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LBX2-AS1 is activated by ZEB1 and promotes the development of esophageal squamous cell carcinoma by interacting with HNRNPC to enhance the stability of ZEB1 and ZEB2 mRNAs

Zhang, Yanshan, Chen, Weizuo, Pan, Tingting, Wang, Huijuan, Zhang, Yinguo, Li, Chao
Biochemical and biophysical research communications 2019 v.511 no.3 pp. 566-572
RNA-binding proteins, antisense RNA, cell movement, epithelium, messenger RNA, metastasis, non-coding RNA, ribonucleoproteins, squamous cell carcinoma, transcription factors, zinc finger motif
Long non-coding RNAs (lncRNAs) are a group of transcripts, which can regulate the progression of esophageal squamous cell carcinoma (ESCC). According to the data of TCGA, Ladybird homeobox 2 antisense RNA 1 (LBX2-AS1) is a highly expressed lncRNA in ESCC samples. Herein, we chose it for further study. Furtherly, dysregulation of LBX2-AS1 was identified in ESCC tissues with metastasis. Loss-of function assays were conducted and revealed that LBX2-AS1 knockdown suppressed ESCC cell migration and epithelial-mesenchymal transition (EMT). Zinc finger E-box binding homeobox 1 (ZEB1) and zinc finger E-box binding homeobox 2 (ZEB2) are two EMT-related transcription factors. Since LBX2-AS1 promoted the EMT progress and simultaneously enhanced the level of ZEB1 and ZEB2, we further investigated whether LBX2-AS1 promoted cell migration and EMT in ESCC by regulating ZEB1 and ZEB2. Mechanism investigations revealed that RNA binding protein heterogeneous nuclear ribonucleoprotein C (HNRNPC) could interact with LBX2-AS1, ZEB1 and ZEB2, simultaneously. The similar function of HNRNPC in regulating migration and EMT process was demonstrated. ZEB1 has been reported as a positive transcriptional regulator of lncRNA. Therefore, further mechanism analysis was made to demonstrate whether ZEB1 could regulate the transcription of LBX2-AS1. Collectively, our data showed that ZEB1-induced upregulation of LBX2-AS1 promoted cell migration and EMT process in ESCC via enhancing the stability of ZEB1 and ZEB2.