miRNA-激肽酶相互作用：癌症表观遗传调控的镶嵌体。

The miRNA-kallikrein interaction: a mosaic of epigenetic regulation in cancer.

机构信息

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.

Department of Laboratory Medicine, and the Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.

出版信息

Biol Chem. 2018 Sep 25;399(9):973-982. doi: 10.1515/hsz-2018-0112.

DOI:10.1515/hsz-2018-0112

PMID:29604203

Abstract

The kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases with trypsin- and chymotrypsin-like activities. Dysregulated expression and/or aberrant activation of KLKs has been linked to various pathophysiological processes, including cancer. Many KLKs have been identified as potential cancer biomarkers. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by pairing to the 3' untranslated region (UTR) of complimentary mRNA targets. miRNAs are dysregulated in many cancers, including prostate, kidney and ovarian cancers. Several studies have shown that miRNAs are involved in the post-transcriptional regulation of KLKs. However, recent evidence suggests that miRNAs can also act as downstream effectors of KLKs. In this review, we provide an update on the epigenetic regulation of KLKs by miRNAs. We also present recent experimental evidence that supports the regulatory role of KLKs on miRNA networks. The potential diagnostic and therapeutic applications of miRNA-kallikrein interactions are also discussed.

摘要

激肽释放酶相关肽酶（KLKs）构成了一个具有胰蛋白酶和糜蛋白酶样活性的 15 种高度保守丝氨酸蛋白酶家族。KLKs 的表达失调和/或异常激活与包括癌症在内的各种病理生理过程有关。许多 KLKs 已被确定为潜在的癌症生物标志物。 microRNAs（miRNAs）是一类小的非编码 RNA，通过与互补 mRNA 靶标的 3'非翻译区（UTR）配对来调节基因表达。miRNAs 在许多癌症中失调，包括前列腺癌、肾癌和卵巢癌。几项研究表明，miRNAs 参与 KLKs 的转录后调控。然而，最近的证据表明，miRNAs 也可以作为 KLKs 的下游效应子。在这篇综述中，我们提供了 miRNAs 对 KLKs 的表观遗传调控的最新更新。我们还介绍了最近支持 KLKs 对 miRNA 网络的调节作用的实验证据。还讨论了 miRNA-激肽释放酶相互作用的潜在诊断和治疗应用。