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长非编码 RNA TMEM147 反义 RNA 1/微小 RNA-124/信号转导和转录激活因子 3 轴在雌激素受体阳性乳腺癌中的作用。

Long non-coding RNA TMEM147 antisense RNA 1/microRNA-124/signal transducer and activator of transcription 3 axis in estrogen receptor-positive breast cancer.

机构信息

Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Department of PETCT Center, Cancer Hospital of Jiangsu Province, Nanjing, China.

出版信息

J Obstet Gynaecol Res. 2024 Sep;50(9):1604-1613. doi: 10.1111/jog.16037. Epub 2024 Aug 7.

Abstract

OBJECTIVE

This research aimed to probe the expression of long noncoding RNA TMEM147 antisense RNA 1 (TMEM147-AS1)/micro-RNA (miR)-124/signal transducer and activator of transcription 3 (STAT3) axis in estrogen receptor (ER)-positive breast cancer (BC).

METHODS

Sixty ER-positive BC patients undergoing surgical treatment were gathered. TMEM147-AS1, miR-124, and STAT3 expression levels in BC cells and tissues were measured. The binding sites of TMEM147-AS1 and miR-124, miR-124, and STAT3 were analyzed and validated. The miR-124, STAT3 overexpression (oe) sequences, TMEM147-AS1 oe, and interference sequences and their control sequences were planned and cells were transfected to assess their functions in BC cells biological functions.

RESULTS

TMEM147-AS1, as well as STAT3 was extremely expressed and miR-124 was lowly expressed in BC cells and tissues. Interference with TMEM147-AS1 restrained ER-positive BC cell malignant activities. Mechanistically, TMEM147-AS1 could competitively bind miR-124 in refraining miR-124 expression, and STAT3 was a target gene of miR-124. Oe of miR-124 effectively reversed the enhancement of BC cell proliferation and invasion induced by TMEM147-AS1 upregulation. Oe of STAT3 could reverse the inhibitory effect of miR-124 on BC cell malignant behaviors.

CONCLUSION

TMEM147-AS1 has oncogenic activity in ER-positive BC, which may be a result of the altered miR-124/STAT3 axis. Therefore, targeting the TMEM147-AS1/miR-124/STAT3 axis may be a target for ER-positive BC therapy.

摘要

目的

本研究旨在探讨长链非编码 RNA TMEM147 反义 RNA 1(TMEM147-AS1)/微小 RNA(miR)-124/信号转导和转录激活因子 3(STAT3)轴在雌激素受体(ER)阳性乳腺癌(BC)中的表达。

方法

收集 60 例接受手术治疗的 ER 阳性 BC 患者。测量 BC 细胞和组织中 TMEM147-AS1、miR-124 和 STAT3 的表达水平。分析和验证 TMEM147-AS1 和 miR-124、miR-124 和 STAT3 的结合位点。设计并转染 miR-124、STAT3 过表达(oe)序列、TMEM147-AS1 oe 和干扰序列及其对照序列,以评估它们在 BC 细胞生物学功能中的作用。

结果

TMEM147-AS1 和 STAT3 在 BC 细胞和组织中表达极高,而 miR-124 表达水平较低。干扰 TMEM147-AS1 可抑制 ER 阳性 BC 细胞的恶性活性。机制上,TMEM147-AS1 可竞争性结合 miR-124 抑制 miR-124 表达,STAT3 是 miR-124 的靶基因。miR-124 的过表达可有效逆转 TMEM147-AS1 上调引起的 BC 细胞增殖和侵袭增强。STAT3 的过表达可逆转 miR-124 对 BC 细胞恶性行为的抑制作用。

结论

TMEM147-AS1 在 ER 阳性 BC 中具有致癌活性,这可能是由于改变了 miR-124/STAT3 轴。因此,靶向 TMEM147-AS1/miR-124/STAT3 轴可能是 ER 阳性 BC 治疗的靶点。

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