长链非编码 RNA SLCO4A1-AS1/miR-876-3p/RBBP6 轴通过 JNK 信号通路调节急性淋巴细胞白血病中的细胞增殖和凋亡。

The lncRNA SLCO4A1-AS1/miR-876-3p/RBBP6 axis regulates cell proliferation and apoptosis in acute lymphocytic leukemia via the JNK signaling pathway.

机构信息

Department of Hematology, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, China.

Department of Internal Medicine, The Second Children & Women's Healthcare of Jinan City, Jinan, China.

出版信息

Int J Lab Hematol. 2021 Oct;43(5):1050-1061. doi: 10.1111/ijlh.13501. Epub 2021 Mar 8.

DOI:10.1111/ijlh.13501

PMID:33683013

Abstract

INTRODUCTION

Acute lymphocytic leukemia (ALL) is a hematologic malignancy caused by the clonal proliferation of immature lymphocytes. Long noncoding RNAs (lncRNAs) have been reported as critical regulators in several cancers, including ALL. LncRNA SLCO4A1 antisense RNA 1 (SLCO4A1-AS1) has been revealed to be implicated in tumorigenesis of several cancers. Our study focused on the role of SLCO4A1-AS1 in ALL.

METHODS

RT-qPCR, Western blot analysis, CCK-8, EdU, and Flow cytometry analysis were used to explore the biological function of SLCO4A1-AS1 in ALL cellular processes. Luciferase reporter and RNA pull-down assays were applied to explore the mechanism of SLCO4A1-AS1 in ALL cells.

RESULTS

SLCO4A1-AS1 was upregulated in ALL tissues and cell lines. We found that suppression of SLCO4A1-AS1 suppressed ALL cell proliferation and facilitated cell apoptosis. Our result confirmed that SLCO4A1-AS1 acted as a ceRNA by sponging microRNA 876-3p (miR-876-3p) to upregulate retinoblastoma binding protein 6 (RBBP6) expression in ALL cells. Moreover, SLCO4A1-AS1 activated the JNK signaling pathway by upregulating RBBP6. Rescue assays revealed that the activation of the JNK signaling or overexpression of RBBP6 revered the suppressive effect of SLCO4A1-AS1 knockdown on growth of ALL cells.

CONCLUSION

SLCO4A1-AS1 promoted cell growth of ALL by the miR-876-3p/RBBP6 axis to activate the JNK signaling pathway.

摘要

简介

急性淋巴细胞白血病（ALL）是一种由不成熟淋巴细胞克隆性增殖引起的血液系统恶性肿瘤。长链非编码 RNA（lncRNA）已被报道为多种癌症（包括 ALL）中的关键调控因子。LncRNA SLCO4A1 反义 RNA 1（SLCO4A1-AS1）已被揭示与几种癌症的发生有关。我们的研究集中在 SLCO4A1-AS1 在 ALL 中的作用。

方法

使用 RT-qPCR、Western blot 分析、CCK-8、EdU 和流式细胞术分析来研究 SLCO4A1-AS1 在 ALL 细胞过程中的生物学功能。使用荧光素酶报告和 RNA 下拉实验来研究 SLCO4A1-AS1 在 ALL 细胞中的作用机制。

结果

SLCO4A1-AS1 在 ALL 组织和细胞系中上调。我们发现抑制 SLCO4A1-AS1 抑制 ALL 细胞增殖并促进细胞凋亡。我们的结果证实，SLCO4A1-AS1 通过海绵 microRNA 876-3p（miR-876-3p）来上调视网膜母细胞瘤结合蛋白 6（RBBP6）的表达，从而作为 ceRNA 在 ALL 细胞中发挥作用。此外，SLCO4A1-AS1 通过上调 RBBP6 激活 JNK 信号通路。挽救实验表明，JNK 信号的激活或 RBBP6 的过表达逆转了 SLCO4A1-AS1 敲低对 ALL 细胞生长的抑制作用。