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286534 occurrences (No.87 in the rank) during 5 years in the PubMed. [cache]

384) RTS osteoblast metabolic assays demonstrated elevated mitochondrial respiratory complex I function, increased oxidative phosphorylation (OXPHOS), and increased ATP production.

--- ABSTRACT ---

PMID:34965247 DOI:10.1371/journal.pgen.1009971

2021 PLoS genetics

* Patient-derived iPSCs link elevated mitochondrial respiratory complex I function to osteosarcoma in Rothmund-Thomson syndrome.

- Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma, small stature, skeletal anomalies, sparse brows/lashes, cataracts, and predisposition to cancer. Type 2 RTS patients with biallelic RECQL4 pathogenic variants have multiple skeletal anomalies and a significantly increased incidence of osteosarcoma. Here, we generated RTS patient-derived induced pluripotent stem cells (iPSCs) to dissect the pathological signaling leading to RTS patient-associated osteosarcoma. RTS iPSC-derived osteoblasts showed defective osteogenic differentiation and gain of in vitro tumorigenic ability. Transcriptome analysis of RTS osteoblasts validated decreased bone morphogenesis while revealing aberrantly upregulated mitochondrial respiratory complex I gene expression. RTS osteoblast metabolic assays demonstrated elevated mitochondrial respiratory complex I function, increased oxidative phosphorylation (OXPHOS), and increased ATP production. Inhibition of mitochondrial respiratory complex I activity by IACS-010759 selectively suppressed cellular respiration and cell proliferation of RTS osteoblasts. Furthermore, systems analysis of IACS-010759-induced changes in RTS osteoblasts revealed that chemical inhibition of mitochondrial respiratory complex I impaired cell proliferation, induced senescence, and decreased MAPK signaling and cell cycle associated genes, but increased H19 and ribosomal protein genes. In summary, our study suggests that mitochondrial respiratory complex I is a potential therapeutic target for RTS-associated osteosarcoma and provides future insights for clinical treatment strategies.

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[frequency of next (right) word to demonstrated]

(1)169 that	(11)5 good	(21)3 that,	(31)2 leadership
(2)48 a	(12)5 using	(22)2 altered	(32)2 on
(3)34 the	(13)5 with	(23)2 benefits	(33)2 positive
(4)18 in	(14)4 comparable	(24)2 decreases	(34)2 potential
(5)17 to	(15)4 for	(25)2 elevated	(35)2 robustness
(6)16 by	(16)4 how	(26)2 evidence	(36)2 significantly
(7)9 an	(17)4 its	(27)2 greater	(37)2 similar
(8)8 significant	(18)3 improved	(28)2 higher	(38)2 statistically
(9)7 null	(19)3 no	(29)2 highly	(39)2 successful
(10)7 efficacy	(20)3 several	(30)2 increased	(40)2 survival

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--- WordNet output for demonstrated --- Overview of verb demonstrate The verb demonstrate has 4 senses (first 4 from tagged texts) 1. (24) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested audience; "She shows her dogs frequently"; "We will demo the new software in Washington") 2. (22) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an example, explanation or experiment; "The experiment demonstrated the instability of the compound"; "The mathematician showed the validity of the conjecture") 3. (2) attest, certify, manifest, demonstrate, evidence -- (provide evidence for; stand as proof of; show by one's behavior, attitude, or external attributes; "His high fever attested to his illness"; "The buildings in Rome manifest a high level of architectural sophistication"; "This decision demonstrates his sense of fairness") 4. (1) demonstrate, march -- (march in protest; take part in a demonstration; "Thousands demonstrated against globalization during the meeting of the most powerful economic nations in Seattle") Overview of adj demonstrated The adj demonstrated has 1 sense (first 1 from tagged texts) 1. (1) demonstrated -- (having been demonstrated or verified beyond doubt) --- WordNet end ---