Abstract
Emerging evidence has demonstrated that circular RNAs (circRNAs) take part in the initiation and development of pancreatic ductal adenocarcinoma (PDA), a deadly neoplasm with an extremely low 5-year survival rate. Reprogrammed glucose metabolism is a key feature of tumour development, including PDA. In this research, we evaluated the role of circRNAs in reprogrammed glucose metabolism in PDA. RNA sequencing under various glucose incubation circumstances was performed. A new circMYOF was identified. Sanger sequencing and RNase R treatment confirmed its circular RNA characteristics. Real-time PCR indicated that it was highly expressed in PDA clinical specimens and cell lines. Gain-of- and loss-of-function assays showed that circMYOF induced progression in PDA. Mechanistically, RNA pull-down and luciferase reporter experiments elucidated that circMYOF, as a competing endogenous RNA for miR-4739, facilitated glycolysis via the VEGFA/PI3K/AKT pathway. Taken together, our findings indicate that circMYOF may work as a desirable biomarker and therapeutic target for PDA patients.
Highlights
Pancreatic ductal adenocarcinoma (PDA) is a fatal malignancy with extremely high morbidity and mortality
The results showed that circMYOF was primarily cell lines, and constructed a circRNA profiling localized in the cytoplasm (Fig. 1G), which revealed that circMYOF
Volcano plot analysis revealed that circMYOF was one of the most CircMYOF plays an oncogenic role in PDA in vitro and in vivo overexpressed circRNAs under abnormal glucose conditions To assess the biological role of circMYOF, gain-of- and loss-of
Summary
Pancreatic ductal adenocarcinoma (PDA) is a fatal malignancy with extremely high morbidity and mortality. Reprogrammed glucose metabolism, known as the Warburg effect, is a hallmark of malignancy [4, 5] It exhibits increased aerobic glycolysis, glucose uptake and lactate production. Different from linear RNAs ending with 5’ caps and 3’ tails, circRNAs are characterized by the structures of covalently closed loops Due to their conservation, tissue abundance and specificity, circRNAs may function importantly in tumour development, including PDA [27,28,29]. RNA (ceRNA) for miR-4739, facilitated glycolysis via the VEGFA/ was conducted to illustrate the stability of circMYOF.
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