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Involvement of elevated ASF1B in the poor prognosis and tumorigenesis in pancreatic cancer

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Abstract

Anti-silencing function 1B (ASF1B) has been reported to be associated with the occurrence of many kinds of tumors. However, the biological effect and action mechanism of ASF1B in pancreatic cancer (PC) tumorigenesis remain unclear. The expression and prognosis value of ASF1B in PC were analyzed using GEPIA, GEO, and Kaplan–Meier plotter databases. The diagnostic value of ASF1B in PC was determined by receiver operating characteristic curve. The relationship between ASF1B expression and the clinical feathers in PC was investigated based on TCGA. qRT-PCR and western blot analyses were used to measure ASF1B expression in PC cells. Cell proliferation was evaluated by MTT and EdU assays, and apoptosis was examined by TUNEL and caspase-3 activity assays. Western blot analysis was utilized to detect the expression of proliferating cell nuclear antigen (PCNA), cyclin D1, Bax, Bcl-2, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling proteins. ASF1B was overexpressed in several digestive cancers, including PC. Upregulated ASF1B was correlated with the poor prognosis and clinical features in PC patients. The area under the curve (AUC) value of ASF1B was 0.990. ASF1B was also overexpressed in PC cells. ASF1B silencing inhibited PC cell proliferation, promoted apoptosis, and increased caspase-3 activity, which were accompanied by the reduction of PCNA and cyclin D1 expression and increase of the ratio of Bax/Bcl-2 expression. Additionally, ASF1B silencing suppressed the PI3K/Akt pathway and 740Y-P treatment partially abolished the effects of ASF1B knockdown on PC cells. In conclusion, ASF1B silencing retarded proliferation and promoted apoptosis in PC cells by inactivation of the PI3K/Akt pathway.

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Authors and Affiliations

  1. Department of Hepatobiliary and Pancreatic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Shenyang, 110042, Liaoning, China

    Kun Wang, Zhiqiang Hao, Xibo Fu, Wenxin Li, Ao Jiao & Xiangdong Hua

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  1. Kun Wang
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  2. Zhiqiang Hao
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  3. Xibo Fu
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  4. Wenxin Li
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  5. Ao Jiao
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  6. Xiangdong Hua
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Contributions

KW, ZH, and XF conducted the experiments. XF, WL, and AJ supervised the data collection and analyzed the data. ZH and XH designed the study and prepared the manuscript. All authors have read and approved the manuscript.

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Correspondence to Xiangdong Hua.

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Wang, K., Hao, Z., Fu, X. et al. Involvement of elevated ASF1B in the poor prognosis and tumorigenesis in pancreatic cancer. Mol Cell Biochem 477, 1947–1957 (2022). https://doi.org/10.1007/s11010-022-04404-5

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  • DOI: https://doi.org/10.1007/s11010-022-04404-5

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