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A transcribed pseudogene of MYLK promotes cell proliferation.

ABSTRACT: 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 (? 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.

SUBMITTER: Han YJ

PROVIDER: S-EPMC6137860 | biostudies-other | 2011 Jul

REPOSITORIES: biostudies-other

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A transcribed pseudogene of MYLK promotes cell proliferation.

Han Yoo Jeong YJ Ma Shwu Fan SF Yourek Gregory G Park Yoon-Dong YD Garcia Joe G N JG

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20110325 7

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 regu ...[more]

PMID: 21441351

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Project description:ObjectivesPreeclampsia (PE), a pregnancy-specific disorder characterized by hypertension and a variety of organ failures, currently lacks effective treatments. Urate (hydroxyiso-) hydrolase, pseudogene (URAHP), which is also a long noncoding RNA (lncRNA), has higher expression in PE placentae than in normal controls and therefore acquires an investigation for the specific mechanism of regulation.MethodsPlacentae were divided into two groups: those from patients with normal pregnancy (NP) (n = 3) and those from patients with PE (n = 3). Total RNA was extracted from the placentae and differentially expressed lncRNAs and mRNAs in PE and NP were identified by Arraystar Human LncRNA Expression Microarray V4.0 analysis. The microarray data were validated by profiling the noncoding RNA expression of URAHP in NP and PE placental tissues through quantitative real-time PCR (qRT-PCR). Then, we uncover the effect of URAHP on cell proliferation by CCK-8 assay and by 3D colony forming assay. Gene coexpression analysis was conducted to identify mRNAs coexpressed with URAHP. qRT-PCR and western blotting assays were used to measure the expression levels of URAHP and KISS1R in JAR and JET-3 cell lines.ResultsA total of 675 differentially expressed lncRNAs (DELRs) [184 upregulated DELRs and 491 downregulated DELRs] and a total of 205 differently expressed genes (DEGs) [56 upregulated mRNAs and 149 downregulated mRNAs] were finally identified between PE and NP samples through high-throughput sequencing analysis. The expression of lncRNA URAHP was increased significantly in the placentae of women with preeclampsia when compared to those with normal pregnancies. The functional assay suggested that the downregulation of URAHP alters the proliferative capacity of JAR/JET-3 cells and that the overexpression of URAHP promotes the proliferation of HTR-8/SVneo cells. We also determined that URAHP and KISS1R are coexpressed.ConclusionWe demonstrated for the first time that the pseudogene URAHP may be associated with PE. The results of this study provide a new target for the comprehensive treatment of preeclampsia.

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A transcribed pseudogene of MYLK promotes cell proliferation.

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A transcribed pseudogene of MYLK promotes cell proliferation.

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