Suppression of tumorigenesis in LUAD by LRP1B through regulation of the IL-6-JAK-STAT3 pathway

被引：0

作者：

Ye, Chunshui ^{[1
]}

Chong, Wei ^{[1
,2
,3
]}

Liu, Yuan ^{[1
]}

Zhu, Xingyu ^{[1
,2
,3
]}

Ren, Huicheng ^{[1
,2
,3
]}

Xu, Kang ^{[1
,2
,3
]}

Xie, Xiaozhou ^{[1
,2
,3
]}

Du, Fengying ^{[1
,2
,3
]}

Zhang, Zihao ^{[1
]}

Wang, Mingfei ^{[1
]}

Ma, Tianrong ^{[1
,2
,3
]}

Shang, Liang ^{[1
,2
,3
]}

Li, Leping ^{[1
,2
,3
]}

Chen, Hao ^{[4
]}

机构：

[1] Shandong Univ, Shandong Prov Hosp, Dept Gastrointestinal Surg, Jinan 250021, Shandong, Peoples R China

[2] Shandong First Med Univ, Shandong Prov Hosp, Key Lab Engn Shandong Prov, Jinan, Shandong, Peoples R China

[3] Shandong First Med Univ & Shandong Acad Med Sci, Med Sci & Technol Innovat Ctr, Jinan, Shandong, Peoples R China

[4] Shandong Univ, Qilu Hosp, Clin Res Ctr, Clin Epidemiol Unit, Jinan 250012, Shandong, Peoples R China

来源：

AMERICAN JOURNAL OF CANCER RESEARCH | 2023年 / 13卷 / 07期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

LRP1B; inflammation; IL-6; JAK-STAT3; LUAD; CELL LUNG-CANCER; EXPRESSION; GENE; IL-6; MIGRATION; BLOCKADE; PROTEIN; GROWTH; STAT3;

D O I：

暂无

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Lung adenocarcinoma (LUAD) is the most common type of lung cancer. LRP1B was initially identified as a cancer suppressor in several cancers. However, the potential biological phenotypes and molecular mechanisms of LRP1B in LUAD have not been fully investigated. In our study, we showed that the expression of LRP1B in LUAD tissues was lower than that in normal tissues. Knockdown of LRP1B markedly enhanced malignancy of LUAD cells. Genomic analysis indicated that the population expressing low-levels of LRP1B had higher genomic instability, which accounted for a larger proportion of aneuploidy and inflammation subtyping. Enrichment analysis of bulk and cell-line transcriptomic data both showed that the low expression of LRP1B could induce the activation of IL-6-JAK-STAT3, chemokine, cytokine, and other inflammation signaling pathways. Moreover, our findings revealed that knockdown LRP1B enhanced the secretion of IL-6 and IL-8, as confirmed by ELISA assays. Further validation using PCR and WB confirmed that downregulation of LRP1B mRNA significantly upregulated the activity of the IL-6JAK-STAT3 pathway. Collectively, this study highlights LRP1B as a tumor suppressor gene and reveals that LRP1B knockdown promotes malignant progression in LUAD by inducing inflammation through the IL-6-JAK-STAT3 pathway.

引用

页码：2886 / +

页数：24