Comprehensive Genomic Characterization Analysis Identifies an Oncogenic Pseudogene RP11-3543B.1 in Human Gastric Cancer

Abstract

Background: Gastrointestinal Cancer (GICs) is the most common group of malignancies, and many of its types are the leading causes of cancer related death worldwide. Pseudogenes have been revealed to have critical regulatory roles in human cancers. The objective of this study is to comprehensive characterize the pseudogenes expression profiling and identify key pseudogenes in the development of gastric cancer (GC).Methods: The pseudogenes expression profiling was analyzed in six types of GICs cancer from The Cancer Genome Atlas RNA-seq data to identify GICs cancer related pseudogenes. Meanwhile, the genomic characterization including somatic alterations of pseudogenes was analyzed. Then, CCK8 and colony formation assays were performed to evaluate the biological function of RP11-3543B.1 and miR-145 in gastric cancer cells. The mechanisms of pseudogene RP11-3543B.1 in GC cells were explored via using bioinformatics analysis, next generation sequencing and lucifarese reporter assay.Results: We identified a great number of pseudogenes with significantly altered expression in GICs, and some of these pseudogenes expressed differently among the six cancer types. The amplification or deletion in the pseudogenes-containing loci involved in the alterations of pseudogenes expression in GICs. Among these altered pseudogenes, RP11-3543B.1 is significantly upregulated in gastric cancer. Down-regulation of RP11-3543B.1 expression impaired GC cells proliferation both in vitro and in vivo. RP11-3543B.1 exerts oncogene function via targeting miR-145-5p to regulate MAPK4 expression in gastric cancer cells.Conclusion: Our study reveals the potential of pseudogenes expression as a new paradigm for investigating GI cancer tumorigenesis and discovering prognostic biomarkers for patients.

Prognostic Roles of ceRNA Network-Based Signatures in Gastrointestinal Cancers

“…Besides, many pseudogenes can also crosstalk with protein-coding genes by acting as ceRNAs to sequester shared miRNAs. For example, RP11-3543B.1 has been identified as an oncogenic pseudogene that implicated in GC pathogenesis by regulating MAPK4 expression via a ceRNA mechanism ( 14 ). However, there is little evidence for pseudogene-related prognostic signatures in GICs.…”

Pseudogene MSTO2P Interacts with miR-128-3p to Regulate Coptisine Sensitivity of Non-Small-Cell Lung Cancer (NSCLC) through TGF-β Signaling and VEGFC

“…Hence, pseudogenes were initially believed to be nonfunctional RNAs [9]. Recently, increasing evidence has shown that pseudogenes could regulate the progression of various tumors [10][11][12]. e Misato family member 2 (MSTO2P) pseudogene was found to be implicated in gastric cancer [13], lung cancer [14] and HCC [15].…”