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

Abstract

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.

LINC00460/DHX9/IGF2BP2 complex promotes colorectal cancer proliferation and metastasis by mediating HMGA1 mRNA stability depending on m6A modification

“…LINC00460 is located on chromosome 13q33.2 and is transcribed into a 935 bp transcript; this lncRNA has recently been reported in several cancers. Most recently, several studies have shown LINC00460 was overexpressed in multiple cancers, such as gastric cancer [ 15 ], lung cancer [ 16 ], head and neck squamous cell carcinoma (HNSCC) [ 17 ], hepatocellular carcinoma [ 18 ] and colon cancer [ 19 , 20 ]. Studies showed that LINC00460 mainly located in cytoplasm and could bind to miRNAs to affect CRC progression [ 19 , 20 ].…”

Integrated Analysis of lncRNA–Mediated ceRNA Network in Lung Adenocarcinoma

“…H19 has also been shown to be a prognostic biomarker in bladder cancer (25). LINC00518 and LINC00460 act as oncogenes to facilitate tumor progression, including prostate cancer (44), gastric cancer (45), colon cancer (46), and lung cancer (47). Relevant studies on the function of DISC1-IT1, SYNPR-AS1 DSCR10, STEAP2-AS1, and hsa-mir-31 in cancer do not exist in the literature.…”

<p>LncRNA CTBP1-AS2 Facilitates Gastric Cancer Progression via Regulating the miR-139-3p/MMP11 Axis</p>

“… 19 For example, lncRNA DRAIC is down-regulated in GC, and it can interact with UCHL5 to mediate NFRKB ubiquitination, in turn suppress the tumorigenesis of GC; 20 LINC00460 is overexpressed in GC tissues, and it facilitate the proliferation, migration and invasion of GC cells by epigenetically silencing tumor suppressor CCNG2. 9 LncRNA CTPB1-AS2 is a newly discovered lncRNA, and its function and mechanism in cancer biology is rarely investigated. A recent study reports that CTBP1-AS2 expression is significantly related to recurrence-free survival time of patients with papillary thyroid cancer, showing its potential to be used as a cancer-related biomarker.…”

“…[5][6][7] For instance, as an oncogenic lncRNA, lncRNA AFDN-DT can inhibit GC cell growth through transcriptional regulation; 8 as a tumorsuppressive factor, LINC00460 is significantly upregulated in GC tissues, and promotes the malignant biological behaviors of cancer cells via epigenetically silencing CCNG2. 9 LncRNA C-terminal binding protein 1 antisense RNA 2 (CTBP1-AS2) is not only related to the susceptibility to type 2 diabetes 10 but also closely connected with the recurrence of papillary thyroid cancer. 11 Nevertheless, the role of CTBP1-AS2 in cancer biology, especially in GC, is still unclear.…”