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分泌型 miR-153 控制高 Gleason 评分前列腺癌的增殖和侵袭。

Secreted miR-153 Controls Proliferation and Invasion of Higher Gleason Score Prostate Cancer.

机构信息

Institute of Bioimaging and Molecular Physiology (IBFM)-CNR, 20090 Segrate, Italy.

Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20054 Milan, Italy.

出版信息

Int J Mol Sci. 2022 Jun 6;23(11):6339. doi: 10.3390/ijms23116339.

Abstract

Prostate cancer (PC) is a male common neoplasm and is the second leading cause of cancer death in American men. PC is traditionally diagnosed by the evaluation of prostate secreted antigen (PSA) in the blood. Due to the high levels of false positives, digital rectal examination and transrectal ultrasound guided biopsy are necessary in uncertain cases with elevated PSA levels. Nevertheless, the high mortality rate suggests that new PC biomarkers are urgently needed to help clinical diagnosis. In a previous study, we have identified a network of genes, altered in high Gleason Score (GS) PC (GS ≥ 7), being regulated by miR-153. Until now, no publication has explained the mechanism of action of miR-153 in PC. By in vitro studies, we found that the overexpression of miR-153 in high GS cell lines is required to control cell proliferation, migration and invasion rates, targeting Kruppel-like factor 5 (). Moreover, miR-153 could be secreted by exosomes and microvesicles in the microenvironment and, once entered into the surrounding tissue, could influence cellular growth. Being upregulated in high GS human PC, miR-153 could be proposed as a circulating biomarker for PC diagnosis.

摘要

前列腺癌(PC)是一种男性常见的肿瘤,是美国男性癌症死亡的第二大主要原因。PC 传统上通过评估血液中的前列腺特异性抗原(PSA)来诊断。由于假阳性率高,对于 PSA 水平升高但不确定的病例,需要进行数字直肠检查和经直肠超声引导活检。然而,高死亡率表明迫切需要新的 PC 生物标志物来帮助临床诊断。在之前的一项研究中,我们已经确定了一个由受 miR-153 调控的基因组成的网络,这些基因在高 Gleason 评分(GS)PC(GS≥7)中发生改变。到目前为止,还没有文献解释 miR-153 在 PC 中的作用机制。通过体外研究,我们发现高 GS 细胞系中 miR-153 的过表达是控制细胞增殖、迁移和侵袭率所必需的,其靶向调节因子 5()。此外,miR-153 可以在细胞外体和微泡中由微环境分泌,一旦进入周围组织,就可以影响细胞生长。miR-153 在高 GS 人 PC 中上调,可作为 PC 诊断的循环生物标志物。

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