Therapeutic roles of mesenchymal stem cell-derived extracellular vesicles in cancer

Journal of Hematology & Oncology, Год журнала: 2021, Номер 14(1)

Опубликована: Сен. 3, 2021

Abstract Extracellular vesicles (EVs) are cell-derived membrane structures enclosing proteins, lipids, RNAs, metabolites, growth factors, and cytokines. EVs have emerged as essential intercellular communication regulators in multiple physiological pathological processes. Previous studies revealed that mesenchymal stem cells (MSCs) could either support or suppress tumor progression different cancers by paracrine signaling via MSC-derived EVs. Evidence suggested mimic their parental cells, possessing pro-tumor anti-tumor effects, inherent tropism. Therefore, can be a cell-free cancer treatment alternative. This review discusses insights regarding EVs' roles summarizes bioengineered EVs’ applications safe versatile agent delivery platforms. Meanwhile, current hurdles of moving from bench to bedside also discussed.

Язык: Английский

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Osteosarcoma and Metastasis

Frontiers in Oncology, Год журнала: 2021, Номер 11

Опубликована: Дек. 10, 2021

Osteosarcoma is the most common primary bone malignancy in adolescents. Its high propensity to metastasize leading cause for treatment failure and poor prognosis. Although research of osteosarcoma has greatly expanded past decades, knowledge new therapy strategies targeting metastatic progression remain sparse. The prognosis patients with metastasis still unsatisfactory. There resonating urgency a thorough deeper understanding molecular mechanisms underlying develop innovative therapies metastasis. Toward goal elaborating characteristics biological behavior osteosarcoma, it essential combine diverse investigations that are performed at molecular, cellular, animal levels from basic clinical translation spanning chemical, physical sciences, biology. This review focuses on process, regulatory networks involving key molecules signaling pathways, role microenvironment, osteoclast, angiogenesis, metabolism, immunity, noncoding RNAs aim this provide an overview current advances, hope discovery druggable targets promising thus overcome impasse.

Язык: Английский

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Investigating the role of exosomal long non-coding RNAs in drug resistance within female reproductive system cancers

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Янв. 24, 2025

Exosomes, as key mediators of intercellular communication, have been increasingly recognized for their role in the oncogenic processes, particularly facilitating drug resistance. This article delves into emerging evidence linking exosomal lncRNAs to modulation resistance mechanisms cancers such ovarian, cervical, and endometrial cancer. It synthesizes current research findings on how these influence cancer cell survival, tumor microenvironment, chemotherapy efficacy. Additionally, review highlights potential therapeutic strategies targeting lncRNAs, proposing a new frontier overcoming By mapping interface resistance, this aims provide comprehensive understanding that could pave way innovative treatments improved patient outcomes female reproductive system cancers.

Язык: Английский

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Bone marrow mesenchymal stem cell-derived exosomal miR-206 inhibits osteosarcoma progression by targeting TRA2B

Cancer Letters, Год журнала: 2020, Номер 490, С. 54 - 65

Опубликована: Июль 16, 2020

Язык: Английский

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Mesenchymal stem cell-derived extracellular vesicles: a possible therapeutic strategy for orthopaedic diseases: a narrative review.

PubMed, Год журнала: 2022, Номер 3(3), С. 175 - 187

Опубликована: Янв. 1, 2022

Accumulating evidence suggests that the therapeutic role of mesenchymal stem cells (MSCs) in bone diseases is closely related to paracrine-generated extracellular vesicles (EVs). MSC-derived EVs (MSC-EVs) carry proteins, nucleic acids, and lipids space affect microenvironment. They have similar biological functions MSCs, such as ability repair organ tissue damage. In addition, MSC-EVs also advantages long half-life, low immunogenicity, attractive stability, pass through blood-brain barrier, demonstrate excellent performance with potential practical applications diseases. this review, we summarise current mechanisms osteoporosis, osteoarthritis, tumours, osteonecrosis femoral head, fractures, well development combined materials science field orthopaedics. Additionally, explore critical challenges involved clinical application orthopaedic

Язык: Английский

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lncRNA PVT1: a novel oncogene in multiple cancers

Cellular & Molecular Biology Letters, Год журнала: 2022, Номер 27(1)

