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同源结构域包含基因 10 通过激活白细胞介素-6/Janus 激酶 2/信号转导和转录激活因子 3 通路促进乳腺癌恶性行为。

Homeodomain-containing gene 10 contributed to breast cancer malignant behaviors by activating Interleukin-6/Janus kinase 2/Signal transducer and activator of transcription 3 pathway.

机构信息

Department of Breast Surgery, The First People's Hospital of LianYunGang, Lianyungang, Jiangsu Province, China.

出版信息

Bioengineered. 2022 Jan;13(1):1335-1345. doi: 10.1080/21655979.2021.2016088.

Abstract

Homeodomain‑containing gene 10 (HOXC10) has been identified as an oncogene in various malignancies. Nevertheless, the role and function of HOXC10 in breast cancer (BC) remain unclear. RT-qPCR and Western blot were used to detect the mRNA and protein levels of genes, respectively. CCK-8, transwell, and TUNEL assays were performed to evaluate cell viability, invasion, migration, and apoptosis of BC cells in vitro. The xenograft model was established to examine the effect of HOXC10 on tumor growth in vivo. Our results indicated that HOXC10 expression was increased in BC and correlated with an unsatisfactory prognosis. Functional assays indicated that HOXC10 overexpression promoted cell proliferation and metastasis, and suppressed cell apoptosis of BC, while HOXC10 knockdown showed opposite trends. Furthermore, in vitro and in vivo assays uncovered that HOXC10 promoted the tumorigenesis of BC via the activation of IL-6/JAK2/STAT3 signaling. Overall, our study revealed that HOXC10 could function as a tumor promotor in BC by upregulating IL-6 levels to activate the JAK2/STAT3 signaling pathway.

摘要

同源盒蛋白 10(HOXC10)已被鉴定为多种恶性肿瘤中的癌基因。然而,HOXC10 在乳腺癌(BC)中的作用和功能仍不清楚。使用 RT-qPCR 和 Western blot 分别检测基因的 mRNA 和蛋白水平。CCK-8、Transwell 和 TUNEL 测定分别用于评估 BC 细胞在体外的活力、侵袭、迁移和凋亡。建立异种移植模型以体内检测 HOXC10 对肿瘤生长的影响。我们的结果表明,HOXC10 在 BC 中表达增加,与预后不良相关。功能测定表明,HOXC10 过表达促进 BC 细胞的增殖和转移,并抑制细胞凋亡,而 HOXC10 敲低则呈现相反的趋势。此外,体外和体内实验表明,HOXC10 通过激活 IL-6/JAK2/STAT3 信号通路促进 BC 的肿瘤发生。总体而言,我们的研究表明,HOXC10 可以通过上调 IL-6 水平激活 JAK2/STAT3 信号通路,在 BC 中作为肿瘤促进因子发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2278/8805924/7a359e7c2cab/KBIE_A_2016088_F0001_OC.jpg

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