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Wnt-11和miR-21表达上调触发侵袭性前列腺癌细胞的上皮-间质转化

Upregulated Wnt-11 and miR-21 Expression Trigger Epithelial Mesenchymal Transition in Aggressive Prostate Cancer Cells.

作者信息

Arisan Elif Damla, Rencuzogullari Ozge, Freitas Ines Lua, Radzali Syanas, Keskin Buse, Kothari Archana, Warford Antony, Uysal-Onganer Pinar

机构信息

Institute of Biotechnology, Gebze Technical University, Gebze 41400, Kocaeli, Turkey.

Department of Molecular Biology and Genetics, Istanbul Kultur University, Atakoy Campus, 34156 Istanbul, Turkey.

出版信息

Biology (Basel). 2020 Mar 9;9(3):52. doi: 10.3390/biology9030052.

Abstract

Prostate cancer (PCa) is the second-leading cause of cancer-related death among men. microRNAs have been identified as having potential roles in tumorigenesis. An oncomir, miR-21, is commonly highly upregulated in many cancers, including PCa, and showed correlation with the Wnt-signaling axis to increase invasion. Wnt-11 is a developmentally regulated gene and has been found to be upregulated in PCa, but its mechanism is unknown. The present study aimed to investigate the roles of miR-21 and Wnt-11 in PCa in vivo and in vitro. First, different Gleason score PCa tissue samples were used; both miR-21 and Wnt-11 expressions correlate with high Gleason scores in PCa patient tissues. This data then was confirmed with formalin-fixed paraffin cell blocks using PCa cell lines LNCaP and PC3. Cell survival and colony formation studies proved that miR-21 involves in cells' behaviors, as well as the epithelial-mesenchymal transition. Consistent with the previous data, silencing miR-21 led to significant inhibition of cellular invasiveness. Overall, these results suggest that miR-21 plays a significant role related to Wnt-11 in the pathophysiology of PCa.

摘要

前列腺癌(PCa)是男性癌症相关死亡的第二大原因。微小RNA已被确定在肿瘤发生中具有潜在作用。一种致癌miRNA,即miR-21,在包括PCa在内的许多癌症中通常高度上调,并显示与Wnt信号轴相关以增加侵袭。Wnt-11是一个受发育调控的基因,已发现在PCa中上调,但其机制尚不清楚。本研究旨在探讨miR-21和Wnt-11在PCa体内和体外的作用。首先,使用不同Gleason评分的PCa组织样本;miR-21和Wnt-11的表达均与PCa患者组织中的高Gleason评分相关。然后使用PCa细胞系LNCaP和PC3的福尔马林固定石蜡细胞块对该数据进行了验证。细胞存活和集落形成研究证明,miR-21参与细胞行为以及上皮-间质转化。与先前的数据一致,沉默miR-21导致细胞侵袭性显著抑制。总体而言,这些结果表明miR-21在PCa的病理生理学中与Wnt-11相关发挥重要作用。

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