Опубликована: Окт. 4, 2022

Abstract Long noncoding RNAs are involved in epigenetic gene modification, including binding to the chromatin rearrangement complex pre-transcriptional regulation and promoters expression regulation, as well acting microRNA sponges control messenger RNA levels post-transcriptional regulation. An increasing number of studies have found that long plasmacytoma variant translocation 1 (PVT1) plays an important role cancer development. In this review a large on PVT1, we PVT1 is closely related tumor onset, proliferation, invasion, epithelial–mesenchymal transformation, apoptosis, poor prognosis radiotherapy chemotherapy resistance some cancers. This comprehensively describes various cancers presents novel approaches diagnosis treatment cancer.

Язык: Английский

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Biogenesis, Composition and Potential Therapeutic Applications of Mesenchymal Stem Cells Derived Exosomes in Various Diseases

International Journal of Nanomedicine, Год журнала: 2023, Номер Volume 18, С. 3177 - 3210

Опубликована: Июнь 1, 2023

Abstract: Exosomes are nanovesicles with a wide range of chemical compositions used in many different applications. Mesenchymal stem cell-derived exosomes (MSCs-EXOs) spherical vesicles that have been shown to mediate tissue regeneration variety diseases, including neurological, autoimmune and inflammatory, cancer, ischemic heart disease, lung injury, liver fibrosis. They can modulate the immune response by interacting effector cells due presence anti-inflammatory compounds involved intercellular communication through various types cargo. MSCs-EXOs exhibit cytokine storm-mitigating properties COVID-19. This review discussed potential function diseases notably epileptic encephalopathy Parkinson's angiogenesis, inflammatory diseases. We provided an overview exosome biogenesis factors regulate biogenesis. Additionally, we highlight functions use treatment disease Finally, covered strategies challenges MSCs-EXOs. discuss conclusion future perspectives Keywords: extracellular vesicle, biogenesis, mesenchymal cells, exosomes, angiogenesis

Язык: Английский

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Nanotherapeutic approaches for delivery of long non-coding RNAs: an updated review with emphasis on cancer

Nanoscale, Год журнала: 2024, Номер 16(8), С. 3881 - 3914

Опубликована: Янв. 1, 2024

The long noncoding RNAs (lncRNAs) comprise a wide range of RNA species whose length exceeds 200 nucleotides, which regulate the expression genes and cellular functions in organisms.

Язык: Английский

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Regulation of bone homeostasis: signaling pathways and therapeutic targets

MedComm, Год журнала: 2024, Номер 5(8)

Опубликована: Июль 24, 2024

As a highly dynamic tissue, bone is continuously rebuilt throughout life. Both formation by osteoblasts and resorption osteoclasts constitute reconstruction homeostasis. The equilibrium of homeostasis governed many complicated signaling pathways that weave together to form an intricate network. These coordinate the meticulous processes resorption, ensuring structural integrity vitality skeletal system. Dysregulation homeostatic regulatory network contributes development progression diseases. Significantly, imbalanced further disrupts triggers cascade reaction exacerbates disease engenders deleterious cycle. Here, we summarize influence on homeostasis, elucidating interplay crosstalk among them. Additionally, review mechanisms underpinning imbalances across diverse landscapes, highlighting current prospective therapeutic targets clinical drugs. We hope this will contribute holistic understanding molecular sustaining which are promising research shed light targeted

Язык: Английский

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Exosomal Long Non-coding RNAs: Emerging Players in the Tumor Microenvironment

