AUTHOR=Yang Xue , Qi Fei , Wei Shanchen , Lin Lianjun , Liu Xinmin 

TITLE=The Transcription Factor C/EBPβ Promotes HFL-1 Cell Migration, Proliferation, and Inflammation by Activating lncRNA HAS2-AS1 in Hypoxia

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.651913

DOI=10.3389/fcell.2021.651913

ISSN=2296-634X

ABSTRACT=Objective: Recent studies were widely concerned about the role of lncRNAs in hypoxic pulmonary hypertension (HPH). HAS2 was found significantly highly expressed in HPH, but the antisense of HAS2 (HAS2-AS1) has not been explored in HPH, providing a new potential therapeutic target of HPH. Methods: In this study, HFL-1 cells were cultured under hypoxia conditions to stimulate the pathological process of HPH. Transwell and wound healing assays were used to detect HFL-1 cell migration, and CCK 8 assay was used to detect cell proliferation. The upstream transcription factor of HAS2-AS1 was predicted by JASPAR website, and the binding site between C/EBP and HAS2-AS1 was predicted by JASPAR, too. In order to verify the association between C/EBP and the HAS2 promoter region, we used chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene detection, Western blot to detect the expression of inflammation-related proteins, and qRT-PCR to detect the expression of HAS2-AS1 and HAS2. Idiopathic pulmonary fibrosis (IPF) with HPH patient microarray data was downloaded from the GEO database and analyzed by R software. Results: Our study showed that HAS2-AS1 and C/EBP were highly expressed in hypoxic HFL-1 cells, and the knockdown of HAS2-AS1 expression could inhibit the proliferation, migration and inflammatory response of HFL-1 cells. C/EBP binds to the promoter region of HAS2-AS1 and has a positive regulation effect on the transcription of HAS2-AS1. Furthermore, C/EBP can regulate the proliferation, migration and inflammatory response of HFL-1 cells through HAS2-AS1. Conclusion: This study suggested that C/EBP could up-regulate HAS2-AS1 expression and induce HFL-1 cells proliferation, migration and inflammation response.