机构：[1]Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China[2]Department of Chemistry and Biochemistry, 101 Konneker Laboratories, Edison Biotechnology Institute, Athens, Ohio[3]Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China[4]Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China
UV induces CIRP expression and subsequent Stat3 activation, but the biological function and mechanism of CIRP and Stat3 in mediating UVB-induced skin carcinogenesis have not been fully elucidated. In this study, we demonstrate that CIRP is elevated in all tested melanoma and non-melanoma skin cancer cell lines; and the expression of CIRP is upregulated in keratinocytes after being irradiated with relatively low dose (<5 mJ/cm2 ), but not high dose (50 mJ/cm2 ), UVB acutely and chronically. The increased expression of CIRP, either induced by UVB or through overexpression, leads to resistance of keratinocytes to UVB-induced growth arrest and death; and reduced expression of CIRP by RNA knockdown sensitizes keratinocyte cells to the low dose UVB radiation. We also demonstrated that CIRP expression is required for the low dose UVB-induced Tyr705-phosphorylation, but not total amount, of Stat3. The p-Stat3 level is correlated with the expression levels of cyclin D1 and VEGF, two known downstream cell growth regulators of Stat3, as well as Bag-1/S, an apoptosis regulator. Inhibition of Stat3 DNA-binding activity by S3I-201 leads to a reduction of the p-Stat3 and Bag-1/S along with growth and survival of keratinocytes post-UVB; and the effect of S3I-201 on the UVB-irradiated cells can be partially inhibited by overexpression of CIRP or Bag-1/S. Furthermore, the overexpression of Bag-1/S can totally inhibit UVB-induced PARP cleavage and caspase 3 activation. The results presented above led us to propose that CIRP-p(705)Stat3 cascade promotes cell proliferation and survival post-UVB via upregulating the expression of cyclin D1 and Bag-1/S, respectively. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
基金：
National Natural Science Foundation of China;
Grant numbers: 31670952; 81261120383; Grant sponsor: Graduate
Scientific Research and Innovation Foundation of Chongqing, China;
Grant number: CYB16039; Grant sponsor: National Institutes of
Health; Grant number: RO1 CA86926
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|2 区生化与分子生物学2 区肿瘤学
最新[2023]版：
大类|2 区医学
小类|2 区生化与分子生物学3 区肿瘤学
第一作者：
第一作者机构：[1]Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China[2]Department of Chemistry and Biochemistry, 101 Konneker Laboratories, Edison Biotechnology Institute, Athens, Ohio[3]Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China[2]Department of Chemistry and Biochemistry, 101 Konneker Laboratories, Edison Biotechnology Institute, Athens, Ohio[*1]Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.[*2]Department of Chemistry and Biochemistry, and Edison Biotechnology Institute, 101 Konneker Laboratories, The Ridges, Bldg. 25, Athens, OH 45701.
推荐引用方式(GB/T 7714)：
Yi Liao,Jianguo Feng,Yi Zhang,et al.The mechanism of CIRP in inhibition of keratinocytes growth arrest and apoptosis following low dose UVB radiation.[J].Molecular carcinogenesis.2017,56(6):1554-1569.doi:10.1002/mc.22597.
APA：
Yi Liao,Jianguo Feng,Yi Zhang,Liling Tang&Shiyong Wu.(2017).The mechanism of CIRP in inhibition of keratinocytes growth arrest and apoptosis following low dose UVB radiation..Molecular carcinogenesis,56,(6)
MLA：
Yi Liao,et al."The mechanism of CIRP in inhibition of keratinocytes growth arrest and apoptosis following low dose UVB radiation.".Molecular carcinogenesis 56..6(2017):1554-1569
