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1.
BMC Cancer ; 24(1): 166, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308235

RESUMO

Osteosarcoma (OS) is a highly malignant tumor, and its dysregulated lipid metabolism is associated with tumorigenesis and unfavorable prognosis. Interestingly, long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of lipid metabolism, exerting notable impacts on tumor proliferation. Nevertheless, the involvement of RPARP-AS1, a novel lipid metabolism-associated lncRNA, remains unexplored in the context of OS. This study aims to identify functionally relevant lncRNAs impacting OS proliferation and lipid metabolism and seeks to shed light on the upstream regulatory mechanisms governing lipogenic enzyme activity. Based on comprehensive bioinformatic analysis and the establishment of a risk model, we identified seven lncRNAs significantly associated with clinical characteristics and lipid metabolism-related genes in patients with OS. Among these, RPARP-AS1 was selected for in-depth investigation regarding its roles in OS proliferation and lipid metabolism. Experimental techniques including RT-qPCR, Western blot, cell viability assay, assessment, and quantification of free fatty acids (FFAs) and triglycerides (TGs) were utilized to elucidate the functional significance of RPARP-AS1 in OS cells and validate its effects on lipid metabolism. Manipulation of RPARP-AS1 expression via ectopic expression or siRNA-mediated knockdown led to alterations in epithelial-mesenchymal transition (EMT) and expression of apoptosis-associated proteins, thereby influencing OS cell proliferation and apoptosis. Mechanistically, RPARP-AS1 was found to augment the expression of key lipogenic enzymes (FABP4, MAGL, and SCD1) and potentially modulate the Akt/mTOR pathway, thereby contributing to lipid metabolism (involving alterations in FFA and TG levels) in OS cells. Collectively, our findings establish RPARP-AS1 as a novel oncogene in OS cells and suggest its role in fostering tumor growth through the enhancement of lipid metabolism.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Metabolismo dos Lipídeos/genética , Linhagem Celular Tumoral , MicroRNAs/genética , Proliferação de Células/genética , Osteossarcoma/patologia , Neoplasias Ósseas/patologia , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética
2.
Angew Chem Int Ed Engl ; 60(11): 5843-5847, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33325578

RESUMO

Reported herein is the pyrazole-directed iridium-catalyzed enantioselective borylation of unbiased methylene C-H bonds at the position ß to a nitrogen center. The combination of a chiral bidentate boryl ligand, iridium precursor, and pyrazole directing group was responsible for the high regio- and enantioselectivity observed. The method tolerated a vast array of functional groups to afford the corresponding C(sp3 )-H functionalization products with good to excellent enantioselectivity.

3.
J Am Chem Soc ; 142(28): 12062-12068, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32597651

RESUMO

We herein report an iridium-catalyzed enantioselective α-C(sp3)-H borylation of a wide range of azacycles. The combination of an iridium precursor and a chiral bidentate boryl ligand has been shown to effectively differentiate enantiotropic methylene C-H bonds from a single carbon center, affording a variety of synthetically useful azacycles from readily available starting materials with good to excellent enantioselectivities.

4.
RSC Adv ; 11(10): 5487-5490, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35423099

RESUMO

We herein report a ligand-free Ir-catalyzed C-H borylation of N-acyl protected indoles. This simple protocol could tolerate a variety of functional groups, affording C3 borylated indoles in good yields with excellent regioselectivities. We also demonstrated that the current method is amenable to gram-scale borylation and the C-B bonds could be easily converted to C-C and C-heteroatom bonds.

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