circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis

Liu, Fei; Yang, Shi Yu; Zheng, Yang; Gu, Lina; Meng, Lingjiao; Li, Ziyi; Dong, Yi; Wei, Zishuan; Chen, Geng; Sang, Meixiang

doi:10.3390/cancers14235862

Cited by 5 publications

(4 citation statements)

References 34 publications

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“…As for the biological function of circRNF10 in BC, we discovered that circRNF10 inhibited BC proliferation and progression. These findings were consistent with previous studies, which showed that circRNF10 inhibited tumorigenicity by sponging miR-934 and miR-942-5p in BC [ 15 , 16 ]. Considering the inhibitory effect of circRNF10 on BC, it raised the possibility that circRNF10 might become an agent for BC treatment.…”

Section: Discussionsupporting

confidence: 93%

“…As for the cytoplasmic circRNAs, they mostly acted as a sponge of miRNAs [ 34 ] and decoys of proteins [ 35 ]. Previous studies have explored the role of circRNF10 as an miRNA sponge [ 15 , 16 ]. Differing from these studies, we focused on the potential of circRNF10 in binding proteins and discovered a novel role in which it could bind to DHX15 in BC by interacting with the RecA2 domain.…”

Section: Discussionmentioning

confidence: 99%

“…An increasing body of evidence suggests that circRNAs have important biological functions in BC progression [ 12 – 14 ]. Previous studies have indicated that circRNF10 could act as the sponge of miR-934 and miR-942-5p [ 15 , 16 ]. Whether it could interact with proteins is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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CircRNF10-DHX15 interaction suppressed breast cancer progression by antagonizing DHX15-NF-κB p65 positive feedback loop

Zheng

Wang

et al. 2023

Cell Mol Biol Lett

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Background Breast cancer (BC) is a common threat to women. The continuous activation of nuclear factor kappa B (NF-κB) signaling pathway contributes to the development of BC. This study aimed to investigate the role of a circular RNA (circRNF10) in BC progression and regulating NF-κB signaling pathway. Methods Bioinformatics analysis, RT-qPCR, subcellular fractionation, FISH, RNase R treatment, and actinomycin D assay were used to explore the expression and characteristics of circRNF10 in BC. The biological functions of circRNF10 in BC were analyzed by MTT assay, colony formation assay, wound healing assay, and Transwell assay. RNA pulldown and RIP assay were used to identify the interaction between circRNF10 and DEAH (Asp-Glu-Ala-His) box helicase 15 (DHX15). The impact of circRNF10-DHX15 interaction on NF-κB signaling pathway was explored by western blot, IF, and co-IP. Furthermore, dual-luciferase reporter assay, ChIP, and EMSA were performed to assess the effect of NF-κB p65 on DHX15 transcription. Results CircRNF10 was downregulated in BC, and lower expression of circRNF10 was related to poor prognosis of patients with BC. CircRNF10 inhibited the proliferation and migration of BC. Mechanically, circRNF10-DHX15 interaction sequestered DHX15 from NF-κB p65, thereby inhibiting the activation of NF-κB signaling pathway. On the other hand, NF-κB p65 enhanced DHX15 transcription by binding to the promoter of DHX15. Altogether, circRNF10 impaired the DHX15-NF-κB p65 positive feedback loop and suppressed the progression of BC. Conclusion CircRNF10-DHX15 interaction suppressed the DHX15-NF-κB p65 positive feedback loop, thereby inhibiting BC progression. These findings provide new insights in the continuous activation of NF-κB signaling pathway and raised potential therapeutic approach for BC treatment.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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CircRNF10-DHX15 interaction suppressed breast cancer progression by antagonizing DHX15-NF-κB p65 positive feedback loop

Zheng

Wang

et al. 2023

Cell Mol Biol Lett

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“…According to growing data, the majority of circRNAs have a role in the development of BC by acting as miRNA sponges. CircRNF10, for instance, may prevent the progression of BC by sponging miR-934 and controlling the PTEN/PI3K/AKT axis [ 14 ]. Similarly, circ-TRIO could sponge miR-432-5p to regulate the expression of Coiled-Coil Domain Containing 58 (CCDC58) and participate in triple negative BC tumorigenesis [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression

