PMID- 34299186
OWN - NLM
STAT- MEDLINE
DCOM- 20210819
LR  - 20210819
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 14
DP  - 2021 Jul 15
TI  - Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic 
      Cells: Role of PI3K/AKT Pathway.
LID - 10.3390/ijms22147564 [doi]
LID - 7564
AB  - Hypoxia is a key component of the tumor microenvironment (TME) and promotes not 
      only tumor growth and metastasis, but also negatively affects infiltrating immune 
      cells by impairing host immunity. Dendritic cells (DCs) are the most potent 
      antigen-presenting cells and their biology is weakened in the TME in many ways, 
      including the modulation of their viability. RNASET2 belongs to the T2 family of 
      extracellular ribonucleases and, besides its nuclease activity, it exerts many 
      additional functions. Indeed, RNASET2 is involved in several human pathologies, 
      including cancer, and it is functionally relevant in the TME. RNASET2 functions 
      are not restricted to cancer cells and its expression could be relevant also in 
      other cell types which are important players in the TME, including DCs. 
      Therefore, this study aimed to unravel the effect of hypoxia (2% O(2)) on the 
      expression of RNASET2 in DCs. Here, we showed that hypoxia enhanced the 
      expression and secretion of RNASET2 in human monocyte-derived DCs. This 
      paralleled the HIF-1alpha accumulation and HIF-dependent and -independent signaling, 
      which are associated with DCs' survival/autophagy/apoptosis. RNASET2 expression, 
      under hypoxia, was regulated by the PI3K/AKT pathway and was almost completely 
      abolished by TLR4 ligand, LPS. Taken together, these results highlight how 
      hypoxia- dependent and -independent pathways shape RNASET2 expression in DCs, 
      with new perspectives on its implication for TME and, therefore, in anti-tumor 
      immunity.
FAU - Monaci, Sara
AU  - Monaci S
AUID- ORCID: 0000-0002-7631-284X
AD  - Cellular and Molecular Physiology Unit, Department of Molecular and Developmental 
      Medicine, University of Siena, 53100 Siena, Italy.
FAU - Coppola, Federica
AU  - Coppola F
AUID- ORCID: 0000-0002-7201-5741
AD  - Cellular and Molecular Physiology Unit, Department of Molecular and Developmental 
      Medicine, University of Siena, 53100 Siena, Italy.
FAU - Giuntini, Gaia
AU  - Giuntini G
AUID- ORCID: 0000-0001-6643-1354
AD  - Cellular and Molecular Physiology Unit, Department of Molecular and Developmental 
      Medicine, University of Siena, 53100 Siena, Italy.
FAU - Roncoroni, Rossella
AU  - Roncoroni R
AD  - Department of Biotechnologies and Life Sciences, University of Insubria, 21100 
      Varese, Italy.
FAU - Acquati, Francesco
AU  - Acquati F
AUID- ORCID: 0000-0002-9537-400X
AD  - Department of Biotechnologies and Life Sciences, University of Insubria, 21100 
      Varese, Italy.
FAU - Sozzani, Silvano
AU  - Sozzani S
AUID- ORCID: 0000-0002-3144-8743
AD  - Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 
      Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy.
AD  - IRCCS Neuromed, 86077 Pozzilli, Italy.
FAU - Carraro, Fabio
AU  - Carraro F
AUID- ORCID: 0000-0003-0771-042X
AD  - Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
FAU - Naldini, Antonella
AU  - Naldini A
AUID- ORCID: 0000-0002-9600-2486
AD  - Cellular and Molecular Physiology Unit, Department of Molecular and Developmental 
      Medicine, University of Siena, 53100 Siena, Italy.
LA  - eng
GR  - PRIN 2017NTK4HY/Ministero dell'Istruzione, dell'Universita e della Ricerca/
GR  - PRIN 20177J4E75/Ministero dell'Istruzione, dell'Universita e della Ricerca/
GR  - IG 2017 - ID. 20776/Associazione Italiana per la Ricerca sul Cancro/
PT  - Journal Article
DEP - 20210715
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.- (Ribonucleases)
RN  - EC 3.1.27.- (RNASET2 protein, human)
SB  - IM
MH  - Apoptosis/physiology
MH  - Autophagy/physiology
MH  - Cell Hypoxia/*physiology
MH  - Cells, Cultured
MH  - Dendritic Cells/immunology/*metabolism/pathology
MH  - Humans
MH  - Monocytes/immunology/*metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Ribonucleases/biosynthesis/immunology/*metabolism
MH  - Signal Transduction
MH  - Tumor Suppressor Proteins/biosynthesis/immunology/*metabolism
PMC - PMC8303897
OTO - NOTNLM
OT  - RNASET2
OT  - dendritic cell
OT  - hypoxia
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/25 06:00
MHDA- 2021/08/20 06:00
PMCR- 2021/07/15
CRDT- 2021/07/24 01:02
PHST- 2021/06/24 00:00 [received]
PHST- 2021/07/08 00:00 [revised]
PHST- 2021/07/11 00:00 [accepted]
PHST- 2021/07/24 01:02 [entrez]
PHST- 2021/07/25 06:00 [pubmed]
PHST- 2021/08/20 06:00 [medline]
PHST- 2021/07/15 00:00 [pmc-release]
AID - ijms22147564 [pii]
AID - ijms-22-07564 [pii]
AID - 10.3390/ijms22147564 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jul 15;22(14):7564. doi: 10.3390/ijms22147564.