Department of Oncology, Affiliated Zhongshan Hospital, Dalian University, Dalian, P.R. China.
Department of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University, Dalian, P.R. China.
IUBMB Life. 2021 Apr;73(4):690-704. doi: 10.1002/iub.2450. Epub 2021 Feb 23.
Dysfunction of histone deacetylase 10 (HDAC10) has been suggested in the carcinogenesis of cervical cancer (CC). However, its association with microRNAs (miRNAs) in CC remains exclusive. Hence, this study aims to probe the role of HDAC10 in regulating CC cell proliferation, migration, and invasion and its correlation with the screened-out miRNA target. Microarray analysis and RT-qPCR revealed that HDAC10 expressed poorly in CC cells relative to human immortalized endocervical cells (End1/E6E7). Moreover, HDAC10 downregulation predicted poor survival for patients with CC. Overexpression of HDAC10 reduced CC cell biological activities in vitro and tumor growth and lung metastases in vivo. miR-223, upregulated in CC, was regulated by HDAC10 through histone acetylation, while miR-223 inhibited the effects of HDAC10 overexpression in CC. miR-223 targeted the 3'-UTR of thioredoxin interacting protein (TXNIP) and suppressed its expression, leading to increased CC development in vitro and in vivo. TXNIP overexpression impaired Wnt/β-catenin pathway activity in CC cells.
组蛋白去乙酰化酶 10（HDAC10）功能障碍已被认为与宫颈癌（CC）的发生有关。然而，其与 CC 中 microRNAs（miRNAs）的关联尚属首次报道。因此，本研究旨在探讨 HDAC10 在调节 CC 细胞增殖、迁移和侵袭中的作用及其与筛选出的 miRNA 靶标的相关性。微阵列分析和 RT-qPCR 显示，HDAC10 在 CC 细胞中的表达相对人永生化宫颈内膜细胞（End1/E6E7）较低。此外，HDAC10 的下调预示着 CC 患者的预后不良。HDAC10 的过表达降低了 CC 细胞的体外生物学活性以及体内肿瘤生长和肺转移。miR-223 在 CC 中上调，受 HDAC10 通过组蛋白乙酰化调节，而 miR-223 抑制了 CC 中 HDAC10 过表达的作用。miR-223 靶向硫氧还蛋白相互作用蛋白（TXNIP）的 3'-UTR 并抑制其表达，导致体外和体内 CC 发育增加。TXNIP 的过表达削弱了 CC 细胞中的 Wnt/β-catenin 通路活性。
