Publications by authors named "Jialei Zhai"

3 Publications

  • Page 1 of 1

MiR-374b-5p inhibits KDM5B-induced epithelial-mesenchymal transition in pancreatic cancer.

Am J Cancer Res 2021 15;11(8):3907-3920. Epub 2021 Aug 15.

Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Affiliated to Capital Medical University Beijing, China.

Micro(mi)RNAs play a critical regulatory role in the progression and metastasis of pancreatic cancer (PC). In this study, we aimed to reveal the mechanisms of miR-374b-5p in regulating epithelial-mesenchymal transition (EMT) in PC. Gene Expression Omnibus datasets (GSE24279 and GSE71533) and the pancreatic ductal adenocarcinoma (PDAC) cohort of The Cancer Genome Atlas were employed to screen for potential prognostic miRNAs. The expression of miR-374b-5p was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in 78 paired PDAC tissue samples. The biological effects of miR-374b-5p were investigated using and assays. Luciferase reporter assays and immunohistochemical tests were conducted to verify the interaction between miR-374b-5p and its predicted direct target, KDM5B. MiR-374b-5p was downregulated in PC tissues, and a low level of miR-374b-5p was associated with poor overall survival, greater tumor size, and more lymph node metastasis in PC. assays indicated that overexpression of miR-374b-5p suppressed the proliferation, migration, and invasion of PC cells. Mechanistically, miR-374b-5p suppressed the expression of KDM5B, which inhibited E-cadherin expression but promoted N-cadherin and vimentin expression. Finally, assays demonstrated that miR-374b-5p overexpression suppressed tumor growth and lung metastasis in PANC-1 cells. Thus, our findings indicate that miR-374b-5p could be a potential prognostic biomarker and therapeutic target for KDM5B-induced EMT in PC.
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August 2021

Single-cell transcriptomics reveals heterogeneous progression and EGFR activation in pancreatic adenosquamous carcinoma.

Int J Biol Sci 2021 22;17(10):2590-2605. Epub 2021 Jun 22.

Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing 100020, China.

Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.
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June 2021

Triptolide inhibits pancreatic cancer cell proliferation and migration via down-regulating PLAU based on network pharmacology of Tripterygium wilfordii Hook F.

Eur J Pharmacol 2020 Aug 25;880:173225. Epub 2020 May 25.

Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China.

Tripterygium wilfordii Hook F (TwHF) exhibits anti-tumor efficacy in pancreatic ductal adenocarcinoma (PDAC), however the pharmacological mechanisms are unclear due to complicated formulae and target genes. Using Traditional Chinese Medicine Systems Pharmacology and GeneCards databases, we performed a network pharmacology (NP) of TwHF and screened out 22 ingredients and 25 target genes associated with PDAC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the 25 target genes were performed. Using STRING database, protein-protein interaction network of the 25 target genes was constructed, and indicated that triptolide (TL)-plasminogen activator urokinase (PLAU) as a potential target for PDAC treatment. Hence, in vitro experiments were performed and validated that TL inhibited PDAC cell proliferation and migration by suppressing PLAU expression. The results of Western blot suggested that PLAU activated endothelial-mesenchymal transition (EMT) progression. In two Gene Expression Omnibus datasets (GSE16515 and GSE28735), PLAU was up-regulated in tumor tissues, and PLAU overexpression was associated with poor overall survival of PDAC cohort of The Cancer Genome Atlas (P < 0.01). Immunohistochemistry illustrated that overexpression of PLAU protein was related to lymph node metastasis in 20 PDAC patients (P < 0.01). Based on NP of TwHF, we identified and validated that TL-PLAU could serve as a potential target for PDAC treatment.
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August 2020