of HCC and therapeutic targets are summarized. We concluded that the expression of microRNAis upregulated in the patients of hepatocellular carcinoma when compared with the healthy ones. In-depth studies of miRNA in patients of HCC as genetic biomarkers will improve the diagnosis. It will also improve the prognosis of early stage HCC patients. This will also help in identifying a suitable and effective therapeutic targets so as to reduce the chances of failure of chemotherapy.


2020 ◽  
Vol 25 (42) ◽  
pp. 4523-4535 ◽  
Author(s):  
Chao Tu ◽  
Jieyu He ◽  
Ruiqi Chen ◽  
Zhihong Li

: Exosomes are phospholipid bilayer-enclosed membrane vesicles derived and constitutively secreted by various metabolically active cells. They are capable of mediating hetero- and homotypic intercellular communication by transferring multiple cargos from donor cells to recipient cells. Nowadays, non-coding RNAs (ncRNAs) have emerged as novel potential biomarkers or disease-targeting agents in a variety of diseases. However, the lack of effective delivery systems may impair their clinical application. Recently, accumulating evidence demonstrated that ncRNAs could be efficiently delivered to recipient cells using exosomes as a carrier, and therefore can exert a critical role in musculoskeletal diseases including osteoarthritis, rheumatoid arthritis, osteoporosis, muscular dystrophies, osteosarcoma and other diseases. Herein, we present an extensive review of biogenesis, physiological relevance and clinical implication of exosome-derived ncRNAs in musculoskeletal diseases.


Sign in / Sign up

Export Citation Format

Share Document