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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | Research

FUS-induced circRHOBTB3 facilitates cell proliferation via miR-600/NACC1 mediated autophagy response in pancreatic ductal adenocarcinoma

Authors: Taoyue Yang, Peng Shen, Qun Chen, Pengfei Wu, Hao Yuan, Wanli Ge, Lingdong Meng, Xumin Huang, Yuzhe Fu, Yihan Zhang, Weikang Hu, Yi Miao, Zipeng Lu, Kuirong Jiang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Circular RNAs (circRNAs) are becoming a unique member of non-coding RNAs (ncRNAs) with emerging evidence of their regulatory roles in various cancers. However, with regards to pancreatic ductal adenocarcinoma (PDAC), circRNAs biological functions remain largely unknown and worth investigation for potential therapeutic innovation.

Methods

In our previous study, next-generation sequencing was used to identify differentially expressed circRNAs in 3 pairs of PDAC and adjacent normal tissues. Further validation of circRHOBTB3 expression in PDAC tissues and cell lines and gain-and-loss function experiments verified the oncogenic role of circRHOBTB3. The mechanism of circRHOBTB3 regulatory role was validated by pull-down assays, RIP, luciferase reporter assays. The autophagy response of PANC-1 and MiaPaca-2 cells were detected by mCherry-GFP-LC3B labeling and confocal microscopy, transmission electron microscopy and protein levels of LC3B or p62 via Western blot.

Results

circRHOBTB3 is highly expressed in PDAC cell lines and tissues, which also promotes PDAC autophagy and then progression in vitro and in vivo. Mechanistically, circRHOBTB3 directly binds to miR-600 and subsequently acts as a miRNA-sponge to maintain the expression level of miR-600-targeted gene NACC1, which facilitates the autophagy response of PDAC cells for adaptation of proliferation via Akt/mTOR pathway. Moreover, the RNA-binding protein FUS (FUS) directly binds to pre-RHOBTB3 mRNA to mediate the biogenesis of circRHOBTB3. Clinically, circRHOBTB3, miR-600 and NACC1 expression levels are correlated with the prognosis of PDAC patients and serve as independent risk factors for PDAC patients.

Conclusions

FUS-mediated circRHOBTB3 functions as a tumor activator to promote PDAC cell proliferation by modulating miR-600/NACC1/Akt/mTOR axis regulated autophagy.

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Title: FUS-induced circRHOBTB3 facilitates cell proliferation via miR-600/NACC1 mediated autophagy response in pancreatic ductal adenocarcinoma
Authors: Taoyue Yang
Peng Shen
Qun Chen
Pengfei Wu
Hao Yuan
Wanli Ge
Lingdong Meng
Xumin Huang
Yuzhe Fu
Yihan Zhang
Weikang Hu
Yi Miao
Zipeng Lu
Kuirong Jiang
Publication date: 01-12-2021
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-02063-w

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Abstract

Background

Methods

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Conclusions

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