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Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. Cell-cycle-related and expression-elevated protein in tumor (CREPT) plays an important role in the phosphorylation of RNA Pol II, and has been implicated in the development of several types of cancer. As yet, however, there have been no reports on its role in PDAC. Here, we aimed to explore the value of CREPT as a prognostic biomarker in PDAC., Methods: CREPT expression was assessed by immunohistochemistry (IHC) on a tissue microarray containing samples from 375 PDAC patients. Kaplan-Meier and Cox regression analyses were performed to explore the independent prognostic value of CREPT expression for the disease-free survival (DFS) and overall survival (OS) of PDAC patients. A Cell Counting Kit-8 (CCK8) assay was used to determine the growth rates and gemcitabine sensitivities of PDAC cells, while a Transwell assay was used to determine the migration and invasion abilities of PDAC cells. Subcutaneous xenografts were used to explore the effect of CREPT expression on tumor growth in vivo., Results: We found that CREPT is highly expressed in tumor tissues and may serve as an independent prognostic biomarker for DFS and OS of PDAC patients. In vitro assays revealed that CREPT expression promotes the proliferation, migration, invasion and gemcitabine resistance of PDAC cells, and in vivo assays showed that CREPT expression knockdown led to inhibition of PDAC tumor growth., Conclusions: We conclude that high CREPT expression enhances the proliferation, migration, invasion and gemcitabine resistance of PDAC cells. In addition, we conclude that CREPT may serve as an independent prognostic biomarker and therapeutic target for PDAC patients.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal malignancy, with an average 5-year survival rate of 9% (Siegel RL, Miller KD, Jemal A. Ca Cancer J Clin. 2019;69(1):7-34). The steady increase in mortality rate indicates limited efficacy of the conventional regimen. The heterogeneity of PDAC calls for personalized treatment in clinical practice, which requires the construction of a preclinical system for generating patient-derived models. Currently, the lack of high-quality preclinical models results in ineffective translation of novel targeted therapeutics. This review summarizes applications of commonly used models, discusses major difficulties in PDAC model construction and provides recommendations for integrating workflows for precision medicine.

2 MiR-10a-5p promotes PDAC cell migration and invasion. a MiR-10a-5p overexpression promoted T3M4 and AsPC-1 cell migration, while miR-10a-5p knockdown decreased Su86.86 and AsPC-1 cell migration; b miR-10a-5p overexpression promoted T3M4 and AsPC-1 cell invasion, while miR-10a-5p knockdown decreased Su86.86 and AsPC-1 cell invasion; c miR-10a-5p expression up-regulation decreased E-cadherin and Caudin-1 protein levels while increasing Vimentin, Slug and Snail levels, as determined by using western blotting. d The relative intensity of the grayscale band values revealed the changes with miR-10a-5p overexpression or knockdown in PDAC cells; the data are presented as the means ± SD (Student's t-test; *, P < 0.05) Reference 1 Xiong G, Huang H, Feng M. MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma. Guangbing Xiong, Hua Huang, Mengyu Feng and Gang Yang contributed equally to this work. [Extracted from the article]

Background: By regulating target genes, microRNAs play essential roles in carcinogenesis and drug resistance in human pancreatic ductal adenocarcinoma (PDAC). Previous studies have shown that microRNA-10a-5p (miR-10a-5p) is overexpressed in PDAC and acts as an oncogene to promote the metastatic behavior of PDAC cells. However, the role of miR-10a-5p in PDAC chemoresistance remains unclear. Methods: The effects of miR-10a-5p on biological behaviors were analyzed. MiR-10a-5p and TFAP2C levels in tissues were detected, and the clinical value was evaluated. Results: We found that miR-10a-5p is up-regulated in gemcitabine-resistant PDAC cells and enhances PDAC cell gemcitabine resistance in vitro and vivo. Meanwhile, we also determined that miR-10a-5p promotes the migratory and invasive ability of PDAC cells. Next, we confirmed that transcription factor activating protein 2 gamma (TFAP2C) is a target of miR-10a-5p, and TFAP2C overexpression resensitizes PDAC cells to gemcitabine, which is initiated by miR-10a-5p. Further studies revealed that TFAP2C also decreased PDAC cell migration and invasion capability. Finally, survival analysis demonstrated that high miR-10a-5p expression levels and low TFAP2C expression levels were both independent adverse prognostic factors in patients with PDAC. Conclusion: Together, these results indicate that miR-10a-5p/TFAP2C may be new therapeutic target and prognostic marker in PDAC. [ABSTRACT FROM AUTHOR]