A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking

Harrison, Emily B.; Porrello, Alessandro; Bowman, Brittany M.; Belanger, Adam R.; Yacovone, Gabriella; Azam, Salma H.; Windham, Ian A.; Ghosh, Subrata; Wang, Menglin; Mckenzie, Nicholas; Waugh, Trent A.; Swearingen, Amanda E.D. Van; Cohen, Stephanie M.; Allen, Devon G.; Goodwin, Tyler J.; Mascenik, Teresa; Bear, James E.; Randell, Scott H.; Massion, Pierre P.; Major, Michael B.; Huang, Leaf; Pecot, Chad V.

doi:10.1158/0008-5472.can-20-1162

Cited by 25 publications

(17 citation statements)

References 46 publications

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“…Unlike these two kinds of ncRNAs, circRNAs have emerged as more reliable and promising tumor biomarkers owing to their exceptionally stable structure. Advanced genome sequencing techniques have validated the roles of circRNAs in multiple cancers, including hepatocellular carcinoma [29], gastric cancer [30], colorectal cancer [31] and lung squamous cell carcinoma [32]. However, to date, the expression profiles and roles of circRNAs in OS are not well understood.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ_001422 promotes the progression and metastasis of osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt axis

Yang

et al. 2021

J Exp Clin Cancer Res

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Background Circular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied. Methods Bioinformatic analysis and high-throughput RNA sequencing tools were employed to identify differentially expressed circRNAs between OS and adjacent noncancerous tissues. The expression level of circ_001422 in clinical specimens and cell lines was measured using qRT-PCR. The association of circ_001422 expression with the clinicopathologic features of 55 recruited patients with OS was analyzed. Loss- and gain-of-function experiments were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescence in situ hybridization, bioinformatics database analysis, RNA pulldown assays, dual-luciferase reporter assays, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNA regulatory network controlled by circ_001422. Results We characterized a novel and abundant circRNA, circ_001422, that promoted OS progression. Circ_001422 expression was dramatically increased in OS cell lines and tissues compared with noncancerous samples. Higher circ_001422 expression correlated with more advanced clinical stage, larger tumor size, higher incidence of distant metastases and poorer overall survival in OS patients. Circ_001422 knockdown markedly repressed the proliferation and metastasis and promoted the apoptosis of OS cells in vivo and in vitro, whereas circ_001422 overexpression exerted the opposite effects. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated FGF2 expression while also initiating PI3K/Akt signaling. These events enhanced the malignant characteristics of OS cells. Conclusions Circ_001422 accelerates OS tumorigenesis and metastasis by modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 can be therapeutically targeted to treat OS.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circ_001422 promotes the progression and metastasis of osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt axis

Yang

et al. 2021

J Exp Clin Cancer Res

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show abstract

“…Unlike these two kinds of ncRNAs, circRNAs have emerged as more reliable and promising tumor biomarkers owing to their exceptionally stable structure. Advanced genome sequencing techniques have validated the roles of circRNAs in multiple cancer types including hepatocellular carcinoma [24], gastric cancer [25], colorectal cancer [26] and lung squamous carcinoma [27]. However, to date, the expression pro le and role of circRNAs in OS are not well understood.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ_001422 Promotes Progression and Metastasis of Osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt Axis

Yang

Ge³

et al. 2021

Preprint

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BackgroundCircular RNAs (circRNAs) are involved in diverse processes that drive cancer development. Nevertheless, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied.MethodsBioinformatics analysis and high-throughput RNA sequencing tools were employed to determine differentially expressed circRNAs between OS and adjacent healthy tissues. The expression levels of circ_001422 in clinical specimens and cell lines were measured using qRT-PCR. A total of 55 OS patients were recruited to analyze the association of circ_001422 expression with clinicopathologic features. Loss- and gain-of-function tests were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescent in situ hybridization, bioinformatics databases, RNA pull-down assay, dual-luciferase reporter assay, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNAs regulatory network dominated by circ_001422.ResultsWe characterized a novel and abundant circRNA, circ_001422, which promoted the progression of OS. Circ_001422 expression was dramatically higher in OS cell lines and tissues relative to normal samples. Increased circ_001422 correlated with more advanced clinical stage, larger tumor size, more distant metastases and poorer overall survival of OS patients. Knockdown of circ_001422 markedly repressed proliferation and metastasis and promoted apoptosis of OS cells in vivo and in vitro, whereas overexpression of circ_001422 exerted an opposite effect. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated the expression of FGF2 while also initiating the PI3K/Akt signaling pathway. These events enhanced the malignant characteristics of OS cells.ConclusionsCirc_001422 accelerates OS tumorigenesis and metastasis through modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 could be therapeutically targeted to treat OS patients.

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“…Although this study found several miRNAs and mRNAs that may be related to NP through the public datasets, and analyzed the pathways that may participate in the pathological mechanism of NP through GO and KEGG pathway analysis, our research still has some limitations. Circular RNAs (circRNAs) and lncRNAs are non-coding RNA molecules that have recently been reported to regulate the function of miRNAs and affect a variety of complex human diseases (Fan et al 2020 ; Harrison et al 2020 ; Li et al 2020b ). Although there have been some studies on the circRNA regulation in NP (Li et al 2020a ; Wei et al 2020 ; Zhang et al 2020 ), the present public databases still do not include the circRNA expression data of NP.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of the MicroRNA-Metabolic Gene Regulatory Network in Neuropathic Pain and Prediction of Corresponding Potential Therapeutics

et al. 2021

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Neuropathic pain (NP) involves metabolic processes that are regulated by metabolic genes and their non-coding regulator genes such as microRNAs (miRNAs). Here, we aimed at exploring the key miRNA signatures regulating metabolic genes involved in NP pathogenesis. We downloaded NP-related data from public databases and identified differentially expressed microRNAs (miRNAs) and mRNAs through differential gene expression analysis. The miRNA target prediction was performed, and integration with the differentially expressed metabolic genes (DEMGs) was used for constructing the miRNA-DEMG network. Subsequently, functional enrichment analysis and protein–protein interaction (PPI) analysis were performed to explore the role of DEMGs in the regulatory network. The drug prediction was performed based on the DEMGs in the miRNA-DEMG network. A total of 8251 differentially expressed mRNAs (4193 upregulated and 4058 downregulated), and 959 differentially expressed miRNAs (455 upregulated and 504 downregulated) were identified. Moreover, after target gene prediction, a miRNA-DEMG network composed of 22 miRNAs and 113 mRNAs was constructed. The network was constituted of 135 nodes and 236 edges. We found that DEMGs in the network were mainly enriched in metabolic pathways and metabolic processes. A total of 1200 drugs were predicted as potential therapeutics for NP based on the differentially expressed genes, while 170 drugs were predicted for the DEMGs in the miRNA-DEMG network. Conclusively, our study predicted drugs that may be effective against the metabolic changes induced by miRNA dysregulation in NP. This information will help further reveal the pathological mechanism of NP and provide more treatment options for NP patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12031-021-01911-w.

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A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1-Mediated Regulation of Golgi Trafficking

Cited by 25 publications

References 46 publications

Circular RNA circ_001422 promotes the progression and metastasis of osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt axis

Circular RNA circ_001422 promotes the progression and metastasis of osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt axis

Circular RNA circ_001422 Promotes Progression and Metastasis of Osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt Axis

Bioinformatics Analysis of the MicroRNA-Metabolic Gene Regulatory Network in Neuropathic Pain and Prediction of Corresponding Potential Therapeutics

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