Abstract
BackgroundAccumulated evidences have demonstrated that long non-coding RNAs (lncRNAs) are dysregulated and correlate with the pathophysiological basis of malignant tumors. The objective of this research is to uncover the possible molecular mechanism of MACC1-AS1 regarding the regulation of pancreatic carcinoma (PC) metastasis.MethodslncRNA microarray and qRT-PCR were applied to identify differentially expressed lncRNA profile in PC. The function and role of MACC1-AS1 in PC were assessed via in vitro as well as in vivo assays. Luciferase analyses, RNA immunoprecipitation, and RNA pull-down were performed to determined the underlying MACC1-AS1 mechanisms.ResultsNumbers of differentially expressed lncRNAs in PC were identified via lncRNA microarrays, among which MACC1-AS1 was revealed as the most abundant lncRNA. The upregulation of MACC1-AS1 in PC was further confirmed in two expanded PC cohorts, which showed that MACC1-AS1 expression was upregulated in those PC patients with poor survival. Functionally, knockdown of MACC1-AS1 inhibited the proliferation as well as metastasis of PC cells. Meanwhile, MACC1-AS1 upregulated the expression of PAX8 protein, which promoted aerobic glycolysis and activated NOTCH1 signaling. Additionally, PAX8 was upregulated in PC tissues, which was correlated with the expression of MACC1-AS1 and the overall survival of PC patients.ConclusionsTogether, our findings indicate a critical role of MACC1-AS1/PAX8/NOTCH1 signaling, which may be an alternative treatment target in PC therapy.
Highlights
Accumulated evidences have demonstrated that long non-coding RNAs are dysregulated and correlate with the pathophysiological basis of malignant tumors
This study revealed that MACC1-AS1 played a regulatory role in NOTCH1 signaling and glycolysis via PAX8 in pancreatic carcinoma (PC), suggesting that MACC1-AS1 might serve as an novel treatment target for PC
MACC1-AS1 expression was increased in PC tissues and indicates bad prognosis LncRNA expression levels in five paired PCs and noncancerous tissues (NCTs) were detected to identify differentially expressed long non-coding RNAs (lncRNAs) in PC
Summary
Accumulated evidences have demonstrated that long non-coding RNAs (lncRNAs) are dysregulated and correlate with the pathophysiological basis of malignant tumors. The objective of this research is to uncover the possible molecular mechanism of MACC1-AS1 regarding the regulation of pancreatic carcinoma (PC) metastasis. Pancreatic carcinoma (PC) is the fourth leading cause of cancer-related death, which is one of the most aggressive tumors [1, 2]. The tumor would remain concealed in the early stages, whereas it could progress fast; the disease of most patients is found during the advanced stage [4]. Recent findings have uncovered that approximately 98% of human genome transcripts are ncRNAs, which have little or even no protein-coding capability [5]. LncRNAs, Some lncRNAs, including NORAD, PVT1, and CASC2, are reported with aberrant expressions in PC, which can regulate tumorigenesis and progression of PC [8,9,10]. The mechanisms and functions of them in PC are poorly known
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