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MEIS2 通过下调 IL10 抑制乳腺癌的发展。

MEIS2 suppresses breast cancer development by downregulating IL10.

机构信息

Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Xiangya International Medical Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Cancer Rep (Hoboken). 2024 May;7(5):e2064. doi: 10.1002/cnr2.2064.

Abstract

BACKGROUND

Breast cancer (BC) is the most commonly diagnosed female cancer. Homeobox protein MEIS2, a key transcription factor, is involved in the regulation of many developmental and cellular processes. However, the role of MEIS2 in the development of breast cancer is still unclear.

AIMS

We aimed to examine the role of myeloid ecotropic insertion site (MEIS2) in breast cancer and the association of MEIS2 with breast cancer clinical stages and pathological grades. We revealed the underlying mechanism by which MEIS2 affected breast cancer cell growth and tumor development.

METHODS AND RESULTS

Using human BC cell lines, clinical samples and animal xenograft model, we reveal that MEIS2 functions as a tumor suppressor in breast cancer. The expression of MEIS2 is inversely correlated with BC clinical stages and pathological grades. MEIS2 knockdown (MEIS2-KD) promotes while MEIS2 overexpression suppresses breast cancer cell proliferation and tumor development in vitro and in animal xenograft models, respectively. To determine the biological function of MEIS2, we screen the expression of a group of MEIS2 potential targeting genes in stable-established cell lines. Results show that the knockdown of MEIS2 in breast cancer cells up-regulates the IL10 expression, but MEIS2 overexpression opposed the effect on IL10 expression. Furthermore, the suppressive role of MEIS2 in breast cancer cell proliferation is associated with the IL10 expression and myeloid cells infiltration.

CONCLUSION

Our study demonstrates that the tumor suppressor of MEIS2 in breast cancer progression is partially via down regulating the expression of IL10 and promoting myeloid cells infiltration. Targeting MEIS2 would be a potentially therapeutic avenue for BC.

摘要

背景

乳腺癌(BC)是最常见的女性癌症。同源盒蛋白 MEIS2 是一种关键的转录因子,参与调节许多发育和细胞过程。然而,MEIS2 在乳腺癌发展中的作用尚不清楚。

目的

我们旨在研究 MEIS2 在乳腺癌中的作用以及 MEIS2 与乳腺癌临床分期和病理分级的关系。我们揭示了 MEIS2 影响乳腺癌细胞生长和肿瘤发展的潜在机制。

方法和结果

使用人乳腺癌细胞系、临床样本和动物异种移植模型,我们揭示 MEIS2 在乳腺癌中起肿瘤抑制因子的作用。MEIS2 的表达与 BC 临床分期和病理分级呈负相关。MEIS2 敲低(MEIS2-KD)促进,而 MEIS2 过表达分别抑制体外和动物异种移植模型中的乳腺癌细胞增殖和肿瘤发展。为了确定 MEIS2 的生物学功能,我们在稳定建立的细胞系中筛选了一组 MEIS2 潜在靶向基因的表达。结果表明,乳腺癌细胞中 MEIS2 的敲低上调了 IL10 的表达,但 MEIS2 过表达则相反。此外,MEIS2 在乳腺癌细胞增殖中的抑制作用与 IL10 的表达和髓样细胞浸润有关。

结论

我们的研究表明,MEIS2 在乳腺癌进展中的肿瘤抑制作用部分是通过下调 IL10 的表达和促进髓样细胞浸润来实现的。靶向 MEIS2 可能是治疗乳腺癌的一种潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b8b/11074520/8806d9304df9/CNR2-7-e2064-g003.jpg

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