m(6)A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression.
m(6)A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression.
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DOI：
10.1080/15592294.2023.2204772
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发表时间：
2023-12
期刊：
影响因子：
3.7
通讯作者：
Wu, Jian
中科院分区：
文献类型：
--
作者：
Liu, Hua;Jiang, Yifan;Lu, Jiahua;Peng, Chuanhui;Ling, Zhenan;Chen, Yunhao;Chen, Diyu;Tong, Rongliang;Zheng, Shusen;Wu, Jian
背景：环状RNA（circRNA）在肿瘤进展中起着关键作用。Circ-CCT 3是一种特别丰富的circRNA，被认为与肿瘤发生有关。然而，circ-CCT 3在肝细胞癌中的作用仍然难以捉摸。方法：在这里，circ-CCT 3（来自CCT 3基因的外显子3，4和5的circRNA，hsa_circ_0004680）通过circRNA微阵列鉴定并通过qRT-PCR验证。进行RNA免疫沉淀（RIP）以确认ALKBH 5沿着有胃L3和circ-CCT 3之间的结合。甲基化RNA免疫沉淀（MeRIP）用于检测circ-CCT 3的N6-甲基腺苷（m 2A）水平。进行CircRNA体内沉淀、荧光素酶报告基因测定、生物素偶联的microRNA捕获和荧光原位杂交以评估circ-CCT 3和miR-378 a-3 p之间的相互作用。结果：circ-CCT 3在肝癌组织中高表达，提示肝癌预后不良。Circ-CCT 3表达是HCC患者总生存期的独立危险因素。circ-CCT 3基因的敲低可抑制肝癌细胞的增殖、侵袭和迁移，抑制HUVEC的血管生成。在机制上，ALKBH 5和胃L3可以结合和调节circ-CCT 3的mRNA修饰。结论：Circ-CCT 3在HCC中表达上调，并通过miR-378 a-3 p-FLT 1轴促进肝癌的发生发展。还发现circ-CCT 3处于由ALKBH 5和胃L3介导的mRNA修饰下。我们的研究突出了circ-CCT 3作为HCC治疗的潜在治疗靶点，这为circRNA在HCC进展中的机制提供了新的理解。
Background: Circular RNA (circRNA) plays a critical role in tumour progression. Circ-CCT3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, the role of circ-CCT3 in hepatocellular carcinoma remains elusive.Methods: Here, circ-CCT3 (a circRNA derived from exons 3, 4 and 5 of the CCT3 gene, hsa_circ_0004680) was identified by circRNA microarray and validated by qRT-PCR. RNA immunoprecipitation (RIP) was performed to confirm the binding between ALKBH5 along with METTL3 and circ-CCT3. Methylated RNA Immunoprecipitation (MeRIP) was used to detect the N6-methyladenosine (m 2A) levels of circ-CCT3. CircRNAs in vivo precipitation, luciferase reporter assay, biotin-coupled microRNA capture, and fluorescence in situ hybridization were conducted to assess the interaction between circ-CCT3 and miR-378a-3p. The functions of circ-CCT3 in HCC were evaluated both in vitro and in vivo.Results: We demonstrated that circ-CCT3 was highly expressed in HCC which indicated the poor prognosis. Circ-CCT3 expression served as an independent risk factor for overall survival in patients with HCC. Knocking-down of circ-CCT3 inhibited the proliferation, invasion and migration of HCC cells, and angiogenesis of HUVEC. Mechanistically, ALKBH5 and METTL3 could bind and regulate m A-modification of circ-CCT3. Further, circ-CCT3 upregulated the expression of FLT-1 by sponging miR-378a-3p.Conclusions: Circ-CCT3 was significantly up-regulated in HCC and promoted liver cancer development via miR-378a-3p-FLT1 axis. It was also found that circ-CCT3 was under m A-modification mediated by ALKBH5 and METTL3. Our study highlights circ-CCT3 as a potential therapeutic target of HCC treatment, which provides a novel understanding on mechanisms of circRNAs in HCC progression.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/j.omtn.2022.01.013
发表时间：
2022-03-08
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Huang X;Guo H;Wang L;Yang L;Shao Z;Zhang W
通讯作者：
Zhang W
影响因子：
5.2
作者：
Han TS;Hur K;Cho HS;Ban HS
通讯作者：
Ban HS
影响因子：
28.5
作者：
Dong Y;He D;Peng Z;Peng W;Shi W;Wang J;Li B;Zhang C;Duan C
通讯作者：
Duan C
影响因子：
13.5
作者：
Han, Dan;Li, Jiangxue;Cao, Xuetao
通讯作者：
Cao, Xuetao