SMC2 knockdown inhibits malignant progression of lung adenocarcinoma by upregulating BTG2 expression

Yan He; Yiyao Wang; Zhenyu Luo; Xue Zhang; Hua Bai; Jie Wang

doi:10.1016/j.cellsig.2024.111216

SMC2 knockdown inhibits malignant progression of lung adenocarcinoma by upregulating BTG2 expression

Cell Signal. 2024 May 8:120:111216. doi: 10.1016/j.cellsig.2024.111216. Online ahead of print.

Authors

Yan He¹, Yiyao Wang², Zhenyu Luo³, Xue Zhang¹, Hua Bai⁴, Jie Wang⁵

Affiliations

¹ National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; CAMS Key Laboratory of Translational Research on Lung Cancer, State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
² Department of Nursing Academy, Southwest Medical University, Luzhou, China.
³ Department of Clinical Medicine, Southwest Medical University, Luzhou, China.
⁴ National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; CAMS Key Laboratory of Translational Research on Lung Cancer, State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: baihua@cicams.ac.cn.
⁵ National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; CAMS Key Laboratory of Translational Research on Lung Cancer, State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: wangjie@cicams.ac.cn.

PMID: 38729325
DOI: 10.1016/j.cellsig.2024.111216

Abstract

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer worldwide. Structural maintenance of chromosomes 2 (SMC2) serves as a predictor of poor prognosis across various cancer types. This study aims to explore the role and underlying mechanisms of SMC2 in LUAD progression. The expression of SMC2 in LUAD tissues and its correlation with prognosis were analyzed by public databases. Knockdown of SMC2 was performed to assess the proliferation, migration and invasion ability of LUAD cells. Bulk RNA sequencing analysis identified enriched cellular pathways and remarkable upregulation of BTG anti-proliferation factor 2 (BTG2) expression after SMC2 knockdown in LUAD cells. Then, BTG2 was silenced to assess the malignant behavior of LUAD cells. Subcutaneous transplantation and intracranial tumor models of LUAD cells in BALB/c nude mice were established to assess the antineoplastic effect of SMC2 knockdown in vivo. Additionally, a lung metastasis model was created to evaluate the pro-metastatic effect of SMC2. Our findings indicated that SMC2 was upregulated in LUAD tissues and cell lines, with higher expression correlating with poor prognosis. SMC2 silencing suppressed the proliferation, migration and invasion ability of LUAD cells by upregulating BTG2 expression via p53 and inactivating ERK and AKT pathways. BTG2 silencing reversed the effects of SMC2 downregulation on malignant behaviors of LUAD cells and restored the phosphorylated ERK and AKT levels. Furthermore, SMC2 knockdown effectively prevented the formation of subcutaneous, intracranial and metastatic tumor in vivo, and upregulation of BTG2 expression after SMC2 knockdown was confirmed in tumor models. This study revealed that SMC2 knockdown restrained the malignant progression of LUAD through upregulation of BTG2 expression and inactivation of ERK and AKT pathways, and SMC2 could be a potential therapeutic target for LUAD treatment.

Keywords: BTG2; ERK/AKT signaling; LUAD; Progression; SMC2.