Molecular Therapy — Nucleic Acids, Год журнала: 2020, Номер 23, С. 1371 - 1383

Опубликована: Окт. 4, 2020

Recent advances in exosome biology have uncovered a significant role of exosomes cancer and make them determining factor intercellular communication. Exosomes are types extracellular vesicles that involved the communication between cells by exchanging various signaling molecules surrounding cells. Among molecules, long non-coding RNAs (lncRNAs), type RNA having size more than 200 nt length lacking protein-coding potential, emerged as crucial regulators Tumor-derived containing lncRNAs, known exosomal reprogram microenvironment regulating numerous cellular functions, including regulation gene transcription favors growth progression, thus significantly biological effects exosomes. In addition, deregulated expression lncRNAs is found human cancers serves diagnostic biomarker to predict type. The present review discusses crosstalk tumor microenvironment. Furthermore, we also discuss involvement within favoring growth, metabolic reprogramming cells, tumor-supportive autophagy. Therefore, can be used therapeutic target treatment cancers. single-membrane about 30–150 nm diameter formed from endocytic vesicles.1Zaborowski M.P. Balaj L. Breakefield X.O. Lai C.P. Extracellular vesicles: composition, relevance, methods study.Bioscience. 2015; 65: 783-797Crossref PubMed Scopus (244) Google Scholar,2Soares Martins T. Catita J. Rosa I. A B da Cruz E Silva O. Henriques A.G. Exosome isolation distinct biofluids using precipitation column-based approaches.PLoS ONE. 2018; 13: e0198820Crossref (76) Scholar During endocytosis, material surrounded an area plasma membrane, which invaginates forms vesicle ingested material.3Kumari S. Mg Mayor Endocytosis unplugged: multiple ways enter cell.Cell Res. 2010; 20: 256-275Crossref (255) Once internalized, this membrane-bound fuses with early endosome, sorting station for cargo mainly proteins lipids.4Jovic M. Sharma Rahajeng Caplan endosome: busy at crossroads.Histol. Histopathol. 25: 99-112PubMed Early endosomes highly dynamic form either multivesicular bodies (MVBs), called late endosomes, or recycling part tubulovesicular system.5Piper R.C. Katzmann D.J. Biogenesis function bodies.Annu. Rev. Cell Dev. Biol. 2007; 23: 519-547Crossref (431) Scholar,6Goldenring J.R. Recycling endosomes.Curr. Opin. 35: 117-122Crossref (69) This system transports Golgi network, endoplasmic reticulum. membrane via slow pathway.7Sheff D.R. Daro E.A. Hull Mellman receptor pathway contains two populations different functions.J. 1999; 145: 123-139Crossref (356) Scholar,8Sönnichsen B. De Renzis Nielsen E. Rietdorf Zerial Distinct domains on visualized multicolor imaging Rab4, Rab5, Rab11.J. 2000; 149: 901-914Crossref (747) Cargoes delivered directly fast Scholar,9Taguchi Emerging roles endosomes.J. Biochem. 2013; 153: 505-510Crossref (39) transport network reticulum retrograde pathway.10Pfeffer S.R. Multiple routes protein trans network.FEBS Lett. 2009; 583: 3811-3816Crossref (53) Most recycled back cell surface receptors, adhesion ion channels, polarization,11Grant B.D. Donaldson J.G. Pathways mechanisms recycling.Nat. Mol. 10: 597-608Crossref (846) whereas there wide range functionally diverse utilize pathway.12Johannes Popoff V. Tracing route trafficking.Cell. 2008; 135: 1175-1187Abstract Full Text PDF (264) Late fuse lysosomes endolysosomes, resulting degradation their through lysosomal hydrolases. When mature into they accumulate small inside lumen inward budding contain proteins, lipids, nucleic acids specifically sorted.13Huotari Helenius A. Endosome maturation.EMBO 2011; 30: 3481-3500Crossref (1148) presence intraluminal (ILVs) gives appearance. often referred MVBs.14Piper Luzio J.P. endosomes: partitioning bodies.Traffic. 