LncRNA APOC1P1-3 promoting anoikis-resistance of breast cancer cells

Qi Lu,Youping Jin,Xiuling Zhi,Xingjun Qin,Ping Zhou,Luying Li,Ping Zhu,Yabiao Gao,Xin Li,Li Wang,Xue Wang,Jerry Yu

doi:10.1186/s12935-021-01916-w

Abstract

BackgroundAnoikis resistance plays a critical role in the tumor metastasis by allowing survival of cancer cells in the systemic circulation. We previously showed that long non-coding RNAs APOC1P1-3 (lncRNA APOC1P1-3) inhibit apoptosis of breast cancer cells. In this study, we explored its role in anoikis resistance.MethodsWe induced anoikis resistance in two breast cancer cell lines (MCF-7 and MDA-MB-231) under anchorage-independent culture conditions and studied lncRNA APOC1P1-3 effects on apoptosis. Using Dual-Luciferase activity assay, we determined whether it specifically binds to miRNA-188-3P. We further explored its role in lung metastasis by injecting MDA-MB-231 and MDA-MB-231-APOC1P1-3-knock-down cells in female BALB/c nude mice.ResultsWe found that lncRNA APOC1P1-3 suppressed early apoptosis of these cells (demonstrated by gain or loss of their function, respectively) and promoted anoikis resistance via reducing activated- Caspase 3, 8, 9 and PARP. Moreover, it specifically binds to the target miRNA-188-3p acting as a “sponge” to block the inhibition of Bcl-2 (an anti-apoptosis protein).ConclusionsOur study supports a theory that lncRNA APOC1P1-3 can promote development of breast cancer metastasis via anoikis resistance by specifically binding to miRNA-188-3p to block the inhibition of Bcl-2.

Highlights

Breast cancer metastasis is a complicated multistep process involving cell detachment from the original site, survival in the circulatory and lymphatic systems, and colonization in distant target organs [1]
The expressions decreased in MCF-7a cells, which were overexpressed with pcDNA3.1-sense. These results indicate that upregulation of long noncoding RNAs (lncRNAs) APOC1P1-3 could influence anoikis resistance via caspase-dependent pathway
The cross‐talking between miRNA‐188‐3p and lncRNA‐APOC1P1‐3 We further explored the effect of miRNA-188-3p on anoikis resistance. miRNA-188-3p was first overexpressed in MDA-MB-231a cells by transfection with miRNA-188-3p mimics

Summary

Introduction

Breast cancer metastasis is a complicated multistep process involving cell detachment from the original site, survival in the circulatory and lymphatic systems, and colonization in distant target organs [1]. Anoikis is a particular type of apoptosis of epithelial and endothelial cells on losing attachment from the appropriate extracellular matrix or neighboring cells LncRNAs are a set of key regulatory RNAs with transcripts longer than 200 nucleotides They are involved in almost all physiological and pathological processes, including cell proliferation, apoptosis, stem. LncRNA MALAT1 was discovered first in non-small cell lung cancer patients with high metastasis and poor prognosis [13] It is upregulated in prostate, colorectal, and bladder cancers [14,15,16]. We sought out long intergenic non-coding RNA APOC1P1-3 from breast cancer tissues and cell lines It was upregulated in most cases and correlated with tumor size and hypomethylation in its promoter region. We explored its role in anoikis resistance

Methods

Results

Conclusion