Retraction Notice to: Upregulation of lncRNA LINC00460 Facilitates GC Progression through Epigenetically Silencing CCNG2 by EZH2/LSD1 and Indicates Poor Outcomes.

[This retracts the article DOI: 10.1016/j.omtn.2019.12.041.].

Upregulation of lncRNA LINC00460 Facilitates GC Progression through Epigenetically Silencing CCNG2 by EZH2/LSD1 and Indicates Poor Outcomes.

Non-protein-coding functional elements in the human genome in the postgenomic biology field have been drawing great attention in recent years. Thousands of long non-coding RNAs (lncRNAs) have been found to be expressed in various tumors. Yet only a small proportion of these lncRNAs have been well characterized. We have demonstrated that LINC00460 could affect cell proliferation through epigenetic regulation of KLF2 and CUL4A in human colorectal cancer. However, the clinical significance and biological role of LINC00460 in gastric cancer (GC) remain largely unknown. In this research, we discovered that LINC00460 is remarkably upregulated in GC tissues compared to the non-tumor tissues. Additionally, LINC00460 served as an independent prognostic marker in GC. Functionally, proliferation of GC cells could be regulated by LINC00460 both in vitro and in vivo. RNA sequencing (RNA-seq) analysis for the whole transcriptome indicated that LINC00460 may serve as a key regulatory factor in the tumorigenesis of GC. What's more, the biological function of LINC00460 was mediated, to certain extent, by the direct interaction with enhancer of zeste homolog 2 (EZH2) and lysine (K)-specific demethylase 1A (LSD1) proteins. Further analyses indicated that LINC00460 promoted GC proliferation at least partly through the downregulation of tumor suppressor-gene Cyclin G2 (CCNG2), which is mediated by EZH2 and LSD1. In conclusion, our results suggested that LINC00460 acted as an oncogene in GC to inhibit the expression of CCNG2 at least partly by binding with EZH2 and LSD1. Our study could provide additional insights into the development of novel target therapeutic methods for GC.

DUXAP8, a pseudogene derived lncRNA, promotes growth of pancreatic carcinoma cells by epigenetically silencing CDKN1A and KLF2.

BACKGROUND: Recent studies highlight pseudogene derived long non-coding RNAs (lncRNAs) as key regulators of cancer biology. However, few of them have been well characterized in pancreatic cancer. Here, we aimed to identify the association between pseudogene derived lncRNA DUXAP8 and growth of pancreatic cancer cells. METHODS: We screened for pseudogene derived lncRNAs associated with human pancreatic cancer by comparative analysis of three independent datasets from GEO. Quantitative real-time reverse transcription polymerase chain reaction was used to assess the relative expression of DUXAP8 in pancreatic cancer tissues and cells. Loss-of-function approaches were used to investigate the potential functional roles of DUXAP8 in pancreatic cancer cell proliferation and apoptosis in vitro and in vivo. RNA immunoprecipitation, chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of DUXAP8 with target proteins and genes in pancreatic cancer cells. RESULTS: Pancreatic cancer tissues had significantly higher DUXAP8 levels than paired adjacent normal tissues. High DUXAP8 expression was associated with a larger tumor size, advanced pathological stage and shorter overall survival of pancreatic cancer patients. Moreover, silencing DUXAP8 expression by siRNA or shRNA inhibited pancreatic cancer cell proliferation and promoted apoptosis in vitro and in vivo. Mechanistic analyses indicated that DUXAP8 regulates PC cell proliferation partly through downregulation of tumor suppressor CDKN1A and KLF2 expression. CONCLUSION: Our results suggest that tumor expression of pseudogene derived lncRNA DUXAP8 plays an important role in pancreatic cancer progression. DUXAP8 may serve as a candidate biomarker and represent a novel therapeutic target of pancreatic cancer.

A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer.

Emerging evidence has proven that long noncoding RNAs (lncRNAs) play important roles in human colorectal cancer (CRC) biology, although few lncRNAs have been characterized in CRC. Therefore, the functional significance of lncRNAs in the malignant progression of CRC still needs to be further explored. In this study, through analyzing TCGA RNA sequencing data and other publicly available microarray data, we found a novel lncRNA, LINC00460, whose expression was significantly upregulated in CRC tissues compared to adjacent normal tissues. Consistently, real-time qPCR results also verified that LINC00460 was overexpressed in CRC tissues and cells. Furthermore, high LINC00460 expression levels in CRC specimens were correlated with larger tumor size, advanced tumor stage, lymph node metastasis and shorter overall survival. In vitro and in vivo assays of LINC00460 alterations revealed a complex integrated phenotype affecting cell growth and apoptosis. Mechanistically, LINC00460 repressed Krüppel-like factor 2 (KLF2) transcription by binding to enhancer of zeste homolog 2 (EZH2). LINC00460 also functioned as a molecular sponge for miR-149-5p, antagonizing its ability to repress cullin 4A (CUL4A) protein translation. Taken together, our findings support a model in which the LINC00460/EZH2/KLF2 and LINC00460/miR-149-5p/CUL4A crosstalk serve as critical effectors in CRC tumorigenesis and progression, suggesting new therapeutic directions in CRC.