Abstract
BackgroundPancreatic cancer (PC) is one of the most aggressive cancers and has an extremely poor prognosis worldwide. Long noncoding RNA (lncRNA) has been reported to be a potential prognostic biomarker in the initiation and prognosis of PC. Nevertheless, the biological functions and the detailed molecular mechanism of LINC00514 in PC remain unclear.MethodsWe measured the expression level of LINC00514 in PC tissues and cell lines by quantitative real-time PCR. Gain- and loss-of-function experiments were performed to explore the bioeffects of LINC00514 on PC development both in vitro and in vivo. Subcellular fractionation, luciferase reporter assay, RNA immunoprecipitation assay, pull-down assay and western blotting were performed to investigate the oncogenic molecular mechanisms of LINC00514.ResultsIn this study, LINC00514 was shown to be upregulated in PC tissues and cell lines. Increased LINC00514 expression was significantly associated with the clinical progression and prognosis of PC patients. In addition, silencing LINC00514 inhibited PC cell proliferation, migration and invasion, while LINC00514 overexpression promoted these processes. Moreover, LINC00514 knockdown remarkably inhibited PC development and metastasis in vivo. Deeper investigations indicated that LINC00514 acted as a sponge for microRNA-28-5p (miR-28-5p) in PC and that Rap1b was a downstream target of miR-28-5p. Furthermore, the positive correlation of LINC00514 and Rap1b and the negative correlation between miR-28-5p and LINC00514 (or Rap1b) were revealed. Based on the rescue assays, Rap1b inhibition partially suppressed the oncogenic effect of LINC00514 overexpression on PC cell proliferation, migration and invasion.ConclusionsThis study is the first to characterize the oncogenic function of the long noncoding RNA LINC00514 in pancreatic cancer progression by acting as a competing endogenous RNA (ceRNA) of miR-28-5p to upregulate Rap1b expression. Understanding this molecular mechanism might contribute to further discoveries of better diagnostic and therapeutic options for pancreatic cancer.
Highlights
Pancreatic cancer (PC) is one of the most aggressive cancers and has an extremely poor prognosis worldwide
We discovered that LINC00514 expression was increased in PC tissue and PC cell lines and that the upregulated expression of LINC00514 was associated with PC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo
LINC00514 was upregulated in PC and predicted a poor prognosis First, we analyzed the LINC00514 profile in PC
Summary
Pancreatic cancer (PC) is one of the most aggressive cancers and has an extremely poor prognosis worldwide. Long noncoding RNA (lncRNA) has been reported to be a potential prognostic biomarker in the initiation and prognosis of PC. The biological functions and the detailed molecular mechanism of LINC00514 in PC remain unclear. As an extremely aggressive cancer worldwide, pancreatic cancer (PC) has shown an increasing incidence rate in recent years [1]. Due to its high level of malignancy, PC has become the fourth leading cause of death from malignant tumors with poor prognosis, and the 5-year survival rate is less than 5% [2, 3]. In recent years, scientists have found that lncRNAs execute their biological effects in epigenetics [6] at the histone modification [7], transcriptional and posttranscriptional levels [8]. LncRNA SNHG1, which can be positively regulated by miR-21, activates the AKT pathway to promote sorafenib resistance in hepatocellular carcinoma cells [12]; lncRNA EPB41L4AAS1 suppresses the Warburg effect and plays a significant role in metabolic reprogramming of cancer [13]; lncGata could maintain stemness of intestinal stem cells and promote tumorigenesis of colorectal cancer [14]
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