Dataset Information

CircRNF13, a novel N⁶-methyladenosine-modified circular RNA, enhances radioresistance in cervical cancer by increasing CXCL1 mRNA stability.

ABSTRACT:

Background

Circular RNAs (circRNAs) and N⁶-methyladenosine (m⁶A) have been shown to play an increasingly critical role in the development of different cancers. However, there is limited evidence on how circRNAs and m⁶A interact to affect the radiosensitivity of cervical cancer (CC). This study provides a mechanistic understanding of the novel m⁶A-regulated circRNF13 in enhancing radioresistance in CC.

Methods

Differentially expressed circRNAs were identified from radiosensitive and radioresistant CC tissues. Meanwhile, these circRNAs were subjected to methylated RNA immunoprecipitation (Me-RIP). Finally, the effects of these circRNAs on radiosensitivity were characterized.

Results

CircRNF13 was poorly expressed in CC patients that were sensitive to concurrent radiochemotherapy. Experiments conducted both in vitro and in vivo confirmed that the knockdown of circRNF13 potentiated the radiosensitivity of CC cells. Further mechanistic studies revealed that METTL3/YTHDF2 promoted the degradation of circRNF13 and subsequently affected the stability of CXC motif chemokine ligand 1 (CXCL1), ultimately enhancing the radiosensitivity of CC cells.

Conclusion

This study identified circRNF13 as a novel m⁶A-modified circRNA and validated the METTL3/YTHDF2/circRNF13/CXCL1 axis as a potential target for CC radiotherapy.

SUBMITTER: Shi J

PROVIDER: S-EPMC10356927 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

circRNF13, a novel N<sup>6</sup>-methyladenosine-modified circular RNA, enhances radioresistance in cervical cancer by increasing CXCL1 mRNA stability.

Shi Junyu J Rui Xiaohui X Han Chunxiao C Wang Chaoping C Xu Lei L Jiang Xiping X

Cell death discovery 20230720 1

<h4>Background</h4>Circular RNAs (circRNAs) and N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) have been shown to play an increasingly critical role in the development of different cancers. However, there is limited evidence on how circRNAs and m<sup>6</sup>A interact to affect the radiosensitivity of cervical cancer (CC). This study provides a mechanistic understanding of the novel m<sup>6</sup>A-regulated circRNF13 in enhancing radioresistance in CC.<h4>Methods</h4>Differentially expressed cir ...[more]

PMID: 37468464

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Project description:BackgroundCircular RNAs (circRNAs) are widely expressed in human cells and are closely associated with cancer development. However, they have rarely been investigated in the context of nasopharyngeal carcinoma (NPC).MethodsWe screened a new circRNA, circRNF13, in NPC cells using next-generation sequencing of mRNA. Reverse transcription polymerase chain reaction and RNA fluorescence in situ hybridization were used to detect circRNF13 expression in 12 non-tumor nasopharyngeal epithelial (NPE) tissues and 36 NPC samples. Cell proliferation was detected using MTT and flow cytometry assays, and colony formation capability was detected using colony formation assays. Cell migration and invasion were analyzed using wound-healing and Transwell assays, respectively. Cell glycolysis was analyzed using the Seahorse glycolytic stress test. Glucose transporter type 1 (GLUT1) ubiquitination and SUMOylation modifications were analyzed using co-immunoprecipitation and western blotting. CircRNF13 and Small Ubiquitin-like Modifier 2 (SUMO2) interactions were analyzed using RNA pull-down and luciferase reporter assays. Finally, to test whether circRNF13 inhibited NPC proliferation and metastasis in vivo, we used a xenograft nude mouse model generated by means of subcutaneous or tail vein injection.ResultsWe found that circRNF13 was stably expressed at low levels in NPC clinical tissues and NPC cells. In vitro and in vivo experiments showed that circRNF13 inhibited NPC proliferation and metastasis. Moreover, circRNF13 activated the SUMO2 protein by binding to the 3'- Untranslated Region (3'-UTR) of the SUMO2 gene and prolonging the half-life of SUMO2 mRNA. Upregulation of SUMO2 promotes GLUT1 degradation through SUMOylation and ubiquitination of GLUT1, which regulates the AMPK-mTOR pathway by inhibiting glycolysis, ultimately resulting in the proliferation and metastasis of NPC.ConclusionsOur results revealed that a novel circRNF13 plays an important role in the development of NPC through the circRNF13-SUMO2-GLUT1 axis. This study implies that circRNF13 mediates glycolysis in NPC by binding to SUMO2 and provides an important theoretical basis for further elucidating the pathogenesis of NPC and targeted therapy.

Project description:Background: N6-methyladenosine (m6A) is the most prevalent non-cap reversible modification present in messenger RNAs and long non-coding RNAs, and its dysregulation has been linked to multiple cardiovascular diseases, including cardiac hypertrophy and atherosclerosis. Although limited studies have suggested that m6A modification contributes to abdominal aortic aneurysm (AAA) development, the full landscape of m6A regulators that mediate modification patterns has not been revealed. Methods: To distinguish the m6A methylation subtypes in AAA patients, an unsupervised clustering method was carried out, based on the mRNA levels of 17 m6A methylation regulators. Differentially expressed genes were identified by comparing clusters. An m6Ascore model was calculated using principal component analysis and structured to assess the m6A methylation patterns of single samples. Subsequently, the relationship between the m6Ascore and immune cells and the hallmark gene set was analyzed. Finally, pairs of circRNA-m6A regulators and m6A regulators-m6A related genes were used to establish a network. Results: We identified three m6A methylation subtypes in the AAA samples. The m6Acluster A and C were characterized as more immunologically activated because of the higher abundance of immune cells than that in m6Acluster B. The m6Acluster B was less enriched in inflammatory pathways and more prevalent in pathways related to extracellular matrix stability. Subsequently, we divided the individual samples into two groups according to the m6Ascore, which suggested that a high m6Ascore predicted more active inflammatory pathways and higher inflammatory cell infiltration. A network consisting of 9 m6A regulators and 37 circRNAs was constructed. Conclusion: This work highlighted that m6A methylation modification was highly correlated with immune infiltration of AAA, which may promote the progression of AAA. We constructed an individualized m6Ascore model to provide evidence for individualized treatments in the future.

Dataset Information

CircRNF13, a novel N⁶-methyladenosine-modified circular RNA, enhances radioresistance in cervical cancer by increasing CXCL1 mRNA stability.

Background

Methods

Results

Conclusion

Publications

circRNF13, a novel N<sup>6</sup>-methyladenosine-modified circular RNA, enhances radioresistance in cervical cancer by increasing CXCL1 mRNA stability.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

CircRNF13, a novel N6-methyladenosine-modified circular RNA, enhances radioresistance in cervical cancer by increasing CXCL1 mRNA stability.

Background

Methods

Results

Conclusion

Publications

circRNF13, a novel N<sup>6</sup>-methyladenosine-modified circular RNA, enhances radioresistance in cervical cancer by increasing CXCL1 mRNA stability.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

CircRNF13, a novel N⁶-methyladenosine-modified circular RNA, enhances radioresistance in cervical cancer by increasing CXCL1 mRNA stability.