Long non-coding RNA MACC1-AS1 promoted pancreatic carcinoma progression through activation of PAX8/NOTCH1 signaling pathway

• Published in: Journal of experimental & clinical cancer research 2019-08, Vol.38 (1), p.344-344
• Main Authors: Qi, Chen, Xiaofeng, Chen, Dongen, Li, Liang, Yang, Liping, Xu, Yue, Hu, Jianshuai, Jiang
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Apoptosis - genetics; Biomarkers, Tumor; Cancer metastasis; Carcinoma; Care and treatment; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cellular signal transduction; Development and progression; Disease Models, Animal; Disease Progression; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic aspects; Glucose metabolism; Humans; Immunohistochemistry; Long ncRNAs (lncRNAs); Luciferase; Male; Metastasis; Mice; Middle Aged; Models, Biological; Pancreatic cancer; Pancreatic carcinoma (PC); Pancreatic Neoplasms; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; PAX8 Transcription Factor - metabolism; Prognosis; Proliferation; Pyruvate kinase M2 (PAX8); Receptor, Notch1 - metabolism; RNA; RNA, Long Noncoding - genetics; Signal Transduction; Trans-Activators - genetics; Tumors; Xenograft Model Antitumor Assays
• ISSN: 0392-9078; 1756-9966
• DOI: 10.1186/s13046-019-1332-7

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. lncRNA 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. Numbers 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. Together, our findings indicate a critical role of MACC1-AS1/PAX8/NOTCH1 signaling, which may be an alternative treatment target in PC therapy.