2001; 2: 612-621Crossref (154) Not all ILVs destined degradation; some secreted out space due fusion MVBs regulated process. These small, They other similar-sized (EVs) microvesicles, ectosomes, apoptotic based origin, structure, specific markers membranes.15Holme P.A. Solum N.O. Brosstad F. Røger Abdelnoor Demonstration platelet-derived microvesicles blood patients activated coagulation fibrinolysis filtration technique western blotting.Thromb. Haemost. 1994; 72: 666-671Crossref (89) Scholar, 16Hess C. Sadallah Hefti Landmann R. Schifferli J.A. Ectosomes released neutrophils specialized functional units.J. Immunol. 163: 4564-4573PubMed 17Kerr J.F. Wyllie A.H. Currie A.R. Apoptosis: basic phenomenon wide-ranging implications tissue kinetics.Br. Cancer. 1972; 26: 239-257Crossref Microvesicles, originate irregular shapes, endosomal cup-shaped, homologous, carry markers, Alix, TSG101, tetraspanins CD63, CD9, CD81 (Figure 1).18Théry Zitvogel Amigorena Exosomes: biogenesis function.Nat. 2002; 569-579Crossref 19Théry Boussac Véron P. Ricciardi-Castagnoli Raposo G. Garin Proteomic analysis dendritic cell-derived exosomes: subcellular compartment vesicles.J. 166: 7309-7318Crossref 20Simpson R.J. Lim J.W. Moritz R.L. Mathivanan proteomic insights potential.Expert Proteomics. 6: 267-283Crossref (655) 21Kowal Arras Colombo Jouve Morath Primdal-Bengtson Dingli Loew D. Tkach Théry comparison defines novel characterize heterogeneous subtypes.Proc. Natl. Acad. Sci. USA. 2016; 113: E968-E977Crossref (1184) term was first coined 1987 Johnstone et al.22Johnstone R.M. Adam Hammond Orr Turbide Vesicle formation during reticulocyte maturation. Association activities (exosomes).J. Chem. 1987; 262: 9412-9420Abstract sheep reticulocytes, where reported secretion loss transferrin small-sized (50 nm) maturation erythrocytes. group harvested these reticulocytes centrifugation 100,000 × g 90 min. lysed contained had many were characteristic reduced absent include acetylcholinesterase, cytochalasin binding (glucose transporter), nucleoside (i.e., Na+-independent amino acid transport, suggesting performing maturation.22Johnstone Since then, been discovered most types, such immune (T lymphocytes,23Wahlgren Karlson Tde.L. Glader Telemo Valadi H. Activated T secrete participate IL-2 mediated response signaling.PLoS 2012; 7: e49723Crossref (0) lymphocytes,24Wubbolts Leckie R.S. Veenhuizen P.T. Schwarzmann Möbius W. Hoernschemeyer Slot Geuze H.J. Stoorvogel biochemical analyses Potential body formation.J. 2003; 278: 10963-10972Abstract (612) natural killer cells,25Lugini Cecchetti Huber Luciani Macchia Spadaro Paris Abalsamo Colone Molinari al.Immune surveillance properties NK exosomes.J. 189: 2833-2842Crossref (195) cells,26Segura Mature strong ability induce antigen-specific effector responses.Blood Cells Dis. 2005; 89-93Crossref (167) mast cells27Skokos Le Panse Villa Rousselle J.C. Peronet David Namane Mécheri Mast cell-dependent lymphocyte activation immunologically active 868-876Crossref Scholar), cells,28Bae Brumbaugh Bonavida derived cancerous non-cancerous regulate anti-tumor microenvironment.Genes 9: 87-100Crossref (33) embryonic29Song Y.H. Shao Zhang Y. Zhou Liu Pan X. Geng Y.J. Yu X.Y. Li embryonic stem potential cardiovascular diseases.Adv. Exp. Med. 2017; 998: 187-206Crossref (5) mesenchymal cells,30Yin K. Wang Zhao stem/stromal cells: new paradigm.Biomark. 2019; 8Crossref (36) adipocytes,31Deng Z.B. Poliakov Hardy R.W. Clements Xiang Zhuang al.Adipose exosome-like mediate macrophage-induced insulin resistance.Diabetes. 