Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway
BackgroundPancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is a highly lethal malignancy with poor prognosis. Polypeptide N-acetylgalactosaminyltransferase-6 (GALNT6) is frequently overexpressed in PDAC. However, the role of GALNT6 in the PDAC remains unclear.Me...
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| Format: | Article |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1097772/full |
| _version_ | 1811163387054260224 |
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| author | Mengyang Ding Mengyang Ding Mengyang Ding Jingyu Liu Jingyu Liu Jingyu Liu Honghui Lv Honghui Lv Honghui Lv Yanlin Zhu Yanlin Zhu Yanlin Zhu Yumiao Chen Yumiao Chen Yumiao Chen Hui Peng Hui Peng Hui Peng Sairong Fan Sairong Fan Sairong Fan Xiaoming Chen Xiaoming Chen Xiaoming Chen |
| author_facet | Mengyang Ding Mengyang Ding Mengyang Ding Jingyu Liu Jingyu Liu Jingyu Liu Honghui Lv Honghui Lv Honghui Lv Yanlin Zhu Yanlin Zhu Yanlin Zhu Yumiao Chen Yumiao Chen Yumiao Chen Hui Peng Hui Peng Hui Peng Sairong Fan Sairong Fan Sairong Fan Xiaoming Chen Xiaoming Chen Xiaoming Chen |
| author_sort | Mengyang Ding |
| collection | DOAJ |
| description | BackgroundPancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is a highly lethal malignancy with poor prognosis. Polypeptide N-acetylgalactosaminyltransferase-6 (GALNT6) is frequently overexpressed in PDAC. However, the role of GALNT6 in the PDAC remains unclear.MethodsThe expression of GALNT6 in pancreatic cancer and normal tissues were analyzed by bioinformatic analyses and immunohistochemistry. CCK8 and colony formation were used to detect cell proliferation. Flow cytometry was applied to detect cell cycle.The pyroptosis was detected by scanning electron microscopy. The mRNA expression was detected by qRT-PCR. The protein expression and localization were detected by western blot and immunofluorescence assay. ELISA was used to detect the levels of inflammatory factors.ResultsThe expression of GALNT6 was associated with advanced tumor stage, and had an area under curve (AUC) value of 0.919 in pancreatic cancer based on the cancer genome atlas (TCGA) dataset. Knockdown of GALNT6 inhibited cell proliferation, migration, invasion and cell cycle arrest of PDAC cells. Meanwhile, knockdown of GALNT6 increased the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18), the release of inflammasome and an increasing of Gasdermin D (GSDMD), N-terminal of GSDMD (GSDMD-N), Gasdermin E (GSDME) and N-terminal of GSDME (GSDME-N) in PDAC cells. GALNT6 suppressed the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and GSDMD by glycosylation of NF-κB and inhibiting the nucleus localization of NF-κB. Additionally, GALNT6 promotes the degradation of GSDME by O-glycosylation.ConclusionWe found that GALNT6 is highly expressed in pancreatic cancer and plays a carcinogenic role. The results suggested that GALNT6 regulates the pyroptosis of PDAC cells through NF-κB/NLRP3/GSDMD and GSDME signaling. Our study might provides novel insights into the roles of GALNT6 in PDAC progression. |
| first_indexed | 2024-04-10T06:44:19Z |
| format | Article |
| id | doaj.art-b285c79f84ee4cef8438538fdf571cd7 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T06:44:19Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-b285c79f84ee4cef8438538fdf571cd72023-02-28T15:12:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-02-011310.3389/fonc.2023.10977721097772Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathwayMengyang Ding0Mengyang Ding1Mengyang Ding2Jingyu Liu3Jingyu Liu4Jingyu Liu5Honghui Lv6Honghui Lv7Honghui Lv8Yanlin Zhu9Yanlin Zhu10Yanlin Zhu11Yumiao Chen12Yumiao Chen13Yumiao Chen14Hui Peng15Hui Peng16Hui Peng17Sairong Fan18Sairong Fan19Sairong Fan20Xiaoming Chen21Xiaoming Chen22Xiaoming Chen23Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaInstitute of Glycobiological Engineering, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaInstitute of Glycobiological Engineering, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaInstitute of Glycobiological Engineering, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaInstitute of Glycobiological Engineering, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaInstitute of Glycobiological Engineering, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaInstitute of Glycobiological Engineering, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaInstitute of Glycobiological Engineering, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaInstitute of Glycobiological Engineering, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaBackgroundPancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is a highly lethal malignancy with poor prognosis. Polypeptide N-acetylgalactosaminyltransferase-6 (GALNT6) is frequently overexpressed in PDAC. However, the role of GALNT6 in the PDAC remains unclear.MethodsThe expression of GALNT6 in pancreatic cancer and normal tissues were analyzed by bioinformatic analyses and immunohistochemistry. CCK8 and colony formation were used to detect cell proliferation. Flow cytometry was applied to detect cell cycle.The pyroptosis was detected by scanning electron microscopy. The mRNA expression was detected by qRT-PCR. The protein expression and localization were detected by western blot and immunofluorescence assay. ELISA was used to detect the levels of inflammatory factors.ResultsThe expression of GALNT6 was associated with advanced tumor stage, and had an area under curve (AUC) value of 0.919 in pancreatic cancer based on the cancer genome atlas (TCGA) dataset. Knockdown of GALNT6 inhibited cell proliferation, migration, invasion and cell cycle arrest of PDAC cells. Meanwhile, knockdown of GALNT6 increased the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18), the release of inflammasome and an increasing of Gasdermin D (GSDMD), N-terminal of GSDMD (GSDMD-N), Gasdermin E (GSDME) and N-terminal of GSDME (GSDME-N) in PDAC cells. GALNT6 suppressed the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and GSDMD by glycosylation of NF-κB and inhibiting the nucleus localization of NF-κB. Additionally, GALNT6 promotes the degradation of GSDME by O-glycosylation.ConclusionWe found that GALNT6 is highly expressed in pancreatic cancer and plays a carcinogenic role. The results suggested that GALNT6 regulates the pyroptosis of PDAC cells through NF-κB/NLRP3/GSDMD and GSDME signaling. Our study might provides novel insights into the roles of GALNT6 in PDAC progression.https://www.frontiersin.org/articles/10.3389/fonc.2023.1097772/fullpancreatic ductal adenocarcinomaGALNT6pyroptosisNF-κBGSDME |
| spellingShingle | Mengyang Ding Mengyang Ding Mengyang Ding Jingyu Liu Jingyu Liu Jingyu Liu Honghui Lv Honghui Lv Honghui Lv Yanlin Zhu Yanlin Zhu Yanlin Zhu Yumiao Chen Yumiao Chen Yumiao Chen Hui Peng Hui Peng Hui Peng Sairong Fan Sairong Fan Sairong Fan Xiaoming Chen Xiaoming Chen Xiaoming Chen Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway Frontiers in Oncology pancreatic ductal adenocarcinoma GALNT6 pyroptosis NF-κB GSDME |
| title | Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway |
| title_full | Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway |
| title_fullStr | Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway |
| title_full_unstemmed | Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway |
| title_short | Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway |
| title_sort | knocking down galnt6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through nf κb nlrp3 gsdmd and gsdme signaling pathway |
| topic | pancreatic ductal adenocarcinoma GALNT6 pyroptosis NF-κB GSDME |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1097772/full |
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