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长链非编码 RNA TSLNC8 通过 miR-214-3p/FOXP2 轴抑制乳腺癌细胞的增殖。

LncRNA TSLNC8 inhibits proliferation of breast cancer cell through the miR-214-3p/FOXP2 axis.

机构信息

Department of Breast and Thyroid Surgery, Weihai Municipal Hospital, Weihai, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8440-8448. doi: 10.26355/eurrev_201910_19156.

Abstract

OBJECTIVE

In multiple cancers, heterozygosity is frequently lost for the tumor-suppressive long noncoding RNA (lncRNA). The expression, function, and molecular mechanisms of tumor suppressive lncRNA on chromosome 8p12 (TSLNC8) in breast cancer are still unknown.

MATERIALS AND METHODS

QRT-PCR assays were carried out to evaluate the level of TSLNC8 in breast cancer tissues and cell lines. MTT, colony formation, and anchorage-independent growth assays were performed to investigate the effect of TSLNC8 on cell proliferation, and flow cytometry assays were conducted to detect cell percent of different phases. Luciferase reporter assays were used to confirm the interaction of different molecules.

RESULTS

TSLNC8 is significantly increased in breast cancer tissues and cell lines. Up-regulation of TSLNC8 reduces the proliferation capacity of breast cancer cells and the transition from G1 to S phase of the cell cycle. Further analysis indicated that TSLNC8 could directly bind to miR-214-3p. Up-regulation of miR-214-3p may attenuate the suppressive role of TSLNC8 on the proliferation capacity of breast cancer cells. Moreover, miR-214-3p was found to directly interact with the 3'-untranslated region (UTR) of Forkhead box P2 (FOXP2) in luciferase assays, suggesting that FOXP2 may be one of the downstream targets of miR-412-3p.

CONCLUSIONS

TSLNC8 was found to inhibit the proliferation and G1/S phase transition of breast cancer cells, an effect mediated by miR-214-3p/FOXP2 axis. Our study provides evidence that TSLNC8 may act as a suppressive lncRNA and represent a novel therapeutic target for breast cancer therapy.

摘要

目的

在多种癌症中,肿瘤抑制性长非编码 RNA(lncRNA)的杂合性经常丢失。乳腺癌 8p12 染色体上的肿瘤抑制性长非编码 RNA(TSLNC8)的表达、功能和分子机制尚不清楚。

材料和方法

采用 QRT-PCR 检测乳腺癌组织和细胞系中 TSLNC8 的水平。MTT、集落形成和无锚定独立生长实验检测 TSLNC8 对细胞增殖的影响,流式细胞术检测细胞各期比例。荧光素酶报告实验验证不同分子的相互作用。

结果

TSLNC8 在乳腺癌组织和细胞系中显著增加。上调 TSLNC8 降低乳腺癌细胞的增殖能力,并降低细胞周期从 G1 期到 S 期的转化。进一步分析表明,TSLNC8 可直接与 miR-214-3p 结合。miR-214-3p 的上调可能减弱 TSLNC8 对乳腺癌细胞增殖能力的抑制作用。此外,荧光素酶实验表明 miR-214-3p 可直接与叉头框 P2(FOXP2)的 3'非翻译区(UTR)相互作用,提示 FOXP2 可能是 miR-412-3p 的下游靶标之一。

结论

发现 TSLNC8 可抑制乳腺癌细胞的增殖和 G1/S 期转化,该作用由 miR-214-3p/FOXP2 轴介导。本研究为 TSLNC8 可能作为抑制性 lncRNA 并代表乳腺癌治疗的新治疗靶点提供了证据。

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