CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress

Li, Qidong; Wang, Yichun; Wu, Shuang; Zhou, Zhong; Ding, Xiaofeng; Shi, Ronghua; Thorne, Rick F.; Zhang, Xu Dong; Hu, Wanglai; Wu, Mian

doi:10.1016/j.cmet.2019.05.009

Cited by 236 publications

(182 citation statements)

References 87 publications

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“…The reports about circRNAs modulating the pathogenesis of malignant tumors via targeting of RBPs are limited. Circ-ACC1 has been demonstrated to directly bind to AMPK β and γ subunits and facilitate AMPK holoenzyme assembly, stability, and activity [48]. CircRHOT1 was found to promote hepatocellular carcinoma (HCC) growth through the recruitment of TIP60 to the promoter of NR2F6 and initiating NR2F6 transcription [49].…”

Section: Discussionmentioning

confidence: 99%

The Circular RNA circZFR Phosphorylates Rb Promoting Cervical Cancer Progression by Regulating the SSBP1/CDK2/cyclin E1 Complex

Zhou

Yang

Wang³

et al. 2020

Preprint

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Background: As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods: We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change >2, and P <0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR.Results: Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion: Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.

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Section: Discussionmentioning

confidence: 99%

The Circular RNA circZFR Phosphorylates Rb Promoting Cervical Cancer Progression by Regulating the SSBP1/CDK2/cyclin E1 Complex

Zhou

Yang

Wang³

et al. 2020

Preprint

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“…Since hsa_circ_0002346 was the first reported isoform of circRNAs arise from the CRIM1 gene, we termed it as "circCRIM1", as previously described ( Fig. 1b) [23][24][25].…”

Section: Circrna Crim1 Is Upregulated In Npc Patients With Distant Mementioning

confidence: 99%

“…1g, P < 0.05). To prove that these were on-target effects resulting from circCRIM1 knockdown, we performed sequence alignment analyses and constructed a circCRIM1 overexpression vector resistant to siRNAs with mutated back-spliced junction (circCRIM1-si-mut), according to previous instructions [24,25,27]. Although there were 15 circRNA isoforms derived from CRIM1 gene in S18 cell line, only the isoform concerned in our study (circCRIM1/hsa_circ_0002346) contained completely complementary backsplice sequences to si-circCRIM1-1 and si-circCRIM1-2 (Additional file 1: Figure S3-S4).…”

Section: Circcrim1 Promotes Npc Cell Migration Invasion and Emt In Vmentioning

confidence: 99%

Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1

et al. 2020

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Background: Circular RNAs (circRNAs), a new type of noncoding RNA (ncRNA), have been identified as significant gene expression regulators and are involved in cancer progression. However, the roles of circRNAs in nasopharyngeal carcinoma (NPC) remain largely unknown. Methods: Here, the expression profile of circRNAs in a pair of NPC cell lines with different metastatic abilities (S18 and S26 cells) was analyzed by RNA-sequencing. Quantitative reverse transcription PCR was used to detect the expression level of circCRIM1 in NPC cells and tissues. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circCRIM1 on NPC metastasis and EMT. Mechanistically, RNA immunoprecipitation, luciferase reporter assay, pull-down assay with biotinylated miRNA, fluorescent in situ hybridization were performed to confirm the interaction between circCRIM1 and miR-422a in NPC. The clinical value of circCRIM1 was evaluated in NPC metastasis and chemosensitivity. Results: We identified that circCRIM1 was upregulated in highly metastatic NPC cells. CircCRIM1 was also overexpressed in NPC tissues with distant metastasis, and its overexpression promoted NPC cell metastasis and EMT. Mechanistically, circCRIM1 competitively bound to miR-422a and prevented the suppressive effects of miR-422a on its target gene FOXQ1, which finally led to NPC metastasis, EMT and docetaxel chemoresistance. Furthermore, high circCRIM1 expression was associated with unfavorable survival in NPC patients. We established a prognostic model based on circCRIM1 expression and N stage that effectively predicted the risk of distant metastasis and treatment response to docetaxel-containing induction chemotherapy in NPC patients. Conclusions: Our findings reveal the critical role of circCRIM1 specifically in promoting NPC metastasis and chemoresistance via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for prognosis and treatment resistance in NPC patients.

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“…Numerous researchers have proved that circular RNAs can compete with mRNAs for target binding sites of miRNAs to in turn regulate the expression of mRNAs [15,23]. Furthermore, in recent years, the protein-binding function and the potentiality translating into short-peptide has attracted increasing attention [24,25], which may…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of circRNAs from steatotic livers after ischemia and reperfusion injury by next generation RNA sequencing

Zheng

Wang

et al. 2020

Preprint

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Background Global organ shortage has enabled the permission of fatty livers for transplantation purpose, taking the risk of graft dysfunction related to the rapider ischemia/reperfusion injury (IRI) progress. Increasing evidence supports the role of circular RNAs as essential regulators of this progress. However, data about circular RNAs in ischemia and reperfusion injured steatotic livers are practically nonexistent. Methods In the present study, high-fat diet (HFD)-fed mice model was used to generate hepatic steatosis mice. RNA-sequencing was performed on IRI model or sham liver tissues both in HFD-fed mice to screen the significant differentially expressed circular RNAs. GO and KEGG analysis were applied to figure out the potential function of these screened circular RNAs. Results From this, we successfully found the expression of some circular RNAs were significantly altered in IRI livers after HFD-fed mouse models. To further validate sequencing data, one up-regulated circRNA and four down-regulated circular RNAs were examined in steatotic mice livers after IRI. The RNase R digestion experiment exhibited these circRNAs possessed high stability compared with linear RNAs and sequence alignment of their junction positions provided identical sequences by sanger sequencing following gel electrophoresis, demonstrating the circularity of these circular RNAs. The expression of four stable circRNAs undigested by RNase R were further validated by quantitative PCR. Conclusion In summary, this study reveals that circular RNAs emerge as novel and potentially efficient targets which involve in more severe damage of steatotic livers to IRI.

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CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress

Cited by 236 publications

References 87 publications

The Circular RNA circZFR Phosphorylates Rb Promoting Cervical Cancer Progression by Regulating the SSBP1/CDK2/cyclin E1 Complex

The Circular RNA circZFR Phosphorylates Rb Promoting Cervical Cancer Progression by Regulating the SSBP1/CDK2/cyclin E1 Complex

Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1

Comprehensive analysis of circRNAs from steatotic livers after ischemia and reperfusion injury by next generation RNA sequencing

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