Department of Gynecology and Obstetrics, The Fourth People's Hospital of Shaanxi, Xi'an, Shaanxi 710000, P.R. China.
Department of Obstetrics, The Northwest Women's and Children's Hospital, Xi'an, Shaanxi 710000, P.R. China.
Oncol Rep. 2019 Feb;41(2):1122-1130. doi: 10.3892/or.2018.6874. Epub 2018 Nov 20.
Homeobox A5 (HOXA5) is a member of the homeobox gene (HOX) family, which plays an important role in the development of various malignant tumors. Here, we speculated that HOXA5 has an effect on cervical cancer development. In our study, we aimed to explore the role and molecular mechanism of HOXA5 in regards to the cell proliferation and apoptosis in cervical cancer. We found that expression levels of HOXA5 measured by RT‑qPCR and western blot assays in cervical cancer cell lines and tissues were both significantly downregulated. We performed a gain‑of‑function experiment by the transfection with pcDNA.3.1‑HOXA5 in ME‑180 and HT‑3 cells to overexpress HOXA5, and the caspase‑3 activity measured by caspase‑3 activity assay kit and cell apoptosis detected by flow cytometry were obviously promoted. Meanwhile, cell proliferation tested by BrdU assay, invasion determined by Transwell and cell viability tested by MTT were inhibited. Moreover, protein kinase B (AKT) was activated by incubation with SC79 (AKT activator; 1 µg/ml) after HOXA5 overexpression, and reversed the effect of HOXA5 overexpression on p27 expression. Additionally, significant elevation of AKT activation measured by western blot analysis abrogated the effect of HOXA5 on caspase‑3 activity, cell apoptosis, proliferation, invasion and cell viability. Taken together, this study revealed that HOXA5 inhibits cervical cancer progression by regulating AKT/p27, proposing the potential role of HOXA5 in the prevention and treatment of cervical cancer.
Homeobox A5 (HOXA5) 是同源盒基因 (HOX) 家族的成员，在各种恶性肿瘤的发展中发挥着重要作用。在这里，我们推测 HOXA5 对宫颈癌的发展有影响。在我们的研究中，我们旨在探讨 HOXA5 在宫颈癌中对细胞增殖和凋亡的作用及其分子机制。我们发现，通过 RT-qPCR 和 Western blot 检测，HOXA5 在宫颈癌细胞系和组织中的表达水平均明显下调。我们通过 pcDNA.3.1-HOXA5 转染 ME-180 和 HT-3 细胞进行功能获得实验，以过表达 HOXA5，通过 caspase-3 活性检测试剂盒测量的 caspase-3 活性和通过流式细胞术检测的细胞凋亡明显增加。同时，通过 BrdU 测定法检测的细胞增殖、Transwell 测定法确定的侵袭以及通过 MTT 测定法检测的细胞活力均受到抑制。此外，HOXA5 过表达后用 SC79（AKT 激活剂；1μg/ml）孵育激活蛋白激酶 B (AKT)，并逆转了 HOXA5 过表达对 p27 表达的影响。此外，通过 Western blot 分析测量的 AKT 激活的显著升高消除了 HOXA5 对 caspase-3 活性、细胞凋亡、增殖、侵袭和细胞活力的影响。综上所述，本研究表明 HOXA5 通过调节 AKT/p27 抑制宫颈癌的进展，提示 HOXA5 在宫颈癌的预防和治疗中具有潜在作用。
