探究 SETD6 在肺腺癌中的功能作用。

Investigating the functional role of SETD6 in lung adenocarcinoma.

机构信息

Department of Pharmacy, Dermatology Hospital, Southern Medical University, Guangzhou, China.

Department of Pharmacy, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

出版信息

BMC Cancer. 2023 Jan 6;23(1):18. doi: 10.1186/s12885-022-10476-9.

DOI:10.1186/s12885-022-10476-9

PMID:36604642

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9817333/

Abstract

BACKGROUND

SET domain containing 6 (SETD6) has been shown to be upregulated in multiple human cancers and can promote malignant cell survival. However, expression and function of SETD6 in lung adenocarcinoma (LUAD) remains unaddressed. This study aimed to demonstrate the expression pattern, biological roles and potential mechanisms by which SETD6 dysregulation is associated with LUAD.

METHODS

The expression level of SETD6 was evaluated in LUAD clinical specimens and its correlation with clinical parameters were analyzed. In vitro, gain-of-function and loss-of-function experiments were performed to evaluate the effects of SETD6 on cell proliferation, apoptosis, migration, and colony formation of LUAD cell line A549. Western-blot was performed to investigate the involvement of nuclear factor-κB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways as downstream signaling of SETD6 in LUAD cells.

RESULTS

Compared with non-tumorous tissues, SETD6 was overexpressed in tumor tissues, and its overexpression significantly correlates with higher rates of regional lymph node metastasis and poor prognosis in patients with LUAD. In A549 cell line, SETD6 overexpression could promote cell proliferation, migration, colony formation and inhibit cell apoptosis, whereas SETD6 knockdown caused the opposite effects. Furthermore, we demonstrated that the mechanisms underlying the effect of SETD6 on LUAD biological behaviors may be through its interaction with NF-κB and Nrf2 signaling pathways.

CONCLUSIONS

SETD6, which is highly expressed in LUAD tumor tissues, plays an important role in promoting the malignant behaviors of LUAD via likely the NF-κB and Nrf2 signaling pathways.

摘要

背景

SET 结构域包含 6（SETD6）已在多种人类癌症中被证明上调，并能促进恶性细胞存活。然而，SETD6 在肺腺癌（LUAD）中的表达和功能仍未得到解决。本研究旨在证明 SETD6 失调与 LUAD 相关的表达模式、生物学作用和潜在机制。

方法

评估 SETD6 在 LUAD 临床标本中的表达水平，并分析其与临床参数的相关性。在体外，通过过表达和敲低实验来评估 SETD6 对 LUAD 细胞系 A549 细胞增殖、凋亡、迁移和集落形成的影响。Western blot 用于研究核因子-κB（NF-κB）和核因子红细胞 2 相关因子 2（Nrf2）途径作为 SETD6 在 LUAD 细胞中的下游信号转导的参与情况。

结果

与非肿瘤组织相比，肿瘤组织中 SETD6 表达上调，其过表达与 LUAD 患者区域淋巴结转移率较高和预后不良显著相关。在 A549 细胞系中，SETD6 过表达可促进细胞增殖、迁移、集落形成并抑制细胞凋亡，而 SETD6 敲低则产生相反的效果。此外，我们证明了 SETD6 对 LUAD 生物学行为的影响的机制可能是通过其与 NF-κB 和 Nrf2 信号通路的相互作用。