目的:本研究旨在探讨长链非编码RNATMEM147反义RNA1(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。分析并验证了TMEM147-AS1和miR-124、miR-124和STAT3的结合位点。miR-124,STAT3过表达(oe)序列,TMEM147-AS1oe,计划干扰序列及其控制序列,并转染细胞以评估其在BC细胞生物学功能中的功能。
结果:TMEM147-AS1和STAT3在BC细胞和组织中极端表达,miR-124低表达。干扰TMEM147-AS1可抑制ER阳性BC细胞的恶性活性。机械上,TMEM147-AS1可以竞争性结合miR-124抑制miR-124表达,STAT3是miR-124的靶基因。miR-124的Oe有效逆转了TMEM147-AS1上调诱导的BC细胞增殖和侵袭的增强。STAT3的Oe可以逆转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miR-124/STAT3轴改变的结果。因此,靶向TMEM147-AS1/miR-124/STAT3轴可能是ER阳性BC治疗的靶标.
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.
CONCLUSIONS: 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.