Ju,

Zhou,

et al. 2023

Cell Death Dis

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Breast cancer (BC) is one of the most frequent cancer-related deaths in women worldwide. Studies have shown the potential impact of circRNAs in multiple human tumorigeneses. Research on the vital signaling pathways and therapeutic targets of circRNAs is indispensable. Here, we aimed to investigate the clinical implications and underlying mechanisms of circ_0042881 in BC. RT-qPCR validated circ_0042881 was notably elevated in BC tissues and plasma, and closely associated with BC clinicopathological features. Functionally, circ_0042881 significantly accelerated the proliferation, migration, and invasion of BC cells in vitro and tumor growth and metastasis in vivo. Mechanistically, circ_0042881 promoted BC progression by sponging miR-217 to relieve its inhibition effect in son of sevenless 1 (SOS1), which further activated RAS protein and initiated downstream signaling cascades, including MEK/ERK pathway and PI3K/AKT pathway. We also demonstrated that treatment of BAY-293, an inhibitor of SOS1 and RAS interaction, attenuated BC progression induced by circ_0042881 overexpression. Furthermore, Eukaryotic initiation factor 4A-III (EIF4A3) could facilitate circ_0042881 circularization. Altogether, we proposed a novel signaling network in which circ_0042881, induced by EIF4A3, influences the process of BC tumorigenesis and metastasis by miR-217/SOS1 axis.

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The investigation of circRNA profiling reveals the regulatory role of the hsa_circ_0000375/miR-7706 pathway in breast cancer

Wang,

Liu,

Xue

et al. 2023

Mol Biol Rep

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Circular RNAs (circRNAs) take an effect on tumorigenesis and progression. However, circRNAs have not been systematically identi ed in breast cancer (BC) as crucial regulators in multitudinous biological processes. This study is conducted to explore novel circRNAs in BC and the corresponding mechanisms of their action. The circRNA expression pro le and RNA-sequencing data about BC were respectively downloaded from public database. Differentially expressed circRNAs, miRNA, and mRNA were identi ed by fold change ltering. The competing endogenous RNAs (ceRNAs) network was established based on the relationship between circular RNAs, miRNAs and mRNAs. GO and KEGG enrichment analysis of the overlapped genes were carried out to predict the potential functions and mechanisms of circRNAs in BC.The CytoHubba plugin in Cytoscape was applied to identify the hub genes from the PPI regulatory network. Kaplan-Meier plotter was used to perform survival analysis of these hub genes further. Realtime PCR was performed to test the expression of circRNA in breast cancer tissues. Cell function studies including transwell analysis and CCK-8 analysis were used to investigate circRNAs' biological functions. We identi ed a total of 7 differentially expressed circRNAs. After the intersection between the predicted target miRNA and the down-regulated differential miRNAs (DEmiRNAs), circRNA-miRNA interactions involving 3 circRNAs (hsa_circ_0028899, hsa_circ_0000375, hsa_circ_0000376) and 4 miRNAs (hsa-miR-934, hsa-miR-7706, hsa-miR-4443, hsa-miR-4784) were identi ed. Venn diagram was utilized to intersect the predicted target genes of the 4 miRNAs and the down-regulated differential genes in BC, and 149 overlapped genes were screened out ulteriorly. Additionally, we built a protein-protein interaction (PPI) network and selected six hub genes. Moreover, the survival data of BC patients suggested that low expression of ADIPOQ, LPL and LEP were signi cantly correlated with poor prognosis. Results from realtime PCR indicated that has_circ_0000375 was signi cantly down-regulated in breast cancer tissues.Functional in vitro experiments showed that over-expression of hsa_circ_0000375 can restrain proliferation, migration and invasion abilities of breast cancer cells. Further veri cation indicated that hsa_circ_0000375 exerted its anti-oncogene effect via sponge of miR-7706. This study constructed and analyzed a circRNA-associated ceRNA regulatory network and uncovered that hsa_circ_0000375 exerted its anti-oncogene effect via sponge of miR-7706.

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circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis

Cited by 5 publications

References 34 publications

CircRNF10-DHX15 interaction suppressed breast cancer progression by antagonizing DHX15-NF-κB p65 positive feedback loop

CircRNF10-DHX15 interaction suppressed breast cancer progression by antagonizing DHX15-NF-κB p65 positive feedback loop

EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression

The investigation of circRNA profiling reveals the regulatory role of the hsa_circ_0000375/miR-7706 pathway in breast cancer

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