E2F1 induces TINCR transcriptional activity and accelerates gastric cancer progression via activation of TINCR/STAU1/CDKN2B signaling axis

Abstract

Recent evidence indicates that E2F1 transcription factor have pivotal roles in the regulation of cellular processes, and is found to be dysregulated in a variety of cancers. Long non-coding RNAs (lncRNAs) are also reported to exert important effect on tumorigenesis. E2F1 is aberrantly expressed in gastric cancer (GC), and biology functions of E2F1 in GC are controversial. The biological characteristics of E2F1 and correlation between E2F1 and lncRNAs in GC remain to be found. In this study, integrated analysis revealed that E2F1 expression was significantly increased in GC cases and its expression was positively correlated with the poor pathologic stage, large tumor size and poor prognosis. Forced E2F1 expression promotes proliferation, whereas loss of E2F1 function decreased cell proliferation by blocking of cell cycle in GC cells. Mechanistic analyses indicated that E2F1 accelerates GC growth partly through induces TINCR transcription. TINCR could bind to STAU1 (staufen1) protein, and influence CDKN2B mRNA stability and expression, thereby affecting the proliferation of GC cells. Together, our findings suggest that E2F1/TINCR/STAU1/CDKN2B signaling axis contributes to the oncogenic potential of GC and may constitute a potential therapeutic target in this disease.

Long Non-Coding RNA Expression Profiles for the Characterization of Different Bladder Cancer Grade

“…More than 80% of the mammalian genome is composed of lncRNAs [8]. Accumulating evidence support that lncRNAs are involved in the malignant process of cancer, such as tumorigenesis and metastasis [9][10][11][12]. During the past years, several dysregulation lncRNAs have been discovered and found to play important roles in bladder cancer.…”

Long non‐coding RNA NNT‐AS1 sponges miR‐424/E2F1 to promote the tumorigenesis and cell cycle progression of gastric cancer

“…Based on the above findings, we conclude that NNT‐AS1 exerts the cycle inhibitive function through targeting miR‐424/E2F1 axis. E2F1 is found to be aberrantly high‐expressed in gastric cancer, and enhanced E2F1 expression promotes proliferation, while E2F1 low expression decreased cell proliferation by blocking cell cycle in GC cells 26. Moreover, R‐424‐5p is found to be up‐regulated in GC tissues and cells, and its high‐expression could promote the proliferation of GC cells 27…”

“…E2F1 is found to be aberrantly high-expressed in gastric cancer, and enhanced E2F1 expression promotes proliferation, while E2F1 low expression decreased cell proliferation by blocking cell cycle in GC cells. 26 Moreover, R-424-5p is found to be up-regulated in GC tissues and cells, and its high-expression could promote the proliferation of GC cells. 27 More than NNT-AS1, other lncRNAs also modulate the cellular process of GC cells.…”

Association between the rs2288947 polymorphism of the lncRNA TINCR gene and the risk of recurrent miscarriage in a Southern Chinese population

“…Multiple studies have revealed that TINCR is involved in tumorigenesis and aberrant expression in multiple human cancers . Moreover, TINCR has been shown to regulate proliferation, migration, and invasion of multiple tumor cells . Recently, studies have found that genetic variation in TINCR was associated with a variety of diseases, such as the SNP rs2288947, which contributed to the susceptibility and progression of colorectal cancer and susceptibility to gastric cancer .…”

“…[12][13][14] Moreover, TINCR has been shown to regulate proliferation, migration, and invasion of multiple tumor cells. [15][16][17][18] Recently, studies have found that genetic variation in TINCR was associated with a variety of diseases, such as the SNP rs2288947, which contributed to the susceptibility and progression of colorectal cancer and susceptibility to gastric cancer. 19,20 Furthermore, studies have found that some genes that regulate cell proliferation, invasion, and migration are associated with susceptibility to miscarriage; for example, H19 and p53 gene polymorphisms.…”