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Bcl2 相关抗凋亡基因 2 在口腔癌中的过表达促进细胞增殖,并与不良预后相关。

Over-expression of Bcl2-associated athanogene 2 in oral cancer promotes cellular proliferation and is associated with poor prognosis.

机构信息

Dental Department, Daqing Oilfield General Hospital, Daqing City, Heilongjiang Province, 163001, China.

Endocrine Department, Daqing Oilfield General Hospital, Daqing City, Heilongjiang Province, 163001, China.

出版信息

Arch Oral Biol. 2019 Jun;102:164-170. doi: 10.1016/j.archoralbio.2019.04.015. Epub 2019 Apr 29.

Abstract

OBJECTIVE

The aim of the present study was to state the role of BAG2 in oral squamous cell carcinomas (OSCC).

DESIGN

Expression data of BAG2 in OSCC tissues were extracted from Oncomine and TCGA database. Expression levels of BAG2 mRNA and protein were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot assay. The Kaplan-Meier method was conducted to evaluate the overall survival of OSCC patients. Small interfering RNAs (siRNAs) strategy was used to confirm the effect of BAG2 expression on proliferative, invasive, migrated capacities of OSCC cells by Cell Counting kit-8 (CCK-8), colon formation assay, wound healing and transwell assay.

RESULTS

Our results showed that BAG2 expression was up-regulated in oral squamous cell carcinomas tissues. Compared with OSCC patients with low BAG2 expression, poorer overall survival rate was found in OSCC patients with high BAG2 expression. Furthermore, proliferation, invasion and migration of HO-1-N-1 cells were significantly inhibited because of the knockdown of BAG2. Transfection of si-BAG2 has no impacts on proliferation in HNOEC cells. Inhibition of BAG2 downregulated the expression of relevant proteins, such as proliferating cell nuclear antigen (PCNA), c-Myc, matrix metalloproteinase-2 (MMP-2) and Vimentin. Additionally, the expression levels of the important protein phosphorylation (p-ERK1/2 and p-MEK) in mitogen-activated protein kinase (MAPK) pathway were reduced in HO-1-N-1 cells transfected with si-BAG2.

CONCLUSIONS

High-regulated BAG2 is related to poor prognosis and could promote proliferation, invasion and migration of OSCC cells by activating the MAPK signaling pathway. Thus, BAG2 may be a potential target for OSCC therapy.

摘要

目的

本研究旨在阐述 BAG2 在口腔鳞状细胞癌(OSCC)中的作用。

设计

从 Oncomine 和 TCGA 数据库中提取 BAG2 在 OSCC 组织中的表达数据。采用定量逆转录聚合酶链反应(qRT-PCR)和 Western blot 检测 BAG2 mRNA 和蛋白的表达水平。采用 Kaplan-Meier 法评估 OSCC 患者的总生存率。采用小干扰 RNA(siRNA)策略,通过细胞计数试剂盒-8(CCK-8)、集落形成实验、划痕愈合实验和 Transwell 实验,确认 BAG2 表达对 OSCC 细胞增殖、侵袭和迁移能力的影响。

结果

我们的结果表明,BAG2 在口腔鳞状细胞癌组织中表达上调。与 BAG2 低表达的 OSCC 患者相比,BAG2 高表达的 OSCC 患者总生存率较低。此外,由于 BAG2 的敲低,HO-1-N-1 细胞的增殖、侵袭和迁移能力显著受到抑制。si-BAG2 的转染对 HNOEC 细胞的增殖没有影响。BAG2 的抑制下调了相关蛋白的表达,如增殖细胞核抗原(PCNA)、c-Myc、基质金属蛋白酶-2(MMP-2)和波形蛋白。此外,转染 si-BAG2 后,HO-1-N-1 细胞中丝裂原激活蛋白激酶(MAPK)通路中重要蛋白磷酸化(p-ERK1/2 和 p-MEK)的表达水平降低。

结论

高表达的 BAG2 与预后不良有关,并可通过激活 MAPK 信号通路促进 OSCC 细胞的增殖、侵袭和迁移。因此,BAG2 可能是 OSCC 治疗的潜在靶点。

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