Abstract

At present, scientists have performed numerous studies investigating the morbidity of renal cell carcinoma (RCC) in the genetic and microRNA (miRNA) fields, obtaining a substantial amount of knowledge. However, the experimentally validated data of genes, miRNA and transcription factors (TFs) cannot be found in a unified form, which makes it challenging to decipher the regulatory mechanisms. In the present study, the genes, miRNAs and TFs involved in RCC are regarded as elements in the regulatory network, and the present study therefore focuses on the association between each entity. Three regulatory networks were constructed hierarchically to indicate the regulatory association between the genes, miRNAs and TFs clearly, including the differentially expressed, associated and global networks. All the elements were macroscopically investigated in these networks, instead of only investigating one or several of them. The present study not only compared and analyzed the similarities and the differences between the three networks, but also systematically expounded the pathogenesis of RCC and supplied theoretical foundations for future gene therapy investigations. Following the construction of the three networks, certain important pathways were highlighted. The upstream and downstream element table of differentially expressed genes and miRNAs was listed, in which self-adaption associations and circle-regulations were identified. In future studies, the identified genes and miRNAs should be granted more attention.

Highlights

  • Renal cell carcinoma (RCC) is a kidney cancer that derives from the lining of the proximal convoluted tubule and theKey words: transcription factors, microRNA, target genes, host genes, network, renal cell carcinoma small tubes in the kidney that filter the blood to remove waste products

  • There were two transcription factors (TFs), phosphatase and tensin homolog (PTEN) and tumor protein p53 (TP53) in this network, which were regarded as the essential regulatory elements

  • All the currently validated genes and miRNAs associated with RCC were collected in the present study and three regulatory networks were used to analyze the complex regulatory associations of the differentially expressed elements in RCC

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Summary

Introduction

Renal cell carcinoma (RCC) is a kidney cancer that derives from the lining of the proximal convoluted tubule and the. An increasing number of individuals succumb to RCC and studies have begun to focus on the differentially expressed genes and microRNAs (miRNAs) in RCC, the signals and mechanisms that govern miRNA transcriptional regulation remain unclear. The tumor suppressor gene DKK1 induces apoptosis and inhibits proliferation in human RCC cells [3]. The majority of regulatory genes encode transcription factors (TFs), which modulate gene expression by binding the regulatory sequences of their target genes. TFs and miRNAs are prominent regulators of gene expression [4]. TFs are proteins that can activate or repress transcription by binding cis‐regulatory elements, located in the upstream regions of genes and regulate gene expression at the transcriptional level, either individually or joint with other proteins

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