Work

Long noncoding RNA HNF1A-AS1 promotes ovarian cancer growth and M2 macrophage polarization by counteracting miR-214-mediated suppression of semaphorin 4D signaling

Year: 2025

Type: article

Abstract: To determine whether lncRNA HNF1A-AS1 affects EOC growth and macrophage polarization through miR-214/SEMA4D. The endogenous HNF1A-AS1 and miR-214 levels in human EOC cell lines were compared with those in normal ovarian epithelial IOSE80 cells. HNF1A-AS1 was overexpressed or silenced to investigate whether HNF1A-AS1 regulates miR-214/SEMA4D in SKOV3 cells and xenograft tumors, as well as the phenotypic switching of THP-1 cells. Compared with IOSE80 cells, EOC cells present significantly higher HNF1A-AS1 levels and lower miR-214 levels. Fluorescence in situ hybridization revealed predominant cytoplasmic localization of HNF1A-AS1, supporting its role as a competing endogenous RNA. HNF1A-AS1 and miR-214 antagonized each other in SKOV3 cells. In vitro, HNF1A-AS1 inhibited SKOV3 apoptosis and promoted migration and invasion. HNF1A-AS1 overexpression enhanced miR-214 downstream of SEMA4D/PLEXIN-B1/TIAM1/RAC signaling, but miR-214 mimics significantly reversed this effect. Compared with control tumors, xenograft tumors derived from HNF1A-AS1-overexpressing SKOV3 cells present increased tumor growth, attenuated miR-214 expression, and activated SEMA4D/PLEXIN-B1/TIAM/RAC signaling. The knockdown of HNF1A-AS1 had opposite effects. Additionally, HNF1A-AS1 promoted M2 phenotypic switching in THP-1 cells, which could be reversed by miR-214 overexpression or SEMA4D silencing. Our study suggests that by antagonizing miR-214, HNF1A-AS1 activates the SEMA4D/PLEXIN-B1/TIAM/RAC pathway, facilitating EOC growth and potentially promoting M2 macrophage polarization in the TME. HNF1A-AS1 represents a compelling therapeutic target for treating EOC.

Source: Acta Biochimica et Biophysica Sinica

DOI: 10.3724/abbs.2025208

Authors: Yang Liu, Yanzhi Wu, Yujie Gengxiao, Yan Li, Jiamei Song, Chunyi Sun

Institutions: Kunming Medical University, Second Affiliated Hospital of Kunming Medical College

Language: English

Topic: Cancer-related molecular mechanisms research

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: Kunming Medical University