Prediction of regulatory modules comprising microRNAs and target genes
BIOINFORMATICS
Authors: Yoon, SR; De Micheli, G
Abstract
Motivation: MicroRNAs (miRNAs) are small endogenous RNAs that can play important regulatory roles via the RNA-interference pathway by targeting mRNAs for cleavage or translational repression. We propose a computational method to predict miRNA regulatory modules (MRMs) or groups of miRNAs and target genes that are believed to participate cooperatively in post-transcriptional gene regulation. Results: We tested our method with the human genes and miRNAs, predicting 431 MRMs. We analyze a module with genes: BTG2, WT1, PPM1D, PAK7 and RAB9B, and miRNAs: miR-15a and miR-16. Review of the literature and annotation with Gene Ontology terms reveal that the roles of these genes can indeed be closely related in specific biological processes, such as gene regulation involved in breast, renal and prostate cancers. Furthermore, it has been reported that miR-15a and miR-16 are deleted together in certain types of cancer, suggesting a possible connection between these miRNAs and cancers. Given that most known functionalities of miRNAs are related to negative gene regulation, extending our approach and exploiting the insight thus obtained may provide clues to achieving practical accuracy in the reverse-engineering of gene regulatory networks. Availability: A list of predicted modules is available from the authors upon request.
Over expression of p21-activated kinase 7 associates with lymph node metastasis in esophageal squamous cell cancers
CANCER BIOMARKERS
Authors: He, Shun; Liu, Mei; Zhang, Weina; Xu, Ningzhi; Zhu, Hongxia
Abstract
BACKGROUND: p21-activated kinase 7 is a member of the group II p21-activated kinase (PAK) family which is known to play important role in tumorigenesis and metastasis. However, the expression of p21-activated kinase 7 in esophageal squamous cell cancers and the correlation with clinical parameters has never been investigated. OBJECTIVE: To explore the role of p21-activated kinase 7 in esophageal squamous cell cancers. METHODS: Esophageal squamous cell carcinoma samples were collected and the expression of p21-activated kinase 7 was detected by immunohistochemistry. In vitro cell invasion assay was employed in EC9706 cells and EC9706PAK7 cells. Metastasis related genes were evaluated by Real-time PCR and Western Blot. RESULTS: In 85 samples, 44 (51.8%) samples showed strong expression and expression of PAK7 was significantly correlated with lymph node stage (p = 0.013) and TNM stage (p = 0.041). In vitro invasion assay showed that the invasion ability of EC9706 PAK7 cells increased 2.5 folds compared with EC9706 cells. PAK7 could enhance the protein levels of Vimentin and MMP10, but reduce E-cadherin, TIMP1 and TIMP2. CONCLUSION: PAK7 is overexpressed in human esophageal squamous cell cancer samples and correlated with lymph node metastasis.