Piperigkou Zoi, Franchi Marco, Riethmüller Christoph, Götte Martin, Karamanos Nikos K
Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
Department of Gynecology and Obstetrics, Münster University Hospital, Münster, Germany.
Matrix Biol Plus. 2020 Jan 22;6-7:100024. doi: 10.1016/j.mbplus.2020.100024. eCollection 2020 May.
Secreted microRNAs (miRNAs) reside in a complex regulatory network with extracellular matrix (ECM) macromolecules, which affect cell-cell communication, therefore miRNA expression highlights its significance in several aspects of human diseases, including cancer. miRNA-mediated regulation of breast cancer has received considerable attention due to evidence that shows miRNAs to mediate estrogen receptor (ER) status, metastasis, chemoresistance and epithelial-to-mesenchymal transition (EMT). miR-200b is a pluripotent miRNA, which is inversely regulated by ERα and ERβ in mammary cancer. It has been identified as tumor suppressor and EMT inhibitor serving as a critical biomarker, as its expression in breast tumor determines the disease-free survival, thus highlighting its roles in breast cancer invasion and metastasis. The main goal of this study was to investigate the role of miR-200b in modulating the behavior of breast cancer cells with different ER status. We demonstrate that estrogen signaling through ERs reduces miR-200b expression levels in ERα-positive breast cancer cells. Moreover, miR-200b upregulation reduces the aggressive phenotype of ERβ-positive breast cancer cells by inhibiting cell invasiveness and motility, followed by ECM reorganization as well as cytoskeletal and morphological changes concluded from deep inspection of cell topography. Future investigation towards the mechanistic perspective of miR-200b effects in the behavior of aggressive mammary cancer cells appears rewarding in order to expand our understanding of miR-200b as a novel mediator beyond breast cancer diagnosis and pharmaceutical targeting.
分泌型微小RNA（miRNA）存在于与细胞外基质（ECM）大分子构成的复杂调控网络中，这一网络影响细胞间通讯，因此miRNA表达在包括癌症在内的人类疾病的多个方面都凸显出其重要性。由于有证据表明miRNA介导雌激素受体（ER）状态、转移、化疗耐药性及上皮-间质转化（EMT），miRNA介导的乳腺癌调控受到了相当多的关注。miR-200b是一种多能miRNA，在乳腺癌中受ERα和ERβ的反向调控。它已被确定为肿瘤抑制因子和EMT抑制剂，是一种关键的生物标志物，因为其在乳腺肿瘤中的表达决定了无病生存期，从而凸显了其在乳腺癌侵袭和转移中的作用。本研究的主要目的是探讨miR-200b在调节不同ER状态的乳腺癌细胞行为中的作用。我们证明，通过ERs的雌激素信号传导降低了ERα阳性乳腺癌细胞中miR-200b的表达水平。此外，miR-200b的上调通过抑制细胞侵袭性和运动性降低了ERβ阳性乳腺癌细胞的侵袭性表型，随后通过对细胞拓扑结构的深入检查得出细胞外基质重组以及细胞骨架和形态变化。为了扩展我们对miR-200b作为一种超越乳腺癌诊断和药物靶向的新型介质的理解，从miR-200b对侵袭性乳腺癌细胞行为影响的机制角度进行进一步研究似乎很有意义。
