Regulatory network analysis of LINC00472, a long noncoding RNA downregulated by DNA hypermethylation in colorectal cancer

Abstract

Colorectal cancer (CRC), one of the common malignant cancers in the world, is caused by accumulated alterations of genetic and epigenetic factors over a long period of time. Along with that protein-coding genes being identified as oncogenes or tumor suppressors in CRC, a number of lncRNAs have also been found to be associated with CRC. Considering the important regulatory role of lncRNAs, the first goal of this study was to identify CRC-associated lncRNAs from a public database. One such lncRNA, LINC00472, was verified to be downregulated in CRC cell lines and cancer tissues compared with adjacent tissues. In addition, the down-regulation of LINC00472 seemed to be caused by DNA hypermethylation at its promoter region. Furthermore, the expression of LINC00472 and DNA methylation of promoter were significantly correlated with clinicopathological features. And DNA hypermethylation of LINC00472 may serve as a better diagnostic biomarker than its expression for CRC. Finally, we predicted the functions of LINC00472 and constructed a regulatory network and found LINC00472 may be involved in cell cycle and cell proliferation processes. Our results may provide a clue to further research into the function and regulatory mechanism of LINC00472 in CRC.

Linc00472 suppresses proliferation and promotes apoptosis through elevating PDCD4 expression by sponging miR-196a in colorectal cancer

“…In the present study, we found that Linc00472 expression was decreased in CRC tissues, further verified by TCGA cohort. In parallel with our study, two latest publications also revealed low Linc00472 expression presented in CRC [ 15 , 24 ]. Our study further demonstrated that Linc00472 suppressed proliferation and induced apoptosis in CRC cells.…”

Up-regulated Linc00472 suppresses development of lung cancer cell via inhibition of MiR-196b-5p

“…Increasingly research indicated the effect of lncRNAs on various diseases, including lung cancers [8]. linc00472 expression was associated with less aggressive cancer and more favorable disease outcomes of breast cancer [9] and colorectal cancer [10]. However, until now, the role and molecular mechanism of linc00472 in the LC development are still not clarified yet.…”

Prediction of Specific Subtypes and Common Markers of Non-Small Cell Lung Cancer Based on Competing Endogenous RNA Network

“…Therefore, we extracted 1 step of neighbor nodes of 2 networks with degree of nodes greater than 20 and maintained the original connection. These nodes that participate in multiple connections in the network are defined as markers such as oncogene PVT1 [ 20 , 21 ], LINC00472 [ 22 ], multiple tumor suppressor CDKN2A [ 23 ], prognostic Biomarkers in NSCLC FAM83B [ 24 ], cancer susceptibility gene BRCA2 in LUSC and HOXA11-AS [ 25 ], HNF1A-AS1 [ 26 ], LINC00511 [ 27 , 28 ], and HOTAIR [ 29 – 32 ] in LUAD ( Figure 4A, 4B ). There are many genes in this network that are significantly associated with survival of patients with 2 types of cancer ( Figure 5 ).…”