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Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein.

Authors :
Wang CL
Li JC
Zhou CX
Ma CN
Wang DF
Wo LL
He M
Yin Q
He JR
Zhao Q
Source :
Breast cancer research and treatment [Breast Cancer Res Treat] 2021 Oct; Vol. 189 (3), pp. 607-619. Date of Electronic Publication: 2021 Aug 09.
Publication Year :
2021

Abstract

Purpose: Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in cancer metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of an LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated.<br />Methods: RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling.<br />Results: We analyzed the RNA-seq data of MDA-MB-231 and its highly metastatic derivative MDA-MB-231-LM2 cell lines (referred to as LM2) and identified a novel lncRNA (NR_027263) named as ARHGAP5-AS1, which expression was significantly downregulated in LM2 cells. Further functional investigation showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7.<br />Conclusion: ARHGAP5-AS1 inhibits breast cancer cell migration via stabilization of SMAD7 protein and could serve as a novel biomarker and a potential target for breast cancer in the future.<br /> (© 2021. The Author(s).)

Details

Language :
English
ISSN :
1573-7217
Volume :
189
Issue :
3
Database :
MEDLINE
Journal :
Breast cancer research and treatment
Publication Type :
Academic Journal
Accession number :
34370213
Full Text :
https://doi.org/10.1007/s10549-021-06286-5