Crosstalk between microRNA30a/b/c/d/e-5p and the canonical Wnt pathway: implications for multiple myeloma therapy.
Crosstalk between microRNA30a/b/c/d/e-5p and the canonical Wnt pathway: implications for multiple myeloma therapy.
复制标题
DOI：
10.1158/0008-5472.can-14-0994
复制
发表时间：
2014-10-01
期刊：
影响因子：
11.2
通讯作者：
Carrasco RD
中科院分区：
文献类型：
--
作者：
Zhao JJ;Carrasco RD
通过Wnt/β-catenin信号通路的转录失调是多种常见人类癌症发病机制的基础。这些包括上皮癌，如结肠直肠癌（CC）和血液学恶性肿瘤，如多发性骨髓瘤（MM）。因此，Wnt/β-catenin通路可能为癌症治疗提供一个有吸引力的靶点。然而，这种方法迄今为止被证明具有挑战性，因为该途径在生理稳态中起着许多关键作用，并且因为广泛靶向该途径的药物具有不可接受的副作用。MicroRNAs （miRs）作为基因表达的调节因子，也与MM和其他人类癌症的发病机制有关，如果它们能在体内有效应用，将为新的治疗方法提供希望。由于BCL9是β-catenin的关键转录共激活因子，在许多人类癌症中异常表达，但在正常组织中含量低，因此Wnt/β-catenin/BCL9复合物已成为Wnt/β-catenin活性失调的癌症中有希望且最可能相对安全的治疗靶点。本文综述了Wnt抑制剂生物学的最新进展，以及BCL9与microRNA-30a/b/c/d/e-5p之间可能存在的用于MM治疗的功能联系。
Dysregulation of transcription via the Wnt/β-catenin signaling pathway underlies the pathogenesis of a wide variety of frequent human cancers. These include epithelial carcinomas such as colorectal cancer (CC) and hematologic malignancies such as multiple myeloma (MM). Thus, the Wnt/β-catenin pathway potentially offers an attractive target for cancer therapy. This approach, however, has thus far proved challenging because the pathway plays a number of critical roles in physiological homeostasis, and because drugs that broadly target the pathway have unacceptable side effects. MicroRNAs (miRs) function as regulators of gene expression and have also been implicated in the pathogenesis of MM and other human cancers, offering the promise of novel therapeutic approaches if they can be applied effectively in vivo. Because BCL9 is a critical transcriptional co-activator of β-catenin that is aberrantly expressed in many human cancers but is of low abundance in normal tissues the Wnt/β-catenin/BCL9 complex has emerged as a promising and most likely relatively safe therapeutic target in cancers with dysregulated Wnt/β-catenin activity. This review discusses recent advances in the biology of Wnt inhibitors and the appealing possibility of a functional link between BCL9 and microRNA-30a/b/c/d/e-5p that could be exploited for MM therapy.