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Effect of Polypurine Reverse Hoogsteen Hairpins on Relevant Cancer Target Genes in Different Human Cell Lines.
Villalobos, Xenia; Rodríguez, Laura; Solé, Anna; Lliberós, Carolina; Mencia, Núria; Ciudad, Carlos J; Noé, Véronique.
Affiliation
  • Villalobos X; Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona , Barcelona, Spain .
  • Rodríguez L; Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona , Barcelona, Spain .
  • Solé A; Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona , Barcelona, Spain .
  • Lliberós C; Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona , Barcelona, Spain .
  • Mencia N; Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona , Barcelona, Spain .
  • Ciudad CJ; Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona , Barcelona, Spain .
  • Noé V; Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona , Barcelona, Spain .
Nucleic Acid Ther ; 25(4): 198-208, 2015 Aug.
Article in En | MEDLINE | ID: mdl-26042602
We studied the ability of polypurine reverse Hoogsteen hairpins (PPRHs) to silence a variety of relevant cancer-related genes in several human cell lines. PPRHs are hairpins formed by two antiparallel polypurine strands bound by intramolecular Hoogsteen bonds linked by a pentathymidine loop. These hairpins are able to bind to their target DNA sequence through Watson-Crick bonds producing specific silencing of gene expression. We designed PPRHs against the following genes: BCL2, TOP1, mTOR, MDM2, and MYC and tested them for mRNA levels, cytotoxicity, and apoptosis in prostate, pancreas, colon, and breast cancer cell lines. Even though all PPRHs were effective, the most remarkable results were obtained with those against BCL2 and mammalian target of rapamycin (mTOR) in decreasing cell survival and mRNA levels and increasing apoptosis in prostate, colon, and pancreatic cancer cells. In the case of TOP1, MDM2, and MYC, their corresponding PPRHs produced a strong effect in decreasing cell viability and mRNA levels and increasing apoptosis in breast cancer cells. Thus, we confirm that the PPRH technology is broadly useful to silence the expression of cancer-related genes as demonstrated using target genes involved in metabolism (DHFR), proliferation (mTOR), DNA topology (TOP1), lifespan and senescence (telomerase), apoptosis (survivin, BCL2), transcription factors (MYC), and proto-oncogenes (MDM2).
Subject(s)
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Collection: 01-internacional Database: MEDLINE Main subject: Poly T / RNA, Messenger / Gene Silencing / Genes, Neoplasm / Inverted Repeat Sequences Limits: Female / Humans / Male Language: En Journal: Nucleic Acid Ther Year: 2015 Document type: Article Affiliation country: Spain Country of publication: United States
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Collection: 01-internacional Database: MEDLINE Main subject: Poly T / RNA, Messenger / Gene Silencing / Genes, Neoplasm / Inverted Repeat Sequences Limits: Female / Humans / Male Language: En Journal: Nucleic Acid Ther Year: 2015 Document type: Article Affiliation country: Spain Country of publication: United States