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Annual Review | 2017 Exomes Heavyweight Study at a glance, this is enough

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The past 2017 is also a year in which the heat of exosome research continues to heat up, and significant research progress has been made in many fields. Today, let's review the 2017 "Exogenous Year"!


1. Nature: Efficacy of exosomes as RNAi drug carriers

Corresponding author: Raghu Kalluri

Author unit: US MD Anderson Cancer Center

PMID: 28607485


Highlights:

This study examined the effects of using exosomes as RNAi-targeted drugs and demonstrated the mechanism by which exosomes perform immune escape during this process: genetic modification of exosomes (designated iExosome), loading of KRAS mutant genes targeting pancreatic cancer cells The RNA interference drug, tested on a mouse model, showed that iExosome delivered better than the same modified lipid iLiposome and inhibited the growth of invasive pancreatic cancer; this benefited from the CD47 on the surface of exosomes, which prevented Exosomes are cleared by monocytes in the blood circulatory system. The results of this study are exciting for scientists working on exosomes translational medicine!


2. Nature: regulation of adipose tissue exosomes miRNA

Corresponding author: C Ronald Kahn.

Author: Harvard Medical School Joslin Diabetes Center

PMID: 28199304


Highlights:

In February 2017, this research article, which cannot be ignored, published that the exosomes secreted by adipose tissue regulate liver function through the miRNAs they carry, which have a potentially important role in metabolic changes and disease occurrence.


3. Cell: exosome miRNA regulates insulin sensitivity

Corresponding author: Jerrold M. Olefsky

Author unit: University of California, San Diego

PMID: 28942920


Highlights:

Chronic tissue inflammation caused by obesity is the underlying cause of insulin resistance and type 2 diabetes. In September, the study published in Cell found that exosome-mediated intercellular communication led to metabolic disorders in diabetes, and that miRNAs carried by exosomes were involved in the key mechanisms of diabetes. The experiments carried out in the article are classical and convincing exosome studies. For example, only three experiments were performed using electron microscopy, NTA and Western blot markers to demonstrate successful exosome extraction. The author also mentioned in the experimental method section that he followed the experimental advice of the exosomal knowledge base EV-TRACK established by exosome scientists such as Théry C ( evtrack.org/review.php ), can be described as "academic" exosomes research, quite a reference value for learning.



Detailed interpretation can be clicked: This Cell article tells you how to study exosome miRNAs


4. Nature: Hypothalamic exocytic miRNA delays aging

Corresponding author: Cai Dongsheng

Author unit: American Einstein College of Medicine

PMID: 28746310


Highlights:

By stimulating the loss of mouse hypothalamic neural stem cells (htNSC), the team observed that the mice developed symptoms of aging, or shortened the life cycle; while transplanting healthy cells to middle-aged mice, the aging rate slowed down, mice Extended life. Interestingly, the study also showed that the miRNA carried by exosomes can partially regulate the anti-aging effect of htNSC and play a corresponding role after htNSC enters cerebrospinal fluid. The results of this study represent a huge breakthrough in the field of anti-aging physiological mechanisms, bringing more promising anti-aging therapies, and exosomes is expected to shine in it.


5.Cell: Exosomal RNA promotes tumor growth and metastasis

Corresponding author: Andy J. Minn

Author unit: University of Pennsylvania

PMID: 28709002


Highlights:

This study found that exosomes is involved in a very specific mechanism of tumor development: in most tumor samples, there is no viral infection; but tumors carrying antiviral signals (ISG, interferon-stimulated genes) are more aggressive, For example, triple negative breast cancer invasive cases. How do tumor cells make normal cells react antivirally? Studies have shown that tumor cells stimulate fibroblasts to release exosomes containing terminally exposed RN7SL1 (which is very similar to viral RNA). When the recipient cells absorb this exosomes, they will mistakenly believe that they are infected with the virus, normal inflammation. The response will be disturbed, and the exposed RN7SL1 in exosomes acts as a DAMP signal to activate RIG-I of breast cancer, ultimately achieving tumor growth and drug resistance.

The more important significance of this study is that RN7SL1 in exosomes secreted by tumor patients is expected to be a biomarker for inflammation and poor prognosis, and even a therapeutic target. At the same time, it also revealed that exosomes researchers, in addition to small RNA, other types of RNA in exosomes have potential research significance.



