Oncogenic role of KIAA0101 interacting with proliferating cell nuclear antigen in pancreatic cancer - PubMed (original) (raw)
Oncogenic role of KIAA0101 interacting with proliferating cell nuclear antigen in pancreatic cancer
Masayo Hosokawa et al. Cancer Res. 2007.
Abstract
To isolate novel diagnostic markers and therapeutic targets for pancreatic cancer, we earlier did expression profile analysis of pancreatic cancer cells using a genome-wide cDNA microarray combined with microdissection. Among dozens of trans-activated genes in pancreatic cancer cells, this study focused on KIAA0101 whose overexpression in pancreatic cancer cells was validated by immunohistochemical analysis. KIAA0101 was previously identified as p15(PAF) [proliferating cell nuclear antigen (PCNA)-associated factor] to bind with PCNA; however, its function remains unknown. To investigate for the biological significance of KIAA0101 overexpression in cancer cells, we knocked down KIAA0101 by small interfering RNA (siRNA) in pancreatic cancer cells and found that the reduced expression by siRNA caused drastic attenuation of their proliferation as well as significant decrease in DNA replication rate. Concordantly, exogenous overexpression of KIAA0101 enhanced cancer cell growth, and NIH3T3 derivative cells expressing KIAA0101 revealed in vivo tumor formation, implying its growth-promoting and oncogenic property. We also showed that the expression of KIAA0101 was regulated tightly by the p53-p21 pathway. To consider the KIAA0101/PCNA interaction as a therapeutic target, we designed the cell-permeable 20-amino-acid dominant-negative peptide and found that it could effectively inhibit the KIAA0101/PCNA interaction and resulted in the significant growth suppression of cancer cells. Our results clearly implicated that suppression of the KIAA0101 and PCNA oncogenic activity, or the inhibition of KIAA0101/PCNA interaction, is likely to be a promising strategy to develop novel cancer therapeutic drugs.
Similar articles
- Variant 1 of KIAA0101, overexpressed in hepatocellular carcinoma, prevents doxorubicin-induced apoptosis by inhibiting p53 activation.
Liu L, Chen X, Xie S, Zhang C, Qiu Z, Zhu F. Liu L, et al. Hepatology. 2012 Nov;56(5):1760-9. doi: 10.1002/hep.25834. Epub 2012 Oct 14. Hepatology. 2012. PMID: 22576474 - The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b.
Simpson F, Lammerts van Bueren K, Butterfield N, Bennetts JS, Bowles J, Adolphe C, Simms LA, Young J, Walsh MD, Leggett B, Fowles LF, Wicking C. Simpson F, et al. Exp Cell Res. 2006 Jan 1;312(1):73-85. doi: 10.1016/j.yexcr.2005.09.020. Epub 2005 Nov 8. Exp Cell Res. 2006. PMID: 16288740 - PCNA-associated factor KIAA0101 transcriptionally induced by ELK1 controls cell proliferation and apoptosis in nasopharyngeal carcinoma: an integrated bioinformatics and experimental study.
Zhao H, Chen M, Wang J, Cao G, Chen W, Xu J. Zhao H, et al. Aging (Albany NY). 2020 Apr 9;12(7):5992-6017. doi: 10.18632/aging.102991. Epub 2020 Apr 9. Aging (Albany NY). 2020. PMID: 32275642 Free PMC article. - Variant 2 of KIAA0101, antagonizing its oncogenic variant 1, might be a potential therapeutic strategy in hepatocellular carcinoma.
Liu L, Liu Y, Chen X, Wang M, Zhou Y, Zhou P, Li W, Zhu F. Liu L, et al. Oncotarget. 2017 Jul 4;8(27):43990-44003. doi: 10.18632/oncotarget.16702. Oncotarget. 2017. PMID: 28410205 Free PMC article. - Proliferating cell unclear antigen-associated factor (PAF15): a novel oncogene.
Xie C, Yao M, Dong Q. Xie C, et al. Int J Biochem Cell Biol. 2014 May;50:127-31. doi: 10.1016/j.biocel.2014.02.024. Epub 2014 Mar 12. Int J Biochem Cell Biol. 2014. PMID: 24631643 Review.
Cited by
- Identification of Hub Genes to Regulate Breast Cancer Spinal Metastases by Bioinformatics Analyses.
He Y, Cao Y, Wang X, Jisiguleng W, Tao M, Liu J, Wang F, Chao L, Wang W, Li P, Fu H, Xing W, Zhu Z, Huan Y, Yuan H. He Y, et al. Comput Math Methods Med. 2021 May 12;2021:5548918. doi: 10.1155/2021/5548918. eCollection 2021. Comput Math Methods Med. 2021. PMID: 34055036 Free PMC article. - KIAA0101, a target gene of miR-429, enhances migration and chemoresistance of epithelial ovarian cancer cells.
Chen H, Xia B, Liu T, Lin M, Lou G. Chen H, et al. Cancer Cell Int. 2016 Sep 26;16:74. doi: 10.1186/s12935-016-0353-y. eCollection 2016. Cancer Cell Int. 2016. PMID: 27708548 Free PMC article. - Co-expression of mitosis-regulating genes contributes to malignant progression and prognosis in oligodendrogliomas.
Liu Y, Hu H, Zhang C, Wang H, Zhang W, Wang Z, Li M, Zhang W, Zhou D, Jiang T. Liu Y, et al. Oncotarget. 2015 Nov 10;6(35):38257-69. doi: 10.18632/oncotarget.5499. Oncotarget. 2015. PMID: 26468983 Free PMC article. - Combining tissue biomarkers with mpMRI to diagnose clinically significant prostate cancer. Analysis of 21 biomarkers in the PICTURE study.
Stopka-Farooqui U, Stavrinides V, Simpson BS, Qureshi H, Carmona Echevierra LM, Pye H, Ahmed Z, Alawami MF, Kay JD, Olivier J, Heavey S, Patel D, Freeman A, Haider A, Moore CM, Ahmed HU, Whitaker HC. Stopka-Farooqui U, et al. Prostate Cancer Prostatic Dis. 2024 Nov 22. doi: 10.1038/s41391-024-00920-1. Online ahead of print. Prostate Cancer Prostatic Dis. 2024. PMID: 39578642 - Regulation of Rad6/Rad18 Activity During DNA Damage Tolerance.
Hedglin M, Benkovic SJ. Hedglin M, et al. Annu Rev Biophys. 2015;44:207-28. doi: 10.1146/annurev-biophys-060414-033841. Annu Rev Biophys. 2015. PMID: 26098514 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous