Scholarlink

Objective <p>Histone lactylation (Hla) represents a novel epigenetic mark priming cells toward the malignant state. Discoidin, CUB, and LCCL domain-containing type I (DCBLD1) has been reported as a carcinogenic gene so far. This project was focused on the functional role of DCBLD1 in oesophageal cancer through the lactate modification pathway. </p> Methods <p>Biological information evaluated DCBLD1, protein disulfide isomerase family A member 3 (PDIA3) expression and the relationship between the two in oesophageal cancer. RT-qPCR and Western blotting were used to detect DCBLD1 and PDIA3 expression. Western blotting also quantified DCBLD1-lysine lactylation (kla) levels. DCBLD1 half-life was checked by chlorhexidine (CHX) assay. EDU, wound healing, transwell, flow cytometry and Seahorse assays individually appraised cell proliferation, migration, apoptosis and glycolysis. Co-IP assay identified DCBLD1-PDIA3 interaction. Xenografted tumorigenesis was estimated, prior to histological assessment by H&amp;E staining. Glucose consumption and lactate production were also examined to detect glycolysis.</p> Results <p>DCBLD1 was highly expressed in esophageal cancer specimens and cells. DCBLD1 half-life was respectively shortened or prolonged in tumor cells challenged with lactate (LA) or the aerobic glycolysis inhibitor 2-deoxy-d-glucose (2-DG). DCBLD1-Kla levels were up-regulated in oesophageal cancer tissues. Lactate dehydrogenase A (LDHA) interference decreased both DCBLD1 expression and DCBLD1-Kla expression. PDIA3 was highly expressed in oesophageal cancer. DCBLD1 was positively correlated with, and interacted with PDIA3 upon LA stimulation. DCBLD1 knockdown inhibited cell proliferation, migration, glycolysis and induced apoptosis, repressed tumor progress and glycolysis in vivo, which were all partially recovered by PDIA3 overexpression. Further LDHA down-regulation aggravated the impacts of DCBLD1 knockdown and PDIA3 overexpression both in vitro and in vivo.</p> Conclusion <p>It was established that DCBLD1 lactylation bound to PDIA3, contributing to oesophageal cancer malignancy and glycolysis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Lactylation-augmented DCBLD1-mediated PDIA3 stabilization reprograms glycolysis metabolism in oesophageal cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月31日

查看全文
  • Ming Yin,
  • Shan Wang,
  • HaiMin Liu,
  • Chaochen Xu,
  • Qiushuo Li,
  • YunHao Sun

摘要

Objective

Histone lactylation (Hla) represents a novel epigenetic mark priming cells toward the malignant state. Discoidin, CUB, and LCCL domain-containing type I (DCBLD1) has been reported as a carcinogenic gene so far. This project was focused on the functional role of DCBLD1 in oesophageal cancer through the lactate modification pathway.

Methods

Biological information evaluated DCBLD1, protein disulfide isomerase family A member 3 (PDIA3) expression and the relationship between the two in oesophageal cancer. RT-qPCR and Western blotting were used to detect DCBLD1 and PDIA3 expression. Western blotting also quantified DCBLD1-lysine lactylation (kla) levels. DCBLD1 half-life was checked by chlorhexidine (CHX) assay. EDU, wound healing, transwell, flow cytometry and Seahorse assays individually appraised cell proliferation, migration, apoptosis and glycolysis. Co-IP assay identified DCBLD1-PDIA3 interaction. Xenografted tumorigenesis was estimated, prior to histological assessment by H&E staining. Glucose consumption and lactate production were also examined to detect glycolysis.

Results

DCBLD1 was highly expressed in esophageal cancer specimens and cells. DCBLD1 half-life was respectively shortened or prolonged in tumor cells challenged with lactate (LA) or the aerobic glycolysis inhibitor 2-deoxy-d-glucose (2-DG). DCBLD1-Kla levels were up-regulated in oesophageal cancer tissues. Lactate dehydrogenase A (LDHA) interference decreased both DCBLD1 expression and DCBLD1-Kla expression. PDIA3 was highly expressed in oesophageal cancer. DCBLD1 was positively correlated with, and interacted with PDIA3 upon LA stimulation. DCBLD1 knockdown inhibited cell proliferation, migration, glycolysis and induced apoptosis, repressed tumor progress and glycolysis in vivo, which were all partially recovered by PDIA3 overexpression. Further LDHA down-regulation aggravated the impacts of DCBLD1 knockdown and PDIA3 overexpression both in vitro and in vivo.

Conclusion

It was established that DCBLD1 lactylation bound to PDIA3, contributing to oesophageal cancer malignancy and glycolysis.