ELIZA

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403337 occurrences (No.43 in the rank) during 5 years in the PubMed. [cache]

297) TCGA has recently revealed that a hypoxia gene signature is associated with poor UM patient prognosis.

--- ABSTRACT ---

PMID:34218269 DOI:10.1038/s41388-021-01919-x

2021 Oncogene

* Targeting HIF-activated collagen prolyl 4-hydroxylase expression disrupts collagen deposition and blocks primary and metastatic uveal melanoma growth.

- Uveal melanoma (UM) is the most prevalent primary intraocular malignancy in adults, and patients that develop metastases (~50%) survive <1 year, highlighting the urgent need for new therapies. TCGA has recently revealed that a hypoxia gene signature is associated with poor UM patient prognosis. Here we show that expression of hypoxia-regulated collagen prolyl-4-hydroxylase genes P4HA1 and P4HA2 is significantly upregulated in UM patients with metastatic disease and correlates with poor prognosis, suggesting these enzymes might be key tumor drivers. We targeted hypoxia-induced expression of P4HA1/2 in UM with KCN1, a hypoxia inducible factor-1 (HIF-1) pathway inhibitor and found potent inhibition of primary and metastatic disease and extension of animal survival, without overt side effects. At the molecular level, KCN1 antagonized hypoxia-induced expression of P4HA1 and P4HA2, which regulate collagen maturation and deposition in the extracellular matrix. The treatment decreased prolyl hydroxylation, induced proteolytic cleavage and rendered a disordered structure to collagen VI, the main collagen produced by UM, and reduced UM cell invasion. Together, these data demonstrate that extracellular collagen matrix formation can be targeted in UM by inhibiting hypoxia-induced P4HA1 and P4HA2 expression, warranting further development of this strategy in patients with uveal melanoma.

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(1)132 expression	(14)5 drive	(27)3 duplications	(40)2 for
(2)14 null	(15)5 editing	(28)3 ontology	(41)2 from
(3)12 expression,	(16)5 mutations	(29)3 signature	(42)2 fusion,
(4)11 and	(17)5 of	(30)3 to	(43)2 have
(5)10 encoding	(18)5 regulation	(31)3 which	(44)2 is
(6)10 set	(19)4 networks	(32)2 analysis	(45)2 ontologies
(7)8 in	(20)4 regulatory	(33)2 are	(46)2 or
(8)8 that	(21)4 silencing	(34)2 assay,	(47)2 pathways
(9)7 1	(22)4 transcription	(35)2 called	(48)2 profile
(10)6 interaction	(23)4 transfer	(36)2 cluster	(49)2 promoter
(11)6 therapy	(24)3 1/itaconate	(37)2 delivery	(50)2 sequencing
(12)6 was	(25)3 co-expression	(38)2 detection	(51)2 sets
(13)5 Expression	(26)3 coexpression	(39)2 expressions	(52)2 transcripts

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--- WordNet output for gene --- =>遺伝子 Overview of noun gene The noun gene has 1 sense (no senses from tagged texts) 1. gene, cistron, factor -- ((genetics) a segment of DNA that is involved in producing a polypeptide chain; it can include regions preceding and following the coding DNA as well as introns between the exons; it is considered a unit of heredity; "genes were formerly called factors") --- WordNet end ---