Dataset Information

M⁶A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression.

ABSTRACT: 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.

SUBMITTER: Liu H

PROVIDER: S-EPMC10128399 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Liu Hua H Jiang Yifan Y Lu Jiahua J Peng Chuanhui C Ling Zhenan Z Chen Yunhao Y Chen Diyu D Tong Rongliang R Zheng Shusen S Wu Jian J

Epigenetics 20231201 1

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 A ...[more]

PMID: 37092305

Similar Datasets

Project description:BackgroundGastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of noncoding RNA, have been proven to act as miRNA sponges that can widely regulate various cancers. By this mechanism, circRNA can regulate tumors at the genetic level by releasing miRNA from inhibiting its target genes. The WNT2/β-Catenin regulatory pathway is one of the canonical signaling pathways in tumors. It can not only promote the development of tumors but also provide energy for tumor growth through cell metabolism (such as glutamine metabolism).MethodsThrough RNA sequencing, we found that hsa_circ_0008259 (circLMO7) was highly expressed in GC tissues. After verifying the circular characteristics of circLMO7, we determined the downstream miRNA (miR-30a-3p) of circLMO7 by RNA pull-down and luciferase reporter assays. We verified the effect of circLMO7 and miR-30a-3p on GC cells through a series of functional experiments, including colony formation, 5-ethynyl-2'-deoxyuridine and Transwell assays. Through Western blot and immunofluorescence analyses, we found that WNT2 was the downstream target gene of miR-30a-3p and further confirmed that the circLMO7-miR-30a-3p-WNT2 axis could promote the development of GC. In addition, measurement of related metabolites confirmed that this axis could also provide energy for the growth of GC cells through glutamine metabolism. We found that circLMO7 could promote the growth and metastasis of GC in vivo by the establishment of nude mouse models. Finally, we also demonstrated that HNRNPL could bind to the flanking introns of the circLMO7 exons to promote circLMO7 cyclization.ResultsCircLMO7 acted as a miR-30a-3p sponge affecting the WNT2/β-Catenin pathway to promote the proliferation, migration and invasion of GC cells. Moreover, animal results also showed that circLMO7 could promote GC growth and metastasis in vivo. CircLMO7 could also affect the glutamine metabolism of GC cells through the WNT2/β-Catenin pathway to promote its malignant biological function. In addition, we proved that HNRNPL could promote the self-cyclization of circLMO7.ConclusionsCircLMO7 promotes the development of GC by releasing the inhibitory effect of miR-30a-3p on its target gene WNT2.

Dataset Information

M⁶A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression.

Publications

m<sup>6</sup>A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

M6A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression.

Publications

m<sup>6</sup>A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M⁶A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression.