The circEPSTI1/mir-942-5p/LTBP2 axis regulates the progression of OSCC in the background of OSF via EMT and the PI3K/Akt/mTOR pathway

Wang, Jie; Jiang, Canhua; Li, Ning; Wang, Fei; Xu, Ying; Shen, Zhengzhong; Yang, Lina; Li, Zaiye; He, Caiyun

doi:10.1038/s41419-020-02851-w

Cited by 103 publications

(91 citation statements)

References 34 publications

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“…As reported previously, circRNAs usually function as ceRNAs in tumorigenesis (25,26). However, only specific miRNAs may be bound to the appropriate binding sites with the given fragment of circRNAs (27).…”

Section: Discussionmentioning

confidence: 78%

circFBXW7 attenuates malignant progression in lung adenocarcinoma by sponging miR-942-5p

Dong¹,

Qiu²,

Xuan³

et al. 2021

Transl Lung Cancer Res

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Background: As a type of non-coding RNA, circular RNAs (circRNAs) are considered to be functional molecules associated with human cancers. An increasing number of circRNAs have been verified in malignant progression in a number of cancers. The circRNA, circFBXW7, has been proven to play an important role in tumor proliferation and metastasis. However, whether circFBXW7 influences progression in lung adenocarcinoma (LUAD) remains unclear. Methods: Quantitative real-time reverse transcriptase PCR (qRT-PCR) was used to verify circFBXW7 in LUAD cell lines and LUAD tissues. Kaplan-Meier analysis was then used to compare the disease-free survival (DFS) and overall survival (OS) of these LUAD patients. The biological function of circFBXW7 was examined by overexpression and knockdown of circFBXW7 using MTT assay, EdU assay, wound-healing assay, and Transwell in vitro assays. To explore the mechanism of the circFBXW7, RNA pull-down assay, dual luciferase reporter assay, and RNA immunoprecipitation (RIP) assay were employed to examine the interaction between circFBXW7 and miR-942-5p. Western blot was used to study the fundamental proteins associated with the epithelial-mesenchymal transition (EMT) pathway. In vivo studies with BALB/c nude mice subcutaneously injected with cells stably overexpressing circFBXW7 were performed to further validate the in vitro results. Results: circFBXW7 was downregulated in LUAD cell lines and tissues, and LUAD patients with lower levels had shorter DFS and OS. The in vitro study showed that circFBXW7 overexpression inhibited proliferation and migration of A549 and HCC2279 cell lines. These results were confirmed by circFBXW7 knockdown, which showed the reverse effect. The in vivo model showed that the circRNA levels influenced the tumor growth. Finally, we determined that circFBXW7 target miRNA-942-5p which regulates the EMT gene BARX2. The modulation of circFBXW7 levels produced significant changes in EMT genes in vitro and in vivo. Conclusions: Our findings showed that circFBXW7 inhibits proliferation and migration by controlling the miR-942-5p/BARX2 axis in LUAD cell lines and its levels correlates with patient survival suggesting that regulating circFBXW7 could have therapeutic value in treating LUAD patients.

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Section: Discussionmentioning

confidence: 78%

circFBXW7 attenuates malignant progression in lung adenocarcinoma by sponging miR-942-5p

Dong¹,

Qiu²,

Xuan³

et al. 2021

Transl Lung Cancer Res

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“…Oral submucous fibrosis (OSMF) is a chronic, progressive, pre-malignant condition mainly related to the consumption of betel nuts ( Singh et al, 2018 ). In recent years, many studies have investigated miRNAs related to OSMF, including miR-21, miR-10b, and miR-942-5p ( Singh et al, 2018 ; Fang et al, 2020 ; Wang et al, 2020b ). Among them, the most in-depth research is of miR-942-5p, reported by Wang et al (2020b) In that study, miR-942-5p showed significantly low expression in oral squamous carcinoma in the background of OSMF and could directly target latent transforming growth factor beta binding protein 2 (LTBP2), which further blocked the PI3K/Akt/mTOR signaling pathway ( Wang et al, 2020b ).…”

Section: Role Of Mirnas In the Canonical And Noncanonical Tgf-β Signaling Pathways In Fibrotic Diseases Affecting Different Organsmentioning

confidence: 99%

“…In recent years, many studies have investigated miRNAs related to OSMF, including miR-21, miR-10b, and miR-942-5p ( Singh et al, 2018 ; Fang et al, 2020 ; Wang et al, 2020b ). Among them, the most in-depth research is of miR-942-5p, reported by Wang et al (2020b) In that study, miR-942-5p showed significantly low expression in oral squamous carcinoma in the background of OSMF and could directly target latent transforming growth factor beta binding protein 2 (LTBP2), which further blocked the PI3K/Akt/mTOR signaling pathway ( Wang et al, 2020b ). The regulatory mechanisms of miRNAs in the canonical and non-canonical TGF-β signaling pathway are summarized as shown in Figure 1 .…”

Section: Role Of Mirnas In the Canonical And Noncanonical Tgf-β Signaling Pathways In Fibrotic Diseases Affecting Different Organsmentioning

confidence: 99%

MicroRNAs in Transforming Growth Factor-Beta Signaling Pathway Associated With Fibrosis Involving Different Systems of the Human Body

Hong

Wang

et al. 2021

Front. Mol. Biosci.

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Fibrosis, a major cause of morbidity and mortality, is a histopathological manifestation of many chronic inflammatory diseases affecting different systems of the human body. Two types of transforming growth factor beta (TGF-β) signaling pathways regulate fibrosis: the canonical TGF-β signaling pathway, represented by SMAD-2 and SMAD-3, and the noncanonical pathway, which functions without SMAD-2/3 participation and currently includes TGF-β/mitogen-activated protein kinases, TGF-β/SMAD-1/5, TGF-β/phosphatidylinositol-3-kinase/Akt, TGF-β/Janus kinase/signal transducer and activator of transcription protein-3, and TGF-β/rho-associated coiled-coil containing kinase signaling pathways. MicroRNA (miRNA), a type of non-coding single-stranded small RNA, comprises approximately 22 nucleotides encoded by endogenous genes, which can regulate physiological and pathological processes in fibrotic diseases, particularly affecting