58: 2498-2505Crossref (212) glial cells,32Frühbeis Fröhlich Kuo W.P. Krämer-Albers E.M. mediators neuron-glia communication.Front. Cell. Neurosci. 182Crossref (204) fluids blood, urine, semen, breast milk.33Keller Ridinger Rupp A.K. Janssen Altevogt Body fluid template clinical diagnostics.J. Transl. 86Crossref (396) perform cell-to-cell communications delivery DNA, RNA, recipient cells,34Bang Thum players cell-cell communication.Int. 44: 2060-2064Crossref (251) regulation,35Li X.B. Z.R. Schluesener Xu S.Q. Role regulation.J. 2006; 364-375Crossref selective macromolecules maturation,22Johnstone development progression diseases, cancer,36Azmi A.S. Bao Sarkar F.H. development, metastasis, drug resistance: comprehensive review.Cancer Metastasis 32: 623-642Crossref (619) diabetes,31Deng cardiovascular37Bellin Gardin Ferroni Chachques Rogante Mitrečić Ferrari Zavan diseases: complex world full hope.Cells. 8: 166Crossref neurodegenerative38Sardar Sinha Ansell-Schultz Civitelli Hildesjö Larsson Lannfelt Ingelsson Hallbeck Alzheimer's disease pathology propagation toxic amyloid-beta oligomers.Acta Neuropathol. 136: 41-56Crossref (106) diseases. Cancer-derived vital survival play important modulation favor metastasis.39Zhang immunity.Biochim. Biophys. Acta 1871: 455-468Crossref (37) Scholar,40Wortzel Dror Kenific C.M. Lyden Exosome-mediated metastasis: distance.Dev. 49: 347-360Abstract (142) Many help communicate normal stromal vascular endothelial cancer-associated fibroblasts (CAFs). helps establishment favorable microenvironment, promotes escape,41Kim D.H. Kim Choi S.Y. Lee J.E. Sung K.J. Pack C.G. Jung M.K. Han al.Exosomal PD-L1 escape non-small lung cancer.Exp. 51: 1-13Google invasion,42Cai Z. Yang Jiang Q. Cao promote invasion Fas pathway.J. 188: 5954-5961Crossref migration,43Harada Yamamoto Kishida Awada Takao Kikuchi Wnt5b-associated migration proliferation.Cancer 108: 42-52Crossref premetastatic niches secondary organs.44Feng Dean D.C. Hornicek F.J. Shi Duan pre-metastatic niche ovarian cancer.Mol. 18: 124Crossref (42) suppress receptors (TCRs) inhibit proliferation CD8+ cytotoxic lymphocytes (CTLs) kill them. Coincubation isolated lines, head neck squamous carcinoma PCL-13 melanoma line Mel-SW, inhibits proliferation.45Wieckowski E.U. Visus Szajnik Szczepanski M.J. Storkus W.J. Whiteside T.L. regulatory expansion apoptosis tumor-reactive lymphocytes.J. 183: 3720-3730Crossref (302) Jurkat line) coincubated undergo fragmented DNA,45Wieckowski suppression cancer-derived stem-like brain tumor-initiating (BTICs) high amounts matrix tenascin-C (TNC) exosomes, activity α5β1 αvβ6 integrins blocks TCR signaling.46Mirzaei Dzikowski Rawji K.S. Khan Faissner Bose Yong V.W. Brain export associated activity.OncoImmunology. e1478647Crossref TNC glioblastoma immunosuppressive phenotype worse overall patients.46Mirzaei Scholar,47Xia Lal Tung Goodwin C.R. Laterra Tumor negatively regulates proliferation.Neuro-oncol. 507-517Crossref (61) Another pro-tumorigenic programmed death-ligand 1 (PD-L1), binds death-1 (PD-1) its effectively protects surveillance.48Yang C.W. Chan L.C. Wei Hsu J.M. Xia Cha J.H. Hou J.L. Sun Hung M.C. Exosomal harbors defense killing growth.Cell 28: 862-864Crossref (84) culture supernatants lines MDA-MB-231 (human) 4T1 (mouse mammary cells), colon RKO, HCC827 functions inhibiting CD3/CD28-triggered pathway.48Yang Interestingly, transfer low no expression, tumor-derived enhancing response.48Yang Moreover, knockdown mouse injected mice shows regression, tumors activity.48Yang Except enriched metabolites origin functions.18Théry content has gained considerable attention recent years promoting microenvironment,49Challagundla K.B. Wise P.M. Neviani Chava Murtadha Kennedy Ivan Vannini al.Exosome-mediated microRNAs neuroblastoma resistance chemotherapy.J. Cancer Inst. 107: djv135Crossref (170) Scholar,50Liu Peng Chen cancer.Int. 3884Crossref (14) progression,51Yoshii Hayashi Iijima Inoue Kimura Sakatani Nagai Fujinaga Hiyama Kodama suppressing fibroblast TP53 expression.Cancer 110: 2396-2407Crossref (16) angiogenesis,52Hu H.Y. C.H. H.H. S.Z. W.Y. miR-1229 colorectal angiogenesis targeting HIPK2.Int. Macromol. 