Down regulation of miR-143 promotes radiation – Induced thymic lymphoma by targeting B7H1. (5th October 2017)

• Record Type: Journal Article
• Authors: Zhao, Hainan; Cheng, Ying; Dong, Suhe; Du, Jicong; Gao, Fu; Sun, Ding; Cui, Jianguo; Ni, Jin; Cai, Jianming
• Is Part Of: Toxicology letters. Volume 280(2017)
• Page Start: 116
• Page End: 124
• Publication Date: 2017-10-05
• Subjects: Radiation carcinogenesis -- Radiation induced thymic lymphoma (RITL) -- miR-143 -- B7H1 -- Tumor therapy; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2017.07.891
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: MiR-143 is down-regulated while B7H1 is up-regulated in RITL model. Overexpression of miR-143 inhibited cell proliferation, increased apoptosis while down-regulation promoted proliferation and reduced apoptosis. B7H1 protein expression levels are inversely correlated with miR-143 expression levels in RITL samples. MiR-143 targets B7H1 in a 3′UTR dependent manner. Over-expression of pre-miR-143 reduced tumorigenesis in vivo. And B7H1 partially rescued miR-143 mediated apoptosis in vitro. Induction of miR-143 or inhibition of B7H1 may be novel therapeutic methods for RITL. Abstract: MicroRNA-143 has been implicated in tumor metastasis by directly targeting Bcl-2, and microRNA-143 expression is decreased in several human tumors. However, the expression and targets of miR-143 in radiation carcinogenesis remain unclear. We found that the expression of miR-143 is down-regulated and the expression of B7H1 (Pdcd1) is up-regulated in radiation-induced thymic lymphoma model in BALB/c mice. Additionally, overexpression of miR-143 strongly inhibited cell proliferation and increased cell apoptosis and its down-regulation promoted cell proliferation and reduced cell apoptosis. We also determined that there is an inverse correlation between miR-143 expression and B7H1 protein expression in radiation-induced thymic lymphoma samples, and miR-143 targets B7H1 in a 3′UTR-dependent manner. In addition, we found that adenovirus over-expression of pre-miR-143 reduced tumorigenesis in vivo. Finally, we conclude that down-regulated expression of miR-143 and up-regulation of its direct target B7H1 may indicate a novel therapeutic method for radiation-induced thymic lymphoma by increased expression of miR-143 or inhibition of B7H1.