Knockdown of NAA25 Suppresses Breast Cancer Progression by Regulating Apoptosis and Cell Cycle.

Jingkai Xu,Guozheng Li,Bo Zhang,Xianbo Zuo,Yong Cui,Xuejun Zhang,Zhi Li

doi:10.3389/fonc.2021.755267

Abstract

NAA25 gene variants were reported as risk factors for type 1 diabetes, rheumatoid arthritis and acute arterial stroke. But it’s unknown whether it could contribute to breast cancer. We identified rs11066150 in lncHSAT164, which contributes to breast cancer, in our earlier genome-wide long non-coding RNA association study on Han Chinese women. However, rs11066150 A/G variant is also located in NAA25 intron. Based on the public database, such as TCGA and Curtis dataset, NAA25 gene is highly expressed in breast cancer tissues and this result has also been proved in our samples and cell lines through RT-qPCR and western blot analysis. To better understand the function of NAA25 in breast cancer, we knocked down the expression of NAA25 in breast cancer cell lines, FACS was used to detect cell apoptosis and cell cycle and colony formation assay was used to detect cell proliferation. We found that NAA25-deficient cells could increase cell apoptosis, delay G2/M phase cell and decrease cell clone formation. RNA sequencing was then applied to analyze the molecular profiles of NAA25−deficient cells, and compared to the control group, NAA25 knockdown could activate apoptosis-related pathways, reduce the activation of tumor-associated signaling pathways and decrease immune response-associated pathways. Additionally, RT-qPCR was employed to validate these results. Taken together, our results revealed that NAA25 was highly expressed in breast cancer, and NAA25 knockdown might serve as a therapeutic target in breast cancer.

Highlights

Breast cancer is the most common and a leading cause of cancer-related deaths of women worldwide [1]
gene ontology (GO) term analysis was performed to N-alpha-acetyltransferase 25 (NAA25)-deficient cells, and the results showed that many genes were associated with infection and immunity (Figure 3D and Supplementary Figure 2D)
We reported rs11066150 as an intron variant SNP in NAA25 gene

Summary

INTRODUCTION

Breast cancer is the most common and a leading cause of cancer-related deaths of women worldwide [1]. The relationship between NAA25 and breast cancer is still unknown. NAA25 encodes the auxiliary subunit, which could affect posttranslational modifications by forming N-terminal acetyltransferase B complex with catalytic subunit NAA20 [11]. In yeast, it can regulate actin remodeling, and stabilize actin cytoskeleton and mitochondrial targeting [12, 13]. We tested NAA25 gene expression in breast cancer tissues, para-carcinoma tissues, breast cancer cell lines and normal breast epithelial cell lines. We knocked down NAA25 gene expression in breast cancer cells and explored its influence on tumor cell proliferation, apoptosis and cell cycle. RNA-seq analysis was used to clarify the molecular profiles of NAA25-deficient cells

MATERIALS AND METHODS

RESULTS

DISCUSSION

Findings

ETHICS STATEMENT