Silencing of circFoxO3 Protects HT22 Cells from Glutamate-Induced Oxidative Injury via Regulating the Mitochondrial Apoptosis Pathway

Lin, Shaopeng; Hu, Jiasong; Wei, Jue-Xian; Ye, Shan; Bu, Jingyi; Xu, Weiqiang; Chen, Shishi; Wu, Yi; Wu, Guohao; Zhu, Lidong; Pan, Lin; Chen, Xiaohui

doi:10.1007/s10571-020-00817-2

Cited by 20 publications

(14 citation statements)

References 29 publications

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“…Furthermore, a circFOXO3 knockdown can overcome ischemia-reperfusion pain and improve heart graft function [11]. It is also known that circFOXO3 is significantly upregulated after glutamate-induced oxidative stress in HT22 cells, and that circFOXO3 contributes to mitochondria-mediated apoptosis [19]. Here, we demonstrated that circFOXO3 tends to be upregulated in CS-exposed lungs and CSE-treated MLE12 cells.…”

Section: Discussionmentioning

confidence: 52%

Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice

Zhou

Yang

et al. 2021

Respir Res

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Background Chronic obstructive pulmonary disease (COPD) remains a prevalent chronic airway inflammatory disease. Circular RNAs (circRNAs) are associated with inflammation regulation; therefore, we examined distinct effects of circRNA FOXO3 (circFOXO3) against pneumonic inflammatory processes in COPD. Methods We first quantified and localized circFOXO3 in mouse lung epithelial cell line MLE12 by quantitative reverse-transcription PCR and in situ hybridization. Next, circFOXO3 was suppressed by therapeutic administration of circFOXO3 knockdown lentivirus in mice exposed to air or cigarette smoke (CS) for 12 weeks, and several hallmarks of COPD were evaluated. Results We noticed that circFOXO3 is upregulated in CS-exposed lungs and cigarette smoke extract (CSE)-treated murine alveolar epithelial cells. Knockdown of circFOXO3 attenuated the release of CXCL1 and IL-6 as well as inflammatory processes in the lungs of CS-exposed mice. In addition, we identified miR-214-3p as a circFOXO3-targeted microRNA. MiR-214-3p overexpression exerted protective effects against pneumonic inflammation after CS exposure. Silencing of circFOXO3 downregulated IKK-β mRNA (miR-214-3p’s target), resulting in the dysfunction of the NF-κB signaling pathway and attenuation of CSE-induced inflammatory-cytokine expression. Conclusions Collectively, these findings reveal a crucial function of circFOXO3 in the pathological remodeling related to CS-induced inflammatory processes. Hence, circFOXO3 might be a good target for the treatment of inflammatory disorders similar to CS-induced lung inflammation.

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Section: Discussionmentioning

confidence: 52%

Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice

Zhou

Yang

et al. 2021

Respir Res

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“…Sun et al (2018) fount that ipatasertib, a novel ATPcompetitive pan-AKT inhibitor, was used in the treatment of colon cancer to inhibit AKT activity, and then FOXO3 was activated, which up-regulated p53 up-regulated modulator of apoptosis (PUMA), leading to PUMA/Bax-dependent endogenous apoptosis, thereby exerting the anticancer effect of ipatasertib. Similarly, Du et al (2017a) found that the overexpression of circFOXO3 inhibited the interaction between FOXO3 and mouse double minute 2 (MDM2), prevented MDM2 from inducing ubiquitination and degradation of FOXO3, thus increasing the activity of FOXO3 and promoting the expression of PUMA to induce apoptosis of cancer cells (Lin et al, 2020; Figure 1C). In addition, the main function of circRNAs in cancers is to influence the post-transcriptional regulation of other genes by acting as miRNA sponge (Figure 1D).…”

Section: The Biological Functions Of Circfoxo3mentioning

confidence: 91%

“…Furthermore, the overexpression of circFOXO3 is also associated with glutamate-induced oxidative damage in HT22 cell line (Hippocampal neurons from mice). Silencing circFOXO3 can protect HT22 cells by reducing the loss of glutamate-induced mitochondrial membrane potential (Lin et al, 2020). In terms of the effect on cell cycle, circFOXO3 forms ternary complex by combining with CDK2 and P21 (Figure 1B).…”

Section: The Biological Functions Of Circfoxo3mentioning

confidence: 99%

The Emerging Roles of circFOXO3 in Cancer

Rao

Sheng

et al. 2021

Front. Cell Dev. Biol.

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Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs which are mainly formed by reverse splicing of precursor mRNAs. They are relatively stable and resistant to RNase R because of their covalently closed structure without 5’ caps or 3’ poly-adenylated tails. CircRNAs are widely expressed in eukaryotic cells and show tissue, timing, and disease specificity. Recent studies have found that circRNAs play an important role in many diseases. In particular, they affect the proliferation, invasion and prognosis of cancer by regulating gene expression. CircRNA Forkhead box O3 (circFOXO3) is a circRNA confirmed to be abnormally expressed in a variety of cancers, including prostate cancer, hepatocellular carcinoma, glioblastoma, bladder cancer, and breast cancer, etc. At present, the feature of circFOXO3 as a molecular sponge is widely studied to promote or inhibit the development of cancers. However, the diverse functions of circFOXO3 have not been fully understood. Hence, it is important to review the roles of circFOXO3 in cancers. This review has summarized and discussed the roles and molecular mechanism of circFOXO3 and its target genes in these cancers, which can help to enrich our understanding to the functions of circRNAs and carry out subsequent researches on circFOXO3.

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“…Moreover, numerous studies have elucidated that circ-Foxo3 could act as a ceRNA with a circular structure to sponge different miRNAs that target upstream modulators, regulating the expression of oncogenes and tumor suppressors (Nitzan et al, 2014). Although previous studies showed that the aberrant expression of circ-Foxo3 was involved in the diagnosis and prognosis of diseases, Lin et al (2020) focused on the Foxo3/Bim EL pathway activated by circ-Foxo3 which inducing mitochondrial-mediated apoptosis, suggesting a potential target of treatment.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Circular RNA Foxo3: A Promising Cancer-Associated Biomarker

Yang

Zhao

et al. 2021

Front. Genet.

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Circular RNAs (circRNAs) are a class of novel non-coding RNAs (ncRNAs). Emerging evidence demonstrates that circRNAs play crucial roles in many biological processes by regulating linear RNA transcription, downstream gene expression and protein or peptide translation. Meanwhile, recent studies have suggested that circRNAs have the potential to be oncogenic or anti-oncogenic and play vital regulatory roles in the initiation and progression of tumors. Circular RNA Forkhead box O3 (circ-Foxo3, hsa_circ_0006404) is encoded by the human FOXO3 gene and is one of the most studied circular RNAs acting as a sponge for potential microRNAs (miRNAs) (Du et al., 2016). Previous studies have reported that circ-Foxo3 is involved in the development and tumorigenesis of a variety of cancers (bladder, gastric, acute lymphocytic leukemia, glioma, etc.). In this review, we summarize the current studies concerning circ-Foxo3 deregulation and the correlative mechanism in various human cancers. We also point out the potential clinical applications of this circRNA as a biomarker for cancer diagnosis and prognosis.

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Silencing of circFoxO3 Protects HT22 Cells from Glutamate-Induced Oxidative Injury via Regulating the Mitochondrial Apoptosis Pathway

Cited by 20 publications

References 29 publications

Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice

Knockdown of circFOXO3 ameliorates cigarette smoke-induced lung injury in mice

The Emerging Roles of circFOXO3 in Cancer

Circular RNA Foxo3: A Promising Cancer-Associated Biomarker

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