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The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer.

ABSTRACT: Aberrant expression of the glycoprotein mucin-1 (MUC1) has been associated with pancreatic cancer progression and metastasis as a result of mediating the oncogenic transcriptional regulation of target genes. In the present study, we demonstrate that MUC1 downregulates the expression of the tumor suppressor polypeptide N-acetylgalactosaminyltransferase 5 in pancreatic cancer. ChIP-on-chip analysis revealed that the MUC1 cytoplasmic tail binds to regulatory elements in the GALNT5 gene. Additionally, MUC1 increases binding of p53 and c-Jun and decreases the binding of Sp1 to the proximal promoter and exonic regions of GALNT5. We also observed that expression of N-acetylgalactosaminyltransferase 5 is inversionally proportional to MUC1 expression in human pancreatic cancer. These results demonstrate that MUC1 downregulates the expression of N-acetylgalactosaminyltransferase 5 in pancreatic cancer by modifying the promoter occupancy of transcription factors through its cytoplasmic domain.

SUBMITTER: Caffrey T

PROVIDER: S-EPMC7048170 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer.

Caffrey Thomas T Sagar Satish S Thomas Divya D Lewallen Michelle E ME Hollingsworth Michael A MA Radhakrishnan Prakash P

FEBS letters 20190721 19

Aberrant expression of the glycoprotein mucin-1 (MUC1) has been associated with pancreatic cancer progression and metastasis as a result of mediating the oncogenic transcriptional regulation of target genes. In the present study, we demonstrate that MUC1 downregulates the expression of the tumor suppressor polypeptide N-acetylgalactosaminyltransferase 5 in pancreatic cancer. ChIP-on-chip analysis revealed that the MUC1 cytoplasmic tail binds to regulatory elements in the GALNT5 gene. Additionall ...[more]

PMID: 31283009

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Project description:Purpose:STARD13 is regulated by various miRNAs. However, there are relatively few reports describing the relationship between miRNAs and STARD13 in pancreatic cancer. Therefore, the aim of this study was to explore the relationship between miRNA and STARD13 in pancreatic cancer. Patients and Methods:By analyzing the data from Gene Expression Omnibus (GEO) database, the relationship between STARD13 expression and pancreatic cancer was explored. Then, through sequence alignment, the sequence complementary to miR-887-3p in the 3'UTR of STARD13 mRNA was found, mutated and cloned. Dual-luciferase reporter assay was used to test the relationship between STARD13 and miR-887-3p. Pancreatic cancer tumor tissue and its adjacent tissues collected, and the expression of STARD13 and miR-887-3p in pancreatic cancer tissues was analyzed by RT-qPCR. After, miR-887-3p and its inhibitor were transfected into PANC-1 cells to further confirm the regulatory relationship between miR-887-3 and STARD13 by RT-qPCR, and CCK-8, colony formation assays, cell cycle analysis, apoptosis detection and transwell analysis were used to detect changes of proliferation, apoptosis, migration and invasion in PANC-1 cells. Finally, through in vivo experiments, the effect of miR-887-3p on tumor growth was researched. Results:We found that STARD13 expression is lower in pancreatic cancer tissues, with the level of miR-887-3p being higher in these tissues. Pancreatic cancer patients with particularly low levels of STARD13 presented with a poor prognosis. MiR-887-3p negatively regulates the expression of STARD13. Increasing levels of miR-887-3p decreased the expression of STARD13, which promoted the proliferation, cell cycle process, cell migration and invasion, and inhibited the apoptosis of pancreatic cancer cells. Inhibition of miR-887-3p in SCID mice could inhibit tumor growth and promote tumor cell apoptosis. Conclusion:In conclusion, STARD13 is negatively regulated by miR-887-3p in pancreatic cancer. MiR-877-3p may act to promote cancer progression, and as such, it is a viable target for intervention and diagnostic development.

Dataset Information

The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer.

Publications

The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer.

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