A transcribed pseudogene of MYLK promotes cell proliferation
A transcribed pseudogene of MYLK promotes cell proliferation
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DOI：
10.1096/fj.10-177808
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发表时间：
2011-07-01
期刊：
影响因子：
4.8
通讯作者：
Garcia, Joe G. N.
中科院分区：
文献类型：
--
作者：
Han, Yoo Jeong;Ma, Shwu Fan;Garcia, Joe G. N.
假基因被认为是灾难性途径的无功能基因组产物。然而，近期的证据表明假基因作为基因表达的调节因子具有新的作用。我们通过逆转录聚合酶链反应（RT - PCR）、启动子活性以及细胞增殖实验检测了肌球蛋白轻链激酶假基因（MYLKP1）在人类细胞和组织中的功能。MYLKP1部分复制自编码非肌肉和平滑肌肌球蛋白轻链激酶（smMLCK）异构体并调节细胞收缩性和胞质分裂的原始MYLK基因。尽管与smMLCK启动子有高度同源性（约89.9%），但MYLKP1启动子在正常支气管上皮细胞中活性极低，而在肺腺癌细胞中活性很高。此外，在正常细胞和癌细胞中，MYLKP1和smMLCK呈现负相关的转录模式，MYLKP1在癌细胞中强烈表达，而smMLCK在非肿瘤细胞中高度表达。例如，与正常结肠组织相比，结肠癌组织中smMLCK的表达降低了（19.5 ± 4.7倍）。从机制上讲，MYLKP1的过表达通过降低RNA稳定性抑制癌细胞中smMLCK的表达，从而导致细胞增殖增加。这些研究为假基因在癌症发生中的功能参与提供了有力证据，并表明MYLKP1是人类癌症中一个潜在的新型诊断或治疗靶点。——韩（Han），Y. J.；马（Ma），S. F.；尤雷克（Yourek），G.；朴（Park），Y. - D.；加西亚（Garcia），J. G. N.《MYLK的一个转录假基因促进细胞增殖》，《美国实验生物学会联合会杂志》25卷，2305 - 2312页（2011年），网址：www.fasebj.org
Pseudogenes are considered nonfunctional genomic artifacts of catastrophic pathways. Recent evidence, however, indicates novel roles for pseudogenes as regulators of gene expression. We tested the functionality of myosin light chain kinase pseudogene (MYLKP1) in human cells and tissues by RT-PCR, promoter activity, and cell proliferation assays. MYLKP1 is partially duplicated from the original MYLK gene that encodes nonmuscle and smooth muscle myosin light chain kinase (smMLCK) isoforms and regulates cell contractility and cytokinesis. Despite strong homology with the smMLCK promoter (similar to 89.9%), the MYLKP1 promoter is minimally active in normal bronchial epithelial cells but highly active in lung adenocarcinoma cells. Moreover, MYLKP1 and smMLCK exhibit negatively correlated transcriptional patterns in normal and cancer cells with MYLKP1 strongly expressed in cancer cells and smMLCK highly expressed in non-neoplastic cells. For instance, expression of smMLCK decreased (19.5 +/- 4.7 fold) in colon carcinoma tissues compared to normal colon tissues. Mechanistically, MYLKP1 overexpression inhibits smMLCK expression in cancer cells by decreasing RNA stability, leading to increased cell proliferation. These studies provide strong evidence for the functional involvement of pseudogenes in carcinogenesis and suggest MYLKP1 as a potential novel diagnostic or therapeutic target in human cancers.-Han, Y. J., Ma, S. F., Yourek, G., Park, Y.-D., Garcia, J. G. N. A transcribed pseudogene of MYLK promotes cell proliferation. FASEB J. 25, 2305-2312 (2011). www.fasebj.org