6.Cell: exosome confers adaptive antiviral immunity to Drosophila

Corresponding author: Raul Andino

Author unit: University of California

PMID: 28884413


Highlights:

Exosomes has a role to play in the role of diseases such as tumors. The function of immunity has always been a hot spot for scientists. The relationship with viruses is also very delicate. It is sometimes used by viruses and sometimes against viruses.

We already know that arthropods can inhibit viral replication and resist viruses through RNA interference mechanisms. In this study, an anti-viral adaptive immunity study was carried out using the model animal of the innate immune research, Drosophila, and it was found that after infection by the virus, the blood cells will use the dsRNA of the infected cells as a template to perform reverse transcription and produce a virus-derived source. Complementary DNA (vDNA), which in turn produces viral siRNA (vsRNA) with vDNA as a template. So how do these vsRNAs that mediate systemic immunity spread effectively? The researchers found the answer: delivery through exosomes. More interestingly, these blood cells vs. exosomes extracted from infected flies were injected into uninfected fruit flies and found that these exosomes confer passive immunity to the recipient Drosophila against the same virus! This is the first time scientists have discovered that Drosophila immune cells use an extracellular vesicle containing vsRNA for adaptive antiviral responses. At this point, the immune mechanism of insects is similar to that of vertebrates.


7. Nucleic Acids Research: exoRBase: Exosomal Long-Chain RNA Database

Corresponding author: Huang Shenglin

Author unit: Fudan University


Highlights:

On the basis of the previous period, Huang Shenglin's research team improved and improved the high-throughput sequencing method of long-chain RNA of blood exosomes. In 2015, through the sequencing analysis of normal human and different diseases exosomal RNA, it was found for the first time that blood exosomes existed. Tens of thousands of circular RNAs; and in 2017 they published a database of various long-chain RNAs (mRNA, lncRNA and circRNA) specifically developed for exosomes: exoRBase ( exoRBase.org ).

exoRBase included a total of 58,330 circRNAs, 15,501 lncRNAs, and 18,333 mRNAs from 92 serum exosomes RNA-seq sequencing samples. The authors also obtained tissue-specific RNA expression profiles based on the GTEx project and analyzed the tissue sources of related RNA molecules.



The exoRBase database provides a very valuable information platform for exosomes research, as well as a data download and upload window. It is a very good exosome research tool.


Summary class

- systematically understand the progress of the field through reviews


8. Nature Rev Clin Oncol: Liquid biopsy and tumor

Corresponding author: Alberto Bardelli

Author unit: Italy IRCCS

PMID: 28252003


Highlights:

This review summarizes how different liquid biopsies such as ctDNA, CTC, and exosomes should be better applied to patient care and even clinical practice, with a focus on ctDNA, which the authors believe is theoretically the most cutting-edge method in the clinic. .

9. Nature Rev Microbiol: The goods and functions of the virus that affect extracellular vesicles

Corresponding author: Nancy Raab-Traub

Author: University of North Carolina

PMID: 28649136


Hightlights:

Extracellular vesicles (EV) or exosomes produced after viral infection of cells can mediate communication between cells that have been infected and not infected with the virus. Studies have shown that viruses (especially oncogenic viruses, viruses that cause chronic diseases) can regulate the production and cargo of EV: miRNAs, proteins, and even whole virions of the virus can be loaded into the EV, thereby affecting the immune system against the virus. Identify, or regulate, adjacent cells. This review summarizes which EV extraction method products are suitable for virus co-culture experiments; how to isolate virions and EVs of similar size; some known viral EV marker proteins. In addition, it is emphasized that in the process of virus infection, some viruses can use EV to promote their own replication in target cells, some viruses will be restricted by EV replication; and discuss the molecular mechanism behind this, the final results of the host and future diagnostic applications. .



to sum up

From the significant advances in exosome research last year, miRNAs in exosomes are still important functional molecules for their function; in addition, other types of RNA molecules are also emerging, and have the research significance of excavating potential mechanisms. These studies not only make us more and more aware of the occurrence and development of other diseases such as tumors, but also illuminate more clinical application prospects in the future. In 2018, we expect that exosomes will bring us more surprises.