circCUL2 regulates gastric cancer malignant transformation and cisplatin resistance by modulating autophagy activation v
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RESEARCH
Open Access
circCUL2 regulates gastric cancer malignant transformation and cisplatin resistance by modulating autophagy activation via miR142-3p/ROCK2 Lei Peng1†, Huaiming Sang1†, Shuchun Wei1,2†, Yuanyuan Li3†, Duochen Jin1, Xudong Zhu1, Xuan Li1, Yini Dang1 and Guoxin Zhang1*
Abstract Background: Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) and can modulate gene expression by binding to miRNAs; further, circRNAs have been shown to participate in several pathological processes. However, the expression and biological function of circCUL2 in gastric cancer (GC) remains largely unknown. Methods: circRNA microarrays and quantitative real-time PCR (qRT-PCR) were used to identify differentially expressed circRNAs in GC tissues and cell lines. circCUL2 knockdown and overexpression were performed to indicate the functional role of circCUL2 in vitro and in vivo. The expression and regulation of circCUL2, miR-142-3p and ROCK2 were evaluated using fluorescence in situ hybridization (FISH), dual-luciferase assays, RNA pull-down assays, RNA immunoprecipitation (RIP) and rescue experiments. Furthermore, the regulation of cisplatin sensitivity and autophagy by circCUL2/miR-142-3p/ROCK2 was demonstrated by cellular apoptosis assays, western blot, immunofluorescence and transmission electron microscopy analyses. Results: The level of circCUL2, which is stable and cytoplasmically localized, was significantly reduced in GC tissues and cells. Overexpressed circCUL2 inhibited malignant transformation in vitro and tumorigenicity in vivo. In the AGS and SGC-7901 cell lines, circCUL2 sponged miR-142-3p to regulate ROCK2, thus modulating tumor progression. Furthermore, in the AGS/DDP and SGC-7901/DDP cell lines, circCUL2 regulated cisplatin sensitivity through miR-142-3p/ROCK2-mediated autophagy activation. Conclusion: circCUL2 may function as a tumor suppressor and regulator of cisplatin sensitivity through miR-142-3p/ROCK2mediated autophagy activation, which could be a key mechanism and therapeutic target for GC. Keywords: circCUL2, miR-142-3p, ROCK2, Gastric cancer, Cisplatin resistance, Autophagy
* Correspondence: [email protected] † Lei Peng, Huaiming Sang, Shuchun Wei and Yuanyuan Li contributed equally to this work. 1 Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons li
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