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ACTL8 高表达预示着不良预后,并加速头颈部鳞状细胞癌的细胞进展。

High expression of ACTL8 is poor prognosis and accelerates cell progression in head and neck squamous cell carcinoma.

机构信息

Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.

出版信息

Mol Med Rep. 2019 Feb;19(2):877-884. doi: 10.3892/mmr.2018.9716. Epub 2018 Dec 3.

Abstract

Actin‑like protein 8 (ACTL8) is a member of the cancer‑testis antigens (CTA) family, which is mainly localized in the cytoplasm and generally expressed in the testis. The association between ACTL8 and various types of cancer, including glioblastoma and breast cancer, has previously been demonstrated. However, whether ACTL8 is involved in the development of head and neck squamous cell carcinoma (HNSCC) remains unknown. In the present study, the expression of ACTL8 in patients with HNSCC was analyzed in The Cancer Genome Atlas (TCGA) dataset, clinical tissues and cell lines. Correlations between the expression levels of ACTL8 and HNSCC clinical outcomes were analyzed with the Kaplan‑Meier method and the Cox proportional hazards model. Cell Counting Kit‑8, plate colony formation and Transwell assays were used to assess the effects of ACTL8 interference on the proliferation, migration and invasion of HNSCC PCI‑13 cells. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to evaluate the expression levels of ACTL8 in PCI‑13 cells. Furthermore, alterations in the expression levels of key proteins in the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K)/RAC‑α protein kinase B (AKT) signaling pathway were determined by western blotting. Increased expression of ACTL8 in HNSCC was observed in TCGA dataset, cancerous tissue samples and HNSCC cell line. Cox regression analysis indicated that ACTL8 expression could be regarded as an independent prognostic factor for HNSCC, since increased expression of ACTL8 was associated with a poor prognosis. Knocking down ACTL8 markedly inhibited the proliferation, invasion and migration of PCI‑13 cells. Additionally, activation of the PI3K/AKT signaling pathway was suppressed by reduced expression levels of certain key proteins in this pathway. The present data indicate that ACTL8 serves a role in the progression and clinical prognosis of HNSCC. Therefore, ACTL8 may be a potential prognostic marker and novel therapeutic target for HNSCC.

摘要

肌动蛋白样蛋白 8(ACTL8)是癌症睾丸抗原(CTA)家族的成员,主要定位于细胞质,通常在睾丸中表达。ACTL8 与包括神经胶质瘤和乳腺癌在内的各种类型的癌症之间的关联以前已经得到证明。然而,ACTL8 是否参与头颈部鳞状细胞癌(HNSCC)的发展尚不清楚。在本研究中,在癌症基因组图谱(TCGA)数据集、临床组织和细胞系中分析了 HNSCC 患者中 ACTL8 的表达。采用 Kaplan-Meier 方法和 Cox 比例风险模型分析了 ACTL8 表达水平与 HNSCC 临床结局之间的相关性。使用细胞计数试剂盒-8、平板集落形成和 Transwell 测定法评估了 ACTL8 干扰对 HNSCC PCI-13 细胞增殖、迁移和侵袭的影响。逆转录-定量聚合酶链反应和蛋白质印迹法用于评估 PCI-13 细胞中 ACTL8 的表达水平。此外,通过蛋白质印迹法测定了磷脂酰肌醇-4,5-二磷酸 3-激酶(PI3K)/RAC-α 蛋白激酶 B(AKT)信号通路中关键蛋白表达水平的变化。在 TCGA 数据集、癌组织样本和 HNSCC 细胞系中观察到 HNSCC 中 ACTL8 的表达增加。Cox 回归分析表明,ACTL8 表达可以被视为 HNSCC 的独立预后因素,因为 ACTL8 的高表达与预后不良相关。敲低 ACTL8 可显著抑制 PCI-13 细胞的增殖、侵袭和迁移。此外,通过降低该通路中某些关键蛋白的表达水平,抑制了 PI3K/AKT 信号通路的激活。本研究数据表明,ACTL8 在 HNSCC 的进展和临床预后中发挥作用。因此,ACTL8 可能是 HNSCC 的潜在预后标志物和新型治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9623/6323208/1ae92ccd97b4/MMR-19-02-0877-g00.jpg

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