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Conference Paper: Depleting upregulated DNA polymerase theta (pol θ) in esophageal squamous cell carcinoma (ESCC) inhibits tumor growth, promotes genome instability, and induces ISGs expression through cGAS activation

TitleDepleting upregulated DNA polymerase theta (pol θ) in esophageal squamous cell carcinoma (ESCC) inhibits tumor growth, promotes genome instability, and induces ISGs expression through cGAS activation
Authors
KeywordsPOLQ
genomic instability
innate immune response
Issue Date2021
Citation
The 1st International Electronic Conference on Cancers (IECC): Exploiting Cancer Vulnerability by Targeting the DNA Damage Response, Virtual Meeting,1-14 February 2021 How to Cite?
AbstractOverexpression of the specialized DNA polymerase theta (POLQ) is frequent in breast, colon and lung cancers and has been correlated with unfavorable clinical outcomes. Here, we aimed to determine the importance and functional role of POLQ in esophageal squamous cell carcinoma (ESCC). Integrated analysis of four RNA-seq datasets showed POLQ was predominantly upregulated in ESCC tumors. High expression of POLQ was also observed in a cohort of 25 Hong Kong ESCC patients and negatively correlated with ESCC patient survival. POLQ knockout (KO) ESCC cells were sensitized to multiple genotoxic agents. Both rH2AX foci staining and the comet assay indicated a higher level of genomic instability in POLQ-depleted cells. Double KO of POLQ and FANCD2, known to promote POLQ recruitment at sites of damage, significantly impaired cell proliferation both in vitro and in vivo, as compared to either single POLQ or FANCD2 KOs. A significantly increased number of micronuclei was observed in POLQ and/or FANCD2 KO ESCC cells. Loss of POLQ and/or FANCD2 also resulted in the activation of cGAS and upregulation of interferon-stimulated genes (ISGs). Our results suggest that high abundance of POLQ in ESCC contributes to the malignant phenotype through genome instability and activation of the cGAS pathway.
DescriptionSession 6: Targeting with immune checkpoint inhibitors
Persistent Identifierhttp://hdl.handle.net/10722/301448

 

DC FieldValueLanguage
dc.contributor.authorLi, J-
dc.contributor.authorKo, JMY-
dc.contributor.authorDai, W-
dc.contributor.authorNg, HY-
dc.contributor.authorYu, Z-
dc.contributor.authorBergoglio, V-
dc.contributor.authorHoffmann, JS-
dc.contributor.authorLung, ML-
dc.date.accessioned2021-07-27T08:11:14Z-
dc.date.available2021-07-27T08:11:14Z-
dc.date.issued2021-
dc.identifier.citationThe 1st International Electronic Conference on Cancers (IECC): Exploiting Cancer Vulnerability by Targeting the DNA Damage Response, Virtual Meeting,1-14 February 2021-
dc.identifier.urihttp://hdl.handle.net/10722/301448-
dc.descriptionSession 6: Targeting with immune checkpoint inhibitors-
dc.description.abstractOverexpression of the specialized DNA polymerase theta (POLQ) is frequent in breast, colon and lung cancers and has been correlated with unfavorable clinical outcomes. Here, we aimed to determine the importance and functional role of POLQ in esophageal squamous cell carcinoma (ESCC). Integrated analysis of four RNA-seq datasets showed POLQ was predominantly upregulated in ESCC tumors. High expression of POLQ was also observed in a cohort of 25 Hong Kong ESCC patients and negatively correlated with ESCC patient survival. POLQ knockout (KO) ESCC cells were sensitized to multiple genotoxic agents. Both rH2AX foci staining and the comet assay indicated a higher level of genomic instability in POLQ-depleted cells. Double KO of POLQ and FANCD2, known to promote POLQ recruitment at sites of damage, significantly impaired cell proliferation both in vitro and in vivo, as compared to either single POLQ or FANCD2 KOs. A significantly increased number of micronuclei was observed in POLQ and/or FANCD2 KO ESCC cells. Loss of POLQ and/or FANCD2 also resulted in the activation of cGAS and upregulation of interferon-stimulated genes (ISGs). Our results suggest that high abundance of POLQ in ESCC contributes to the malignant phenotype through genome instability and activation of the cGAS pathway.-
dc.languageeng-
dc.relation.ispartofThe 1st International Electronic Conference on Cancers (IECC): Exploiting Cancer Vulnerability by Targeting the DNA Damage Response-
dc.subjectPOLQ-
dc.subjectgenomic instability-
dc.subjectinnate immune response-
dc.titleDepleting upregulated DNA polymerase theta (pol θ) in esophageal squamous cell carcinoma (ESCC) inhibits tumor growth, promotes genome instability, and induces ISGs expression through cGAS activation-
dc.typeConference_Paper-
dc.identifier.emailKo, JMY: joko@hku.hk-
dc.identifier.emailDai, W: weidai2@hku.hk-
dc.identifier.emailNg, HY: hyng0812@hku.hk-
dc.identifier.emailYu, Z: zvyu@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityKo, JMY=rp02011-
dc.identifier.authorityDai, W=rp02146-
dc.identifier.authorityYu, Z=rp02756-
dc.identifier.authorityLung, ML=rp00300-
dc.identifier.hkuros323423-

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