长链非编码 RNA BRE-AS1 通过下调 miR-21 抑制三阴性乳腺癌中癌细胞的增殖、迁移和侵袭，并预测患者的生存。

Long non-coding RNA BRE-AS1 inhibits the proliferation, migration, and invasion of cancer cells in triple-negative breast cancer and predicts patients' survival by downregulating miR-21.

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei Province, 075000, People's Republic of China.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei Province, 075000, People's Republic of China.

出版信息

BMC Cancer. 2021 Jun 28;21(1):745. doi: 10.1186/s12885-021-08294-6.

BACKGROUND

BRE-AS1 is a recently identified tumor suppressor in non-small cell lung cancer. It role in other human diseases remains elusive.

METHODS

Differential expression of BRE-AS1 in with triple-negative breast cancer (TNBC) patients (n = 74, patient group) and healthy volunteers (n = 58, control group) was studied with RT-qPCR. The direct interaction between BRE-AS1 and premature microRNA-21 (miR-21) was assessed by RNA pull-down assay. The interactions among BRE-AS1, miR-21 and PTEN were evaluated by overexpression assays. CCK-8 assay and Transwell assay were used to evaluate cell behaviors.

RESULTS

BRE-AS1 was downregulated in TNBC, while miR-21 was highly expressed in TNBC. Low expression levels of lncRNA BRE-AS1 and high expression levels of miR-21 were significantly correlated with unfavorable survival outcomes. BRE-AS1 and miRNA-21 were inversely correlated across TNBC samples, not control samples. BRE-AS1 decreased miR-21 expression and increased PTEN expression while miR-21showed no role in BRE-AS1 expression. RNA pull-down assay illustrated that BRE-AS1 may sponge premature miR-21 to suppress it maturation. Overexpression of BRE-AS1 decreased cell behaviors, while overexpression of miR-21 promoted cell behaviors. MiR-21 suppressed the role of BRE-AS1 in cancer cell behaviors.

CONCLUSION

Therefore, BRE-AS1 may inhibit TNBC by downregulating miR-21.

背景

BRE-AS1 是一种最近在非小细胞肺癌中被鉴定的肿瘤抑制因子。它在其他人类疾病中的作用仍不清楚。

方法

采用 RT-qPCR 研究了三阴性乳腺癌（TNBC）患者（n=74，患者组）和健康志愿者（n=58，对照组）中 BRE-AS1 的差异表达。采用 RNA 下拉实验评估 BRE-AS1 与早期 microRNA-21（miR-21）之间的直接相互作用。通过过表达实验评估 BRE-AS1、miR-21 和 PTEN 之间的相互作用。CCK-8 检测和 Transwell 检测用于评估细胞行为。

结果

在 TNBC 中，BRE-AS1 下调，而 miR-21 在 TNBC 中高度表达。lncRNA BRE-AS1 表达水平低和 miR-21 表达水平高与不良生存结果显著相关。在 TNBC 样本中，而不是对照样本中，低表达水平的 lncRNA BRE-AS1 和高表达水平的 miR-21 呈负相关。BRE-AS1 降低 miR-21 的表达并增加 PTEN 的表达，而 miR-21 对 BRE-AS1 的表达没有作用。RNA 下拉实验表明，BRE-AS1 可能通过海绵吸附早期的 miR-21 来抑制其成熟。BRE-AS1 的过表达降低了细胞行为，而过表达 miR-21 则促进了细胞行为。miR-21 抑制了 BRE-AS1 在癌细胞行为中的作用。