File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: PIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma

TitlePIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma
Authors
Issue Date2021
PublisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/sigtrans/
Citation
Signal Transduction and Targeted Therapy, 2021, v. 6 n. 1, p. article no. 86 How to Cite?
AbstractAltered energy metabolism of cancer cells shapes the immune cell response in the tumor microenvironment that facilitates tumor progression. Herein, we reported the novel of tumor cell-expressed Piwi Like RNA-Mediated Gene Silencing 1 (PIWIL1) in mediating the crosstalk of fatty acid metabolism and immune response of human hepatocellular carcinoma (HCC). PIWIL1 expression in HCC was increased compared to normal hepatic tissues and was positively correlated with the proliferation rate of HCC cell lines. PIWIL1 overexpression accelerated in vitro proliferation and in vivo growth of HCC tumors, while PIWIL1 knockdown showed opposite effects. PIWIL1 increased oxygen consumption and energy production via fatty acid metabolism without altering aerobic glycolysis. Inhibition of fatty acid metabolism abolished PIWIL1-induced HCC proliferation and growth. RNA-seq analysis revealed that immune system regulation might be involved, which was echoed by the experimental observation that PIWIL1-overexpressing HCC cells attracted myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment. MDSCs depletion reduced the proliferation and growth of PIWIL1-overexpressing HCC tumors. Complement C3, whose secretion was induced by PIWIL1 in HCC cells, mediates the interaction of HCC cells with MDSCs by activated p38 MAPK signaling in MDSCs, which in turn initiated expression of immunosuppressive cytokine IL10. Neutralizing IL10 secretion reduced the immunosuppressive activity of MDSCs in the microenvironment of PIWIL1-overexpressing HCC. Taken together, our study unraveled the critical role of PIWIL1 in initiating the interaction of cancer cell metabolism and immune cell response in HCC. Tumor cells-expressed PIWIL1 may be a potential target for the development of novel HCC treatment.
Persistent Identifierhttp://hdl.handle.net/10722/297610
ISSN
2023 Impact Factor: 40.8
2023 SCImago Journal Rankings: 8.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, N-
dc.contributor.authorTan, HY-
dc.contributor.authorLu, Y-
dc.contributor.authorChan, YT-
dc.contributor.authorWang, D-
dc.contributor.authorGuo, W-
dc.contributor.authorXu, Y-
dc.contributor.authorZhang, C-
dc.contributor.authorChen, F-
dc.contributor.authorTang, G-
dc.contributor.authorFeng, Y-
dc.date.accessioned2021-03-23T04:19:24Z-
dc.date.available2021-03-23T04:19:24Z-
dc.date.issued2021-
dc.identifier.citationSignal Transduction and Targeted Therapy, 2021, v. 6 n. 1, p. article no. 86-
dc.identifier.issn2059-3635-
dc.identifier.urihttp://hdl.handle.net/10722/297610-
dc.description.abstractAltered energy metabolism of cancer cells shapes the immune cell response in the tumor microenvironment that facilitates tumor progression. Herein, we reported the novel of tumor cell-expressed Piwi Like RNA-Mediated Gene Silencing 1 (PIWIL1) in mediating the crosstalk of fatty acid metabolism and immune response of human hepatocellular carcinoma (HCC). PIWIL1 expression in HCC was increased compared to normal hepatic tissues and was positively correlated with the proliferation rate of HCC cell lines. PIWIL1 overexpression accelerated in vitro proliferation and in vivo growth of HCC tumors, while PIWIL1 knockdown showed opposite effects. PIWIL1 increased oxygen consumption and energy production via fatty acid metabolism without altering aerobic glycolysis. Inhibition of fatty acid metabolism abolished PIWIL1-induced HCC proliferation and growth. RNA-seq analysis revealed that immune system regulation might be involved, which was echoed by the experimental observation that PIWIL1-overexpressing HCC cells attracted myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment. MDSCs depletion reduced the proliferation and growth of PIWIL1-overexpressing HCC tumors. Complement C3, whose secretion was induced by PIWIL1 in HCC cells, mediates the interaction of HCC cells with MDSCs by activated p38 MAPK signaling in MDSCs, which in turn initiated expression of immunosuppressive cytokine IL10. Neutralizing IL10 secretion reduced the immunosuppressive activity of MDSCs in the microenvironment of PIWIL1-overexpressing HCC. Taken together, our study unraveled the critical role of PIWIL1 in initiating the interaction of cancer cell metabolism and immune cell response in HCC. Tumor cells-expressed PIWIL1 may be a potential target for the development of novel HCC treatment.-
dc.languageeng-
dc.publisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/sigtrans/-
dc.relation.ispartofSignal Transduction and Targeted Therapy-
dc.rightsSignal Transduction and Targeted Therapy. Copyright © Nature Research: Fully open access journals.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titlePIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma-
dc.typeArticle-
dc.identifier.emailWang, N: ckwang@hku.hk-
dc.identifier.emailTan, HY: hyhtan@HKUCC-COM.hku.hk-
dc.identifier.emailXu, Y: xyzjh@hku.hk-
dc.identifier.emailFeng, Y: yfeng@hku.hk-
dc.identifier.authorityWang, N=rp02075-
dc.identifier.authorityFeng, Y=rp00466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41392-021-00485-8-
dc.identifier.pmid33633112-
dc.identifier.pmcidPMC7907082-
dc.identifier.scopuseid_2-s2.0-85101764930-
dc.identifier.hkuros321787-
dc.identifier.volume6-
dc.identifier.issue1-
dc.identifier.spagearticle no. 86-
dc.identifier.epagearticle no. 86-
dc.identifier.isiWOS:000624534500001-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats