MicroRNA-375 plays a dual role in prostate carcinogenesis

Background: Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis. Results: MicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, as well as with regional lymph nodes metastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay. Conclusions: A dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.

MicroRNA-375 plays a dual role in prostate carcinogenesis

Background: Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis. Results: MicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, aswellaswithregionallymph nodesmetastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay. Conclusions: A dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.

375 vuotta maanmittausta Suomessa

Kirjallisuusarvostelu

Français 375

Contient : 1° « Apocalipsis », en latin ; 2° Explication de l'Apocalypse, en français ; 3° Prophétie de la sibylle Tiburnica ; 4° « Le Livre de Seneke », traité de Moralité ; 5° Sommaires en vers des poëmes contenus dans le volume, par « PEROS DE NEELE » ; 6° « Li Sieges de Tebes, et d'Ethioclet et de Pollinices » ; 7° Le Roman « de Troies », de « BENEOIT DE SAINTE MORE » ; 8° « Li Sieges d'Ataines », ou Roman d'Athis et Profilias, par « ALEXANDRE » ; 9° « Li Dit JEHAN BODEL », ou le Congé ; 10° Le Roman d'Alixandre, de « LAMBERT LE TORT » et « ALEXANDRE » [de Bernay] ; 11° La Signification de la mort d'Alexandre [de PIERRE DE SAINT-CLOUD] ; 12° La Vengeance d'Alexandre [de GUI, de Cambrai] ; 13° « Des Dus de Normendie », généalogie des comtes de Boulogne ; 14° Le Roman de Rou [de WACE] ; 15° Le Roman « del roi Guillaume d'Engleterre », de « CRESTHEN » [de Troyes] ; 16° Le Roman « de Floire et Blanceflor » ; 17° Le Roman « de Blancandin » ; 18° Le Roman « de Cliget », de « CRESTHEN » [de Troyes] ; 19° « D'Erec et.d'Enide », de « CRESTHEN » [de Troyes] ; 20° « De le Viellete lixun » ; 21° « D'Ysle et de Galeron », de « GAUTIER, d'Arras » ; 22° « De Theophilus » [de GAUTIER, de Coincy] ; 23° « D'Amaldas et de Ydoine » ; 24° « De le Castelaine de Vergi » ; 25° Prose « de saint Estevene », avec la notation ; 26° « Des Vers de le mort », trois cent treize douzains ; 27° « Li Loenge Nostre Dame » ; 28° « De le Viellete » ; 29° Neuf Miracles de Notre-Dame, savoir ; 1 « D'un abé por cui Nostre Dame ouvra en mer » ; 2 « De l'enfant qui son pain offri à l'enfant l'ymage Nostre Dame » ; 3 « D'un moine » ; 4 « D'un clerc » ; 5 « D'un soucrestain » ; 6 « De le soucretaine » ; 7 « D'une grosse feme » ; 8 « D'une ymage Nostre Dame » ; 9 « De la Nativité Nostre Dame »

Les diplômés – no 375, automne 1991

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MiR-375 is essential for human spinal motor neuron development and may be involved in motor neuron degeneration

The transcription factor REST is a key suppressor of neuronal genes in non-neuronal tissues. REST has been shown to suppress pro-neuronal microRNAs in neural progenitors indicating that REST-mediated neurogenic suppression may act in part via microRNAs. We used neural differentiation of Rest-null mouse ESC to identify dozens of microRNAs regulated by REST during neural development. One of the identified microRNAs, miR-375, was upregulated during human spinal motor neuron development. We found that miR-375 facilitates spinal motor neurogenesis by targeting the cyclin kinase CCND2 and the transcription factor PAX6. Additionally, miR-375 inhibits the tumor suppressor p53 and protects neurons from apoptosis in response to DNA damage. Interestingly, motor neurons derived from a spinal muscular atrophy patient displayed depressed miR-375 expression and elevated p53 protein levels. Importantly, SMA motor neurons were significantly more susceptible to DNA damage induced apoptosis suggesting that miR-375 may play a protective role in motor neurons.

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 375 - Verlagsvertrag zwischen der Autorin Johanna Schopenhauer und den beiden Verlagen Johann David Sauerländer und Friedrich Arnold Brockhaus

u.a.: Mitunterzeichnerin Adele Schopenhauer;