LncRNA625 inhibits STAT1-mediated transactivation potential in esophageal cancer cells

Huang Guo-Wei; Li Chun-Quan; Liao Lian-Di; Jiao Ji-Wei; Long Lin; Ding Ji-Yu; Guo Jin-Cheng; Li En-Min; Xu Li-Yan

doi:10.1016/j.biocel.2019.105626

LncRNA625 inhibits STAT1-mediated transactivation potential in esophageal cancer cells

Int J Biochem Cell Biol. 2019 Dec:117:105626. doi: 10.1016/j.biocel.2019.105626. Epub 2019 Oct 9.

Authors

Huang Guo-Wei¹, Li Chun-Quan², Liao Lian-Di³, Jiao Ji-Wei⁴, Long Lin⁴, Ding Ji-Yu⁴, Guo Jin-Cheng⁴, Li En-Min⁵, Xu Li-Yan⁶

Affiliations

¹ Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, 515041, PR China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China.
² School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, 163319, PR China.
³ Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, 515041, PR China.
⁴ The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, 515041, PR China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China.
⁵ The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, 515041, PR China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China. Electronic address: nmli@stu.edu.cn.
⁶ Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China; The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, 515041, PR China. Electronic address: lyxu@stu.edu.cn.

PMID: 31605752
DOI: 10.1016/j.biocel.2019.105626

Abstract

Although Signal transducer and activator of transcription 1 (STAT1)-mediated transactivation potential is inhibited in cancer cells, the mechanism is poorly understood. In the present study, we implicated long non-coding RNA lncRNA625 in the inhibition of STAT1 activity. LncRNA625 knockdown up-regulated STAT1-mediated transcription and resulted in an increase of STAT1-mediated expression of IFITM2. Conversely, lncRNA625 upregulation inhibited STAT1 reporter activity. Mechanistically, lncRNA625 inhibited STAT1 binding to the promoter of IFITM2 in both untreated cells and following interferon-gamma (IFN-γ) stimulation. LncRNA625 interacted with the DNA-binding (DB) domain of STAT1 and promoted STAT1 interaction with T-cell protein tyrosine phosphatase TC45 to dephosphorylate pSTAT1. Taken together, the results show that lncRNA625 inhibits STAT1-mediated transactivation potential by causing formation of STAT1-TC45 complexes, resulting in STAT1 dephosphorylation.

Keywords: IFITM2; Interaction; LncRNA625; STAT1; TC45.

Publication types

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

MeSH terms

Cell Line, Tumor
Esophageal Neoplasms / genetics*
Esophageal Neoplasms / metabolism
Esophageal Squamous Cell Carcinoma / genetics*
Esophageal Squamous Cell Carcinoma / metabolism
HEK293 Cells
HeLa Cells
Humans
Interferon-gamma / pharmacology
K562 Cells
Phosphorylation
Promoter Regions, Genetic
Protein Tyrosine Phosphatase, Non-Receptor Type 2 / genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 2 / metabolism
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
STAT1 Transcription Factor / antagonists & inhibitors*
STAT1 Transcription Factor / genetics
STAT1 Transcription Factor / metabolism
Signal Transduction
Transcription, Genetic
Transcriptional Activation
Transfection

Substances

RNA, Long Noncoding
STAT1 Transcription Factor
STAT1 protein, human
Interferon-gamma
Protein Tyrosine Phosphatase, Non-Receptor Type 2