Detecting the FLJ22447 lncRNA in Ovarian Cancer with Cyclopentane-Modified FIT-PNAs (cpFIT-PNAs)

Sheethal Thomas Mannully, Rawan Mahajna, Huda Nazzal, Salam Maree, Hongchao Zheng, Daniel H. Appella, Reuven Reich, Eylon Yavin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number609
JournalBiomolecules
Volume14
Issue number6
DOIs
StatePublished - Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

  • cancer-associated fibroblasts
  • cell-penetrating peptide
  • cyclopentane modified FIT-PNA
  • FLJ22447 lncRNA
  • ovarian cancer
  • RNA biomarker

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