Ephrin Type-A Receptor 2-antisense RNA1/2 Promote Proliferation and Migration of MDA-MB-231 Cells Through -dependent Ras Signaling Pathway Mediated by MAPK8/JNK1, MAPK9/JNK2-NFATC2/NFAT1 and JUND

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2024 Jun 10

PMID 38855323

Authors

Tokifumi Odaka

Ryou Sakamoto

Kazuhiro Kumagai

Kazu Okuma

Mikio Nishizawa

Tominori Kimura

Affiliations

Soon will be listed here.

Abstract

Ephrin type-A receptor 2 (EPHA2) is a receptor tyrosine kinase that is overexpressed in a variety of cancers, including breast cancer. EPHA2 expression may be causally related to tumorigenesis; therefore, it is important to understand how expression is regulated. We previously reported that EPHA2 antisense RNA (EPHA2-AS), a natural antisense transcript, is an important modulator of EPHA2 mRNA levels and hence production of EPHA2 protein. EPHA2-AS encodes two splice variants, EPHA2-AS1 and EPHA2-AS2. The two variants are constitutively expressed in a concordant manner with EPHA2 mRNA in human breast adenocarcinoma cell lines and in patient samples, with the highest levels detected in the basal-like/triple-negative molecular subtype of breast cancer cells. In this study, we investigated the mechanism of EPHA2-AS1/2 in triple-negative breast cancer using MDA-MB-231 cells. We performed RNA-seq transcriptome analyses of MDA-MB-231 cells treated with AHCC, which suppressed expression of EPHA2-AS1/2 and EPHA2 mRNA, and EPHA2-AS1/2-silenced MDA-MB-231 cells. Bioinformatics analyses identified 545 overlapping differentially expressed genes that were significantly up- or down-regulated by these treatments. Subsequent functional enrichment analyses of the overlapping genes in combination with assays indicated that EPHA2-AS1/2 may promote the proliferation and migration of MDA-MB-231 cells through the -dependent Ras signaling pathways mediated by MAPK8/JNK1, MAPK9/JNK2-NFATC2/NFAT1 (proliferation and migration) and JUND (migration). These results thus suggest that EPHA2-AS1/2 may represent a potential molecular target for triple-negative breast cancer treatment.

Citing Articles

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