STAT1-induced upregulation of lncRNA LINC01123 predicts poor prognosis and promotes the progression of endometrial cancer through miR-516b/KIF4A

Cell Cycle. 2020 Jun;19(12):1502-1516. doi: 10.1080/15384101.2020.1757936. Epub 2020 May 13.

Abstract

Long non-coding RNAs (lncRNAs) have been proposed as suppressors or promoters in many tumor processes. LncRNA LINC01123 (LINC01123) was a newly identified lncRNA which was firstly functionally analyzed in lung cancer. However, its expression and function in other tumor types were rarely reported. In this study, we firstly confirmed that LINC01123 was highly expressed in both endometrial cancer (EC) tissues and cell lines using bioinformatics analysis and RT-CPR. Then, we preliminarily analyzed the mechanisms involved in overexpression of LINC01123 in EC, finding that STAT1 could bind directly to the LINC01123 promoter region and activate its transcription. Clinical research with 106 patients indicated that high expression of LINC01123 was associated with advanced clinical progression and poor clinical outcome of EC patients. Functionally, knockdown of LINC01123 suppressed the proliferation, migration and invasion of EC cells, and promoted apoptosis. Mechanistically, we observed that LINC01123 may act as an endogenous sponge by competing for miR-516b, thereby regulating KIF4A. Overall, our study revealed a novel LINC01123/miR-516b/KIF4A pathway regulatory axis in EC pathogenesis. LINC01123 may be a novel prognostic biomarker and therapeutic target in EC.Abbreviations: EC: Endometrial cancer; LncRNA: Long non-coding RNA; EMT: epithelial-mesenchymal transition; miRNA: microRNA; qRT-PCR: Quantitative real-time polymerase chain reaction; SPSS: Statistical Package for Social Sciences; Chip: chromatin-immunoprecipitation, TCGA: The Cancer Genome Atlas; CCK-8: Cell Counting Kit-8; KIF4A: Chromosome-associated kinesin KIF4A.

Keywords: KIF4A; LncRNA LINC01123; biomarker; endometrial cancer; metastasis; miR-516b.