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-233, upregulated in CC, was regulated by HDAC10 through histone acetylation, while miR-233 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.

中文翻译：

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组蛋白脱乙酰酶 10 通过新型 microRNA-223/TXNIP/Wnt/β-catenin 通路对宫颈癌发挥抗肿瘤作用


组蛋白脱乙酰酶 10 (HDAC10) 功能障碍已被认为与宫颈癌 (CC) 的发生有关。然而，它与 CC 中的 microRNA (miRNA) 的关联仍然是排他性的。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，相对于人永生化宫颈管细胞 (End1/E6E7)，HDAC10 在 CC 细胞中表达较差。此外，HDAC10 下调预示着 CC 患者的生存率较差。 HDAC10的过度表达降低了体外CC细胞的生物活性以及体内肿瘤生长和肺转移。 miR-233在CC中上调，受到HDAC10通过组蛋白乙酰化的调节，而miR-233抑制CC中HDAC10过表达的影响。 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 过表达会损害 CC 细胞中的 Wnt/β-catenin 通路活性。