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Detecting the FLJ22447 lncRNA in Ovarian Cancer with Cyclopentane-Modified FIT-PNAs (cpFIT-PNAs).
Mannully, Sheethal Thomas; Mahajna, Rawan; Nazzal, Huda; Maree, Salam; Zheng, Hongchao; Appella, Daniel H; Reich, Reuven; Yavin, Eylon.
Afiliación
  • Mannully ST; Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Hadassah Ein-Kerem, Jerusalem 91120, Israel.
  • Mahajna R; Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Hadassah Ein-Kerem, Jerusalem 91120, Israel.
  • Nazzal H; Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Hadassah Ein-Kerem, Jerusalem 91120, Israel.
  • Maree S; Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Hadassah Ein-Kerem, Jerusalem 91120, Israel.
  • Zheng H; Synthetic Bioactive Molecules Section, Laboratory of Bioorganic Chemistry (LBC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, 8 Center Drive, Room 404, Bethesda, MD 20892, USA.
  • Appella DH; Synthetic Bioactive Molecules Section, Laboratory of Bioorganic Chemistry (LBC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, 8 Center Drive, Room 404, Bethesda, MD 20892, USA.
  • Reich R; Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Hadassah Ein-Kerem, Jerusalem 91120, Israel.
  • Yavin E; Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Hadassah Ein-Kerem, Jerusalem 91120, Israel.
Biomolecules ; 14(6)2024 May 22.
Article en En | MEDLINE | ID: mdl-38927013
ABSTRACT
Ovarian cancer (OC) is one of the most lethal gynecologic cancers that is typically diagnosed at the very late stage of disease progression. Thus, there is an unmet need to develop diagnostic probes for early detection of OC. One approach may rely on RNA as a molecular biomarker. In this regard, FLJ22447 lncRNA is an RNA biomarker that is over-expressed in ovarian cancer (OC) and in cancer-associated fibroblasts (CAFs). CAFs appear early on in OC as they provide a metastatic niche for OC progression. FIT-PNAs (forced intercalation-peptide nucleic acids) are DNA analogs that are designed to fluoresce upon hybridization to their complementary RNA target sequence. In recent studies, we have shown that the introduction of cyclopentane PNAs into FIT-PNAs (cpFIT-PNA) results in superior RNA sensors. Herein, we report the design and synthesis of cpFIT-PNAs for the detection of this RNA biomarker in living OC cells (OVCAR8) and in CAFs. cpFIT-PNA was compared to FIT-PNA and the cell-penetrating peptide (CPP) of choice was either a simple one (four L-lysines) or a CPP with enhanced cellular uptake (CLIP6). The combination of CLIP6 with cpFIT-PNA resulted in a superior sensing of FLJ22447 lncRNA in OVCAR8 cells as well as in CAFs. Moreover, incubation of CLIP6-cpFIT-PNA in OVCAR8 cells leads to a significant decrease (ca. 60%) in FLJ22447 lncRNA levels and in cell viability, highlighting the potential theranostic use of such molecules.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Ácidos Nucleicos de Péptidos / Ciclopentanos / ARN Largo no Codificante Límite: Female / Humans Idioma: En Revista: Biomolecules Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Ácidos Nucleicos de Péptidos / Ciclopentanos / ARN Largo no Codificante Límite: Female / Humans Idioma: En Revista: Biomolecules Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Suiza