LHX2 Enhances the Malignant Phenotype of Esophageal Squamous Cell Carcinoma by Upregulating the Expression of SERPINE2

Xukun Li; Xueling Wu; Hongyan Chen; Zhihua Liu; Huan He; Luhua Wang

doi:10.3390/genes13081457

LHX2 Enhances the Malignant Phenotype of Esophageal Squamous Cell Carcinoma by Upregulating the Expression of SERPINE2

Genes (Basel). 2022 Aug 16;13(8):1457. doi: 10.3390/genes13081457.

Authors

Xukun Li^{1

2}, Xueling Wu², Hongyan Chen², Zhihua Liu², Huan He², Luhua Wang¹

Affiliations

¹ Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China.
² The State Key Laboratory of Molecular 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.

Abstract

LHX2 dysregulations have been found to present in cancers, but the function of LHX2 in esophageal squamous cell carcinoma (ESCC) remains unknown. Here, we report that LHX2 was upregulated in ESCC tissues in comparison to the LHX2 levels in adjacent normal tissues. Loss- and gain-of-function experiments demonstrated that the knockdown of LHX2 markedly inhibited ESCC cells' proliferation, migration, invasion, tumor growth and metastasis, whereas the overexpression of LHX2 had the opposite effects. A mechanistic investigation revealed that LHX2 bound to the promoter of SERPINE2 gene and transcriptionally regulated the expression of SERPINE2. Collectively, LHX2 facilitates ESCC tumor progression, and it could be a potential therapeutic target for ESCC.

Keywords: ESCC; LHX2; SERPINE2; oncogene; tumor progression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation / genetics
Esophageal Neoplasms* / genetics
Esophageal Neoplasms* / pathology
Esophageal Squamous Cell Carcinoma* / genetics
Gene Expression Regulation, Neoplastic
Humans
LIM-Homeodomain Proteins / genetics
LIM-Homeodomain Proteins / metabolism
Neoplasm Invasiveness / genetics
Phenotype
Serpin E2 / genetics
Serpin E2 / metabolism
Transcription Factors / genetics

Substances

LHX2 protein, human
LIM-Homeodomain Proteins
SERPINE2 protein, human
Serpin E2
Transcription Factors

Grants and funding

This work was supported by National Natural Science Foundation of China (82030089, 82002976, 81872227), CAMS Innovation Fund for Medical Sciences (2021-I2M-1-018, 2021-I2M-1-067), Shenzhen Key Medical Discipline Construction Fund (No. SZXK013), Sanming Project of Medicine in Shenzhen (No. SZSM201812062) and Non-Profit Central Research Institute Fund of CAMS (2018RC310009).