Long noncoding RNA DINO (damage induced noncoding) represses the development of gastric cancer by modulating p21 and Bcl‐2 Associated X Protein (Bax) expression

Abstract

lncRNAs are responsible for a variety of diseases, including gastric cancer (GC). Many recent studies have reported that lncRNAs can serve as crucial regulators of various genes. Nevertheless, the biological function of lncRNA damage induced noncoding (DINO) remained poorly investigated in GC. Therefore, in our present study, the detailed role of DINO was investigated. It was manifested that DINO was significantly downregulated in GC tissues. Then, DINO was modulated by infecting LV-DINO or by LV-shRNA in BGC-823 and MGC-803 cells. Moreover, it was displayed that GC cell proliferation was suppressed by DINO overexpression, whereas silencing DINO increased cell proliferation significantly. For another, it was indicated that DINO dramatically induced apoptotic ratios of BGC-823 and MGC-803 cells, whereas the decrease of DINO depressed GC cell apoptosis. Apart from these, GC cell cycle progression was greatly blocked by LV-DINO. Furthermore, Western blot results displayed that upregulation of DINO elevated p21 expression and Bax expression. Oppositely, inhibition of DINO greatly suppressed p21 and Bax protein expression level. Taken these, DINO might exert a tumor inhibitory role in the progression of GC through modulating p21 and Bax. K E Y W O R D SBax, damage induced noncoding (DINO), gastric cancer (GC), p21 Recently, the roles of lncRNAs in GC process have been elucidated in details. For example, MDC1-AS can inhibit GC cell proliferation and metastasis through regulating MDC1. 9 MACC1-AS1 promotes GC cell metabolic plasticity through modulating AMPK, Lin28, and MACC1. 10 Besides, CASC15 can regulate GC cell proliferation, migration, and J Cell Biochem. 2019;120:11190-11195. wileyonlinelibrary.com/journal/jcb 11190 |

A Unique Spectrum of Spontaneous Tumors in Dino Knockout Mice Identifies Tissue-Specific Requirements for Tumor Suppression

“…While p53 -null mice predominantly develop spontaneous T lymphomas of thymic origin, we were surprised to observe no incidence of T cell lymphoma in Dino −/− mice ( Table 1 ) [ 18 , 26 ]. Given the well-established role of Dino in p53 pathway regulation in multiple cell types, including T cells [ 16 , 17 , 27 ], the absence of spontaneous T cell lymphoma in Dino -null mice is particularly striking. p53 is critical for the protection of cells against radiation-induced carcinogenesis [ 28 ], particularly in the thymus, which undergoes extensive p53-dependent apoptosis after radiation [ 29 , 30 ].…”

Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications

“…In addition, in cervical cancer cells, it has been shown that DINO activation occurs through a pathway that is independent of ATM/CHK2 ( Sharma and Munger 2020a ). Recent studies show that DINO is silenced in human cancers ( Liu et al, 2019 ; Marney et al, 2021 ), and some evidence shows that a region of the DINO/CDKN1A locus is hypermethylated, leading to the silencing of DINO but not CDKN1A ( Marney et al, 2021 ). Furthermore, silencing DINO in a model of primary HFKs E7+ HPV16+ using shRNAs decreases sensitivity to doxorubicin ( Sharma and Munger 2020b ).…”

LncRNAs-associated to genomic instability: A barrier to cancer therapy effectiveness

“…Using the TCGA Pan-Cancer database, it was found that many tumors have methylation in the CpG shore downstream of the DINO TSS associated with lower expression, which would explain the low mutation rate in this gene ( Marney et al, 2021 ). In tumors of patients with gastric cancer, DINO is downregulated compared to adjacent tissue ( Liu et al, 2019 ).…”