The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

Abstract

Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.

A genome‐wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer

“…Interestingly, these processes are closely related to cancer cells proliferation and invasion. As well as our findings, Sun et al24 reported that DUXAP8 promotes cell proliferation and invasion through repressing EGR1 and RHOB expression in human non small cell lung cancer; Ma et al25 found that DUXAP8 promotes cell proliferation through epigenetically silencing PLEKHO1 expression in gastric cancer. In addition, Kong and colleagues27 revealed that LINC00460 facilitates tumorigenesis by sponging miR‐149‐5p to up‐regulate IL6 in nasopharyngeal carcinoma; Liang et al28 reported that LINC00460 expression is upregulated in ESCC tissues and positively correlated with lymph node metastasis.…”

“…Among these increased lncRNAs, we found that DUXAP8 and LINC00460 are consistently upregulated in TCGA data and three GEO datasets (Figure 4A,B). Interestingly, DUXAP8 has also been reported to be overexpressed in human non small cell lung cancer,24 gastric cancer25 and renal cell carcinoma,26 while LINC00460 expression is upregulated in nasopharyngeal carcinoma27 and promotes carcinogenesis in ESCC 28. Therefore, we chose these two lncRNAs for further analyses and validation.…”

TRIM44 promotes cell proliferation and migration by inhibiting FRK in renal cell carcinoma

“…Of the 12 genes that were downregulated by TRIM44, three genes were found to possess tumor suppressive functions (Figure A; FRK, EGR1 and BCL2L14 ). We then used the Oncomine dataset to analyze the expression level of these three genes in tumors. FRK was the only gene that showed low expression levels in cancer compared with benign tissues (Figures B,C and ).…”

Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis

“…5H and I). The transcriptional factor of EGR1 is expressed in response to various extracellular signals such as growth factors, cytokines, irradiation and various kinds stressors and it has been confirmed that EGR1 plays a significant role as a tumor suppressor in breast, brain, and lung cancer and inhibits growth and transformation when overexpressed [42-44]. SEPW1, a mammalian archetype of the selenoprotein W-like family, is an ubiquitous 9 kDa Sec-containing protein with glutathione-dependent antioxidant activity [45] that promotes tumor growth in breast cancer [26].…”