Abstract
LncRNAs play essential regulatory roles in pancreatic cancer (PC) tumorigenesis and progression. We aimed to investigate the role of lncRNA CERS6-AS1 in PC. CERS6-AS1 expression was determined in PC tissues and cell lines by PCR analysis. The roles of CERS6-AS1 on proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) were confirmed via CCK-8 assay, EDU assay, transwell assay, wound healing assay, and western blot assay. Besides, the interaction between CERS6-AS1 and their target genes was verified by luciferase report assays and RIP assays. Animal assays and clinical data analysis were performed to validate the functions in vivo. We found that lncRNA CERS6-AS1 was highly expressed in PC tissues and cells. Additionally, high expression of CERS6-AS1 was obviously associated with poor prognosis. Functional assays demonstrated that CERS6-AS1 downregulation significantly inhibited PC cell growth and migration. Moreover, CERS6-AS1 exerted as a molecular sponge for miR-217-5p (miR-217), and miR-217 was confirmed as a potential target of CERS6-AS1. Subsequently, miR-217 suppressed PC cell proliferation and metastasis by directly targeting YWHAG, which interacted with RAF1 and promoted its phosphorylation, leading to RAF1-mediated ERK signaling activation and translocation of phosphorylated ERK from the cytoplasm to the nucleus. Mechanically, CERS6-AS1 silencing significantly inhibited PC cell proliferation and metastasis via a miR-217/YWHAG/RAF1 signaling axis. CERS6-AS1 exerts as a carcinogen in PC to promote malignant features and behaves as a competitive endogenous RNA for miR-217. We identified CERS6-AS1 as a potential biomarker or therapeutic target to improve PC diagnosis and treatment outcomes.
Highlights
Pancreatic cancer (PC) is a highly malignant digestive cancer with a high mortality rate and a 5-year survival rate of less than 10% [1]
CERS6-AS1 expression is upregulated in PC and associated with a poor prognosis To analyze the involvement of differentially expressed Long non-coding RNAs (lncRNAs) in PC, we investigated the lncRNAs with markedly different expression via the gene expression profiling interactive analysis (GEPIA) network database, which is based on TCGA datasets
To further confirm the expression of CERS6-AS1 in PC tissues, we measured the mRNA level of CERS6-AS1 in PC tissues and their paired adjacent non-tumor tissues by qRT-PCR, and the results suggested that CERS6-AS1 expression was significantly elevated in PC tissues (Fig. 1B)
Summary
Pancreatic cancer (PC) is a highly malignant digestive cancer with a high mortality rate and a 5-year survival rate of less than 10% [1]. There is an urgent need to elucidate the underlying molecular mechanism of PC and explore effective biomarkers and novel therapeutic targets to achieve better-individualized treatment and improve the prognosis of PC patients. LncRNA FLVCR1AS1 functioned as an oncogene to promote ovarian cancer cell progression, metastasis, and epithelial to mesenchymal transition (EMT) by competitively binding to miR-513 to activate YAP1 signaling [6]. Qin et al suggested that lncRNA LINC00657 inhibited cervical cancer progression by functioning as a competitive endogenous RNA (ceRNA) and sponging miR20a-5p [7]. This prevented miR-20a-5p from binding and suppressing RUNX3 mRNA, thereby enhancing RUNX3/DR5mediated NK cell susceptibility [7]. The function and underlying molecular mechanism of CERS6-AS1 in PC remain poorly understood
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