PMID- 26042602
OWN - NLM
STAT- MEDLINE
DCOM- 20160415
LR  - 20211203
IS  - 2159-3345 (Electronic)
IS  - 2159-3337 (Linking)
VI  - 25
IP  - 4
DP  - 2015 Aug
TI  - Effect of Polypurine Reverse Hoogsteen Hairpins on Relevant Cancer Target Genes 
      in Different Human Cell Lines.
PG  - 198-208
AB  - 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).
FAU - Villalobos, Xenia
AU  - Villalobos X
AD  - Department of Biochemistry and Molecular Biology, School of Pharmacy, University 
      of Barcelona , Barcelona, Spain .
FAU - Rodriguez, Laura
AU  - Rodriguez L
AD  - Department of Biochemistry and Molecular Biology, School of Pharmacy, University 
      of Barcelona , Barcelona, Spain .
FAU - Sole, Anna
AU  - Sole A
AD  - Department of Biochemistry and Molecular Biology, School of Pharmacy, University 
      of Barcelona , Barcelona, Spain .
FAU - Lliberos, Carolina
AU  - Lliberos C
AD  - Department of Biochemistry and Molecular Biology, School of Pharmacy, University 
      of Barcelona , Barcelona, Spain .
FAU - Mencia, Nuria
AU  - Mencia N
AD  - Department of Biochemistry and Molecular Biology, School of Pharmacy, University 
      of Barcelona , Barcelona, Spain .
FAU - Ciudad, Carlos J
AU  - Ciudad CJ
AD  - Department of Biochemistry and Molecular Biology, School of Pharmacy, University 
      of Barcelona , Barcelona, Spain .
FAU - Noe, Veronique
AU  - Noe V
AD  - Department of Biochemistry and Molecular Biology, School of Pharmacy, University 
      of Barcelona , Barcelona, Spain .
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150604
PL  - United States
TA  - Nucleic Acid Ther
JT  - Nucleic acid therapeutics
JID - 101562758
RN  - 0 (BCL2 protein, human)
RN  - 0 (MYC protein, human)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Messenger)
RN  - 25086-81-1 (Poly T)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 5.99.1.2 (DNA Topoisomerases, Type I)
RN  - EC 5.99.1.2 (TOP1 protein, human)
SB  - IM
MH  - Apoptosis/genetics
MH  - Base Pairing
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - DNA Topoisomerases, Type I/genetics/metabolism
MH  - Female
MH  - *Gene Silencing
MH  - *Genes, Neoplasm
MH  - Humans
MH  - *Inverted Repeat Sequences
MH  - Male
MH  - Poly T/*genetics/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors/genetics/metabolism
MH  - Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors/genetics/metabolism
MH  - Proto-Oncogene Proteins c-myc/antagonists & inhibitors/genetics/metabolism
MH  - RNA, Messenger/*antagonists & inhibitors/genetics/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/genetics/metabolism
EDAT- 2015/06/05 06:00
MHDA- 2016/04/16 06:00
CRDT- 2015/06/05 06:00
PHST- 2015/06/05 06:00 [entrez]
PHST- 2015/06/05 06:00 [pubmed]
PHST- 2016/04/16 06:00 [medline]
AID - 10.1089/nat.2015.0531 [pii]
AID - 10.1089/nat.2015.0531 [doi]
PST - ppublish
SO  - Nucleic Acid Ther. 2015 Aug;25(4):198-208. doi: 10.1089/nat.2015.0531. Epub 2015 
      Jun 4.