circCUL2 regulates gastric cancer malignant transformation and cisplatin resistance by modulating autophagy activation via miR-142-3p/ROCK2.
circCUL2 regulates gastric cancer malignant transformation and cisplatin resistance by modulating autophagy activation via miR-142-3p/ROCK2.
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circCUL2通过miR-142-3p/ROCK2调节自噬激活调节胃癌恶性转化和顺铂耐药
DOI：
10.1186/s12943-020-01270-x
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发表时间：
2020-11-05
期刊：
影响因子：
37.3
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Peng L;Sang H;Wei S;Li Y;Jin D;Zhu X;Li X;Dang Y;Zhang G
研究背景环状RNA（Circular RNA，circRNA）是一类非编码RNA（noncoding RNA，ncRNA），通过与miRNA结合来调节基因表达，并参与多种病理过程。方法应用circRNA微阵列技术和实时荧光定量PCR（qRT-PCR）技术，对胃癌组织和胃癌细胞株中circCUL 2的表达及生物学功能进行研究。进行circCUL 2敲低和过表达以表明circCUL 2在体外和体内的功能作用。使用荧光原位杂交（FISH）、双荧光素酶测定、RNA下拉测定、RNA免疫沉淀（RIP）和拯救实验来评估circCUL 2、miR-142- 3 p和ROCK 2的表达和调节。此外，通过细胞凋亡检测、Western blot、免疫荧光和透射电镜分析，证实了circCUL 2/miR-142- 3 p/ROCK 2对顺铂敏感性和自噬的调节作用。过表达的circCUL 2抑制体外恶性转化和体内致瘤性。在AGS和SGC-7901细胞系中，circCUL 2吸收miR-142- 3 p以调节ROCK 2，从而调节肿瘤进展。结论circCUL 2可能通过miR-142 - 3 p/ROCK 2介导的自噬激活发挥肿瘤抑制和顺铂敏感性调节作用，可能是胃癌发生的重要机制和治疗靶点。
BackgroundCircular 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.MethodscircRNA 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.ResultsThe 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.ConclusioncircCUL2 may function as a tumor suppressor and regulator of cisplatin sensitivity through miR-142-3p/ROCK2-mediated autophagy activation, which could be a key mechanism and therapeutic target for GC.
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DOI：
10.1186/s13046-018-0762-y
发表时间：
2018-04-27
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Liu X;Feng C;Liu J;Cao L;Xiang G;Liu F;Wang S;Jiao J;Niu Y
通讯作者：
Niu Y
新型环状RNA circFN1通过海绵miR-182-5p增强胃癌顺铂耐药性
影响因子：
4
作者：
Huang, Xiao-xu;Zhang, Qiang;Xu, Li
通讯作者：
Xu, Li
影响因子：
13.5
作者：
Han, Dan;Li, Jiangxue;Cao, Xuetao
通讯作者：
Cao, Xuetao
影响因子：
3
作者：
Jiang, F.;Shen, X. B.
通讯作者：
Shen, X. B.
影响因子：
4.6
作者：
Li, Manhua;Ke, Jing;Huang, Hua
通讯作者：
Huang, Hua