132: 470-477Crossref (18) metastasis53Chen Luo He Kong Zhong Huang noncoding LNMAT2 lymphatic metastasis bladder cancer.J. Clin. Invest. 2020; 130: 404-421Crossref (35) use types.54Chen Rai Suwakulsiri Izumikawa Ishikawa Greening D.W. Takahashi N. Simpson shed microvesicle microRNA signatures reveal cancer.PLoS 14: e0210003PubMed 55Chen Wu Ding Jiao Zhan An Upregulated exosomic miR-23b-3p plays pancreatic cancer.Oncol. Rep. 38: 2182-2188Crossref (24) 56Hannafon B.N. Trigoso Y.D. Calloway C.L. Lum Welm A.L. Z.J. Blick K.E. Dooley W.C. W.Q. Plasma indicative cancer.Breast 90Crossref (199) detected coding mRNAs circular RNAs, (miRNAs), (lncRNAs). Non-coding (ncRNAs) represent large segment genome do not code major contributors RNA-mediated carcinogenesis. review, will focus therapy. proteins. Only few (less 2%) translated mRNAs, even though 90% transcribed.57Lander E.S. Linton L.M. Birren Nusbaum Zody Baldwin Devon Dewar Doyle FitzHugh al.International Human Genome Sequencing ConsortiumInitial sequencing genome.Nature. 409: 860-921Crossref (16016) 58Venter Adams M.D. Myers E.W. P.W. Mural Sutton G.G. Smith H.O. Yandell Evans C.A. Holt R.A. al.The sequence genome.Science. 291: 1304-1351Crossref (9749) 59Carninci Kasukawa Katayama Gough Frith Maeda Oyama Ravasi Lenhard Wells al.FANTOM ConsortiumRIKEN Exploration Research Group Science (Genome Network Project Core Group)The transcriptional landscape mammalian 309: 1559-1563Crossref (2487) 60Saha Sparks A.B. Rago Akmaev C.J. Vogelstein Kinzler K.W. Velculescu V.E. Using transcriptome annotate genome.Nat. Biotechnol. 508-512Crossref (476) rest transcribed central transcriptional, post-transcriptional, translational levels. divided main groups transcript. There short less 40 length, comprised nt. miRNAs (18–25 length),61Kim Y.K. V.N. Processing intronic microRNAs.EMBO 775-783Crossref (534) interfering (siRNAs, 19–23 length),62Pasquinelli A.E. Ruvkun Control developmental timing targets.Annu. 495-513Crossref (266) Scholar,63Ambros Lavanway Williams Jewell MicroRNAs tiny endogenous elegans.Curr. 807-818Abstract (517) PIWI-interacting (piRNAs, 21–36 length),64Girard Sachidanandam Hannon G.J. Carmell M.A. germline-specific class Piwi proteins.Nature. 442: 199-202Crossref (1056) fragments (tRFs, 17–26 length).65Lee Y.S. Shibata Malhotra Dutta RNAs: tRNA-derived (tRFs).Genes 2639-2649Crossref (560) extensively diversity species, animals,66Lu Progress animals.Yi Chuan. 39: 1054-1065PubMed plants,67Wang H.V. Chekanova Long plants.Adv. 1008: 133-154Crossref (30) bacteria,68Harris K.A. Breaker R.R. Large bacteria.Microbiol. Spectr. 6https://doi.org/10.1128/microbiolspec.RWR-0005-2017Crossref (12) fungi,69Till Mach Mach-Aigner current view yeast filamentous fungi.Appl. Microbiol. 102: 7319-7331Crossref (9) viruses.70Yi Xie Jin virus infection pathogenesis.Front. Biosci. 24: 777-789Crossref (4) primarily classified size, but analysis, further classes.71St Laurent Wahlestedt Kapranov classification.Trends Genet. 31: 239-251Abstract (480) location and, similar polyadenylated, capped, genetic information. However, complexity transcriptome, well-defined rela

Язык: Английский

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