Gadd45a gene silencing by RNAi promotes cell proliferation and inhibits apoptosis and senescence in skin squamous cell carcinoma through the p53 signaling pathway.

作者: Li-Qian Liu , Fu-Jun Tian , Ying Xiong , Yan Zhao , Jian-Bo Song

DOI: 10.1002/JCP.26588

关键词:

摘要: Skin squamous cell carcinoma (SCC) is generally considered as nonaggressive lesions and mainly caused by ultraviolet (UV) radiation. Gadd45a a key component protecting skin against UV-induced tumors. For that, the study aims to investigate mechanism of gene silencing on proliferation, apoptosis, senescence in nude mice with SCC through p53 signaling pathway. Healthy was collected normal group 40 mouse models were successfully established model group, which sub-divided into five groups. The incidence, size, weight tumor observed. mRNA expression Gadd45a, Cyclin B1, MMP-2, Bcl-2, Bax determined RT-qPCR. Cell viability, cycle detected MTT assay, flow cytometry, β-galactosidase staining, respectively. levels inflammatory factors vascular endothelial growth factor (VEGF) using ELISA. protein rate mutant immunohistochemistry. Mice transfected siGadd45a showed increased weight. Cells decrease Bax; increase p53, IL-1α, IL-1β, IL-6, TNF-α, VEGF. apoptosis inhibited, while viability proliferation promoted after treatment. results reveal that increases reduces pathway SCC.

参考文章(29)
Faraz A. Sultan, J. David Sweatt, The Role of the Gadd45 Family in the Nervous System: A Focus on Neurodevelopment, Neuronal Injury, and Cognitive Neuroepigenetics Advances in Experimental Medicine and Biology. ,vol. 793, pp. 81- 119 ,(2013) , 10.1007/978-1-4614-8289-5_6
Michael J McKay, Advanced skin squamous cell carcinoma: role of radiotherapy. Australian Family Physician. ,vol. 43, pp. 33- ,(2014)
Enrico De Smaele, Francesca Zazzeroni, Salvatore Papa, Dung U. Nguyen, Rongguan Jin, Joy Jones, Rong Cong, Guido Franzoso, Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signalling Nature. ,vol. 414, pp. 308- 313 ,(2001) , 10.1038/35104560
Xiao-Ying Zhang, Zhen-Guang Wang, Cheng-Jun Zhou, Xun-Qu, Cheng-Qin Wang, Gui-Xiang Liu, Expression of growth arrest and DNA damage inducible 45a in human oral squamous cell carcinoma is associated with tumor progression and clinical outcome. Journal of Cancer Research and Therapeutics. ,vol. 10, pp. 108- ,(2014) , 10.4103/0973-1482.145811
Ming Dong, Qi Dong, Hao Zhang, Jianping Zhou, Yulin Tian, Yuting Dong, Expression of Gadd45a and p53 proteins in human pancreatic cancer: Potential effects on clinical outcomes Journal of Surgical Oncology. ,vol. 95, pp. 332- 336 ,(2007) , 10.1002/JSO.20684
Yuliya A. Sytnikova, Andriy V. Kubarenko, Andrea Schäfer, Alexander N. R. Weber, Christof Niehrs, Gadd45a Is an RNA Binding Protein and Is Localized in Nuclear Speckles PLOS ONE. ,vol. 6, ,(2011) , 10.1371/JOURNAL.PONE.0014500
Binfeng Lu, Anthony F Ferrandino, Richard A Flavell, Gadd45|[beta]| is important for perpetuating cognate and inflammatory signals in T cells Nature Immunology. ,vol. 5, pp. 38- 44 ,(2004) , 10.1038/NI1020
Jae Won Chang, Sung Un Kang, Yoo Seob Shin, Kang Il Kim, Seong Jin Seo, Sang Sik Yang, Jong-Soo Lee, Eunpyo Moon, Seung Jae Baek, Keunho Lee, Chul-Ho Kim, Non-thermal atmospheric pressure plasma induces apoptosis in oral cavity squamous cell carcinoma: Involvement of DNA-damage-triggering sub-G1 arrest via the ATM/p53 pathway Archives of Biochemistry and Biophysics. ,vol. 545, pp. 133- 140 ,(2014) , 10.1016/J.ABB.2014.01.022
HUIYONG WANG, YANQING ZHANG, JIANG QIAN, MINGUI ZHANG, XIANGNING WANG, Radiotherapy‑induced Gadd45a impairs lacrimal gland epithelial cell migration and proliferation. Molecular Medicine Reports. ,vol. 8, pp. 1049- 1054 ,(2013) , 10.3892/MMR.2013.1636