PMID- 36361992
OWN - NLM
STAT- MEDLINE
DCOM- 20221125
LR  - 20221125
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 21
DP  - 2022 Oct 30
TI  - The BRCT Domain from the Homologue of the Oncogene PES1 in Leishmania major 
      (LmjPES) Promotes Malignancy and Drug Resistance in Mammalian Cells.
LID - 10.3390/ijms232113203 [doi]
LID - 13203
AB  - Around 15% of cancer cases are attributable to infectious agents. Epidemiological 
      studies suggest that an association between leishmaniasis and cancer does exist. 
      Recently, the homologue of PES1 in Leishmania major (LmjPES) was described to be 
      involved in parasite infectivity. Mammalian PES1 protein has been implicated in 
      cellular processes like cell cycle regulation. Its BRCT domain has been 
      identified as a key factor in DNA damage-responsive checkpoints. This work aimed 
      to elucidate the hypothetical oncogenic implication of BRCT domain from LmjPES in 
      host cells. We generated a lentivirus carrying this BRCT domain sequence 
      (lentiBRCT) and a lentivirus expressing the luciferase protein (lentiLuc), as 
      control. Then, HEK293T and NIH/3T3 mammalian cells were infected with these 
      lentiviruses. We observed that the expression of BRCT domain from LmjPES 
      conferred to mammal cells in vitro a greater replication rate and higher 
      survival. In in vivo experiments, we observed faster tumor growth in mice 
      inoculated with lentiBRCT respect to lentiLuc HEK293T infected cells. Moreover, 
      the lentiBRCT infected cells were less sensitive to the genotoxic drugs. 
      Accordingly, gene expression profiling analysis revealed that BRCT domain from 
      LmjPES protein altered the expression of proliferation- (DTX3L, CPA4, BHLHE41, 
      BMP2, DHRS2, S100A1 and PARP9), survival- (BMP2 and CARD9) and 
      chemoresistance-related genes (DPYD, Dok3, DTX3L, PARP9 and DHRS2). Altogether, 
      our results reinforced the idea that in eukaryotes, horizontal gene transfer 
      might be also achieved by parasitism like Leishmania infection driving therefore 
      to some crucial biological changes such as proliferation and drug resistance.
FAU - Larrea, Esther
AU  - Larrea E
AUID- ORCID: 0000-0002-1443-6513
AD  - ISTUN Institute of Tropical Health, IdiSNA (Navarra Institute for Health 
      Research), University of Navarra, 31009 Pamplona, Navarra, Spain.
FAU - Fernandez-Rubio, Celia
AU  - Fernandez-Rubio C
AUID- ORCID: 0000-0001-5254-8121
AD  - ISTUN Institute of Tropical Health, IdiSNA (Navarra Institute for Health 
      Research), University of Navarra, 31009 Pamplona, Navarra, Spain.
AD  - ISTUN Institute of Tropical Health, Department of Microbiology and Parasitology, 
      IdiSNA (Navarra Institute for Health Research), University of Navarra, 31009 
      Pamplona, Navarra, Spain.
FAU - Pena-Guerrero, Jose
AU  - Pena-Guerrero J
AUID- ORCID: 0000-0002-9183-6369
AD  - ISTUN Institute of Tropical Health, IdiSNA (Navarra Institute for Health 
      Research), University of Navarra, 31009 Pamplona, Navarra, Spain.
AD  - ISTUN Institute of Tropical Health, Department of Microbiology and Parasitology, 
      IdiSNA (Navarra Institute for Health Research), University of Navarra, 31009 
      Pamplona, Navarra, Spain.
FAU - Guruceaga, Elizabeth
AU  - Guruceaga E
AUID- ORCID: 0000-0003-0547-681X
AD  - Bioinformatics Platform, Center for Applied Medical Research, IdiSNA (Navarra 
      Institute for Health Research), University of Navarra, 31009 Pamplona, Navarra, 
      Spain.
FAU - Nguewa, Paul A
AU  - Nguewa PA
AUID- ORCID: 0000-0002-2193-7316
AD  - ISTUN Institute of Tropical Health, IdiSNA (Navarra Institute for Health 
      Research), University of Navarra, 31009 Pamplona, Navarra, Spain.
AD  - ISTUN Institute of Tropical Health, Department of Microbiology and Parasitology, 
      IdiSNA (Navarra Institute for Health Research), University of Navarra, 31009 
      Pamplona, Navarra, Spain.
LA  - eng
GR  - PID2020-112713RB-C21/Spanish Ministry of Science and Innovation/
GR  - LCF/PR/PR13/51080005/Fundacion La Caixa/
GR  - 2022/Fundacion Roviralta/
GR  - 2022/Ubesol/
PT  - Journal Article
DEP - 20221030
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CARD Signaling Adaptor Proteins)
RN  - 0 (Card9 protein, mouse)
RN  - EC 1.1.1.184 (DHRS2 protein, human)
RN  - 0 (Dok3 protein, mouse)
RN  - 0 (PES1 protein, human)
RN  - 0 (Proteins)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - CARD Signaling Adaptor Proteins/metabolism
MH  - HEK293 Cells
MH  - *Leishmania major/genetics/metabolism
MH  - Mammals/metabolism
MH  - Oncogenes
MH  - Proteins/metabolism
MH  - *RNA-Binding Proteins/genetics
MH  - Leishmaniasis/complications
MH  - *Drug Resistance, Neoplasm/genetics
MH  - *Carcinogenesis/genetics
PMC - PMC9655562
OTO - NOTNLM
OT  - BRCT domain
OT  - LmjPES1
OT  - cancer
OT  - cell survival
OT  - drug resistance
OT  - gene expression
OT  - leishmaniasis
OT  - oncogene and cellular proliferation
COIS- The authors declare no conflict of interest.
EDAT- 2022/11/12 06:00
MHDA- 2022/11/15 06:00
PMCR- 2022/10/30
CRDT- 2022/11/11 01:26
PHST- 2022/09/23 00:00 [received]
PHST- 2022/10/20 00:00 [revised]
PHST- 2022/10/21 00:00 [accepted]
PHST- 2022/11/11 01:26 [entrez]
PHST- 2022/11/12 06:00 [pubmed]
PHST- 2022/11/15 06:00 [medline]
PHST- 2022/10/30 00:00 [pmc-release]
AID - ijms232113203 [pii]
AID - ijms-23-13203 [pii]
AID - 10.3390/ijms232113203 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Oct 30;23(21):13203. doi: 10.3390/ijms232113203.