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m6A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression

Liu, Hua ; Jiang, Yifan ; Lu, Jiahua ; Peng, Chuanhui ; Ling, Zhenan ; Chen, Yunhao ; Chen, Diyu ; Tong, Rongliang ; Zheng, Shusen ; Wu, Jian

Epigenetics, 2023, Vol.18 (1)

Taylor & Francis

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  • Título:
    m6A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression
  • Autor: Liu, Hua ; Jiang, Yifan ; Lu, Jiahua ; Peng, Chuanhui ; Ling, Zhenan ; Chen, Yunhao ; Chen, Diyu ; Tong, Rongliang ; Zheng, Shusen ; Wu, Jian
  • Assuntos: Circ-CCT3 ; FLT1 ; Hepatocellular carcinoma ; MiR-378a-3p ; N6-methyladenosine
  • É parte de: Epigenetics, 2023, Vol.18 (1)
  • Descrição: 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 2 A) 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.
  • Editor: Taylor & Francis
  • Idioma: Inglês

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