NR2F1-induced NR2F1-AS1 promotes esophageal squamous cell carcinoma progression via activating Hedgehog signaling pathway

Yaowen Zhang; Anping Zheng; Ruiping Xu; Fuyou Zhou; Anlin Hao; Haijun Yang; Pengyu Yang

doi:10.1016/j.bbrc.2019.09.015

NR2F1-induced NR2F1-AS1 promotes esophageal squamous cell carcinoma progression via activating Hedgehog signaling pathway

Biochem Biophys Res Commun. 2019 Nov 12;519(3):497-504. doi: 10.1016/j.bbrc.2019.09.015. Epub 2019 Sep 14.

Authors

Yaowen Zhang¹, Anping Zheng¹, Ruiping Xu², Fuyou Zhou³, Anlin Hao³, Haijun Yang⁴, Pengyu Yang¹

Affiliations

¹ The First Department of Radiation Oncology, Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, No.1, Huanbin Road, Anyang, 455000, Henan Province, China.
² The First Department of Radiation Oncology, Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, No.1, Huanbin Road, Anyang, 455000, Henan Province, China. Electronic address: ruizha8222@163.com.
³ Department of Thoracic Surgery, Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, No.1, Huanbin Road, Anyang, 455000, Henan Province, China.
⁴ Department of Pathology, Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, No.1, Huanbin Road, Anyang, 455000, Henan Province, China.

PMID: 31530388
DOI: 10.1016/j.bbrc.2019.09.015

Abstract

Emerging evidence has uncovered the extremely important roles of long noncoding RNAs (lncRNAs) in the progression of malignant tumors which includes numerous processes of gene regulation. LncRNA NR2F1-AS1 has been confirmed to have close correlation with the tumorigenesis of diverse cancers. However, the underlying regulatory function of it on esophageal squamous cell carcinoma (ESCC) progression is poorly known and thus needs more elucidations. In this study, a markedly elevated expression of NR2F1-AS1 was discovered in ESCC cells. Functional assays demonstrated that NR2F1-AS1 deficiency repressed ESCC progression. Molecular mechanism tests verified that knockdown of NR2F1-AS1 could lower the expression of GLI2 (a key protein molecule of Hedgehog signaling pathway) in ESCC. Additionally, NR2F1-AS1 was confirmed to facilitate ESCC progression via activation of Hedgehog signaling pathway. NR2F1-AS1 activated Hedgehog signaling pathway by regulating GLI2 to upregulate NR2F1 expression in ESCC. Besides, NR2F1 was testified to activate NR2F1-AS1 transcription in ESCC. Final rescue assays further demonstrated that NR2F1 upregulation could reverse the NR2F1-AS1 knockdown-mediated function on ESCC progression. Briefly, NR2F1-induced NR2F1-AS1 promotes ESCC progression through activation of Hedgehog signaling pathway.

Keywords: ESCC; GLI2; NR2F1; NR2F1-AS1.

MeSH terms

COUP Transcription Factor I / metabolism*
Cells, Cultured
Disease Progression
Esophageal Neoplasms / metabolism*
Esophageal Neoplasms / pathology
Esophageal Squamous Cell Carcinoma / metabolism*
Esophageal Squamous Cell Carcinoma / pathology
Hedgehog Proteins / metabolism*
Humans
RNA, Antisense / genetics
RNA, Antisense / metabolism*
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism*
Signal Transduction*

Substances

COUP Transcription Factor I
Hedgehog Proteins
NR2F1 protein, human
RNA, Antisense
RNA, Long Noncoding