被HLF调控的TNS1抑制前列腺癌的进展。
TNS1 regulated by HLF represses the progression of prostate cancer.
发表日期：2023 Sep 15
作者：
Hao Zhou, Fang Wang
来源：
Epigenetics & Chromatin
摘要：
肝白血病因子（HLF）是一种转录因子，在许多癌症中发生异常调节。本研究调查了HLF在前列腺癌（PCa）中的功能以及其与TNS1的关系。共收集了24个PCa患者的临床组织标本。建立了过表达HLF的DU145和PC3细胞系。与相邻组织相比，PCa组织中的HLF信号下调，与前列腺上皮细胞RWPE-1和前列腺基质细胞WPMY-1相比，DU145和PC3细胞中的HLF信号也下调。过表达HLF的PCa细胞系具有较低的增殖、迁移和侵袭活性，较高的细胞凋亡率，并且细胞有更多的在G0/G1期进行有丝分裂。HLF促进TNS1转录以激活p53通路。TNS1的耗竭逆转了HLF对PCa细胞和体内肿瘤生长和转移的抗肿瘤效果。总之，我们的研究发现表明，HLF通过上调TNS1表达和激活p53通路抑制PCa的发展，这可能为对抗PCa提供了新的策略。© 2023年作者。由牛津大学出版社代表英国环境变异学会出版。保留所有权利。有关权限，请发送电子邮件至：journals.permissions@oup.com。
Hepatic leukemia factor (HLF), a transcription factor, is dysregulated in many cancers. This study investigates the function of HLF in prostate cancer (PCa) and its relation to tensin 1 (TNS1). Clinical tissues were collected from 24 PCa patients. DU145 and PC3 cells overexpressing HLF were established. HLF signaling was downregulated in PCa tissues compared to adjacent tissues and in DU145 and PC3 cells compared to prostate epithelial cells RWPE-1 or prostate stromal cells (WPMY-1). PCa cell lines with overexpression of HLF had reduced proliferative, migratory, and invasive activity, increased apoptosis, and cell mitosis mostly in the G0/G1 phase. HLF induced the TNS1 transcription to activate the p53 pathway. Depletion of TNS1 reversed the anti-tumor effects of HLF on PCa cells and tumor growth and metastasis in vivo. In summary, our findings suggest that HLF suppressed PCa progression by upregulating TNS1 expression and inducing the p53 pathway activation, which might provide insights into novel strategies for combating PCa.© The Author(s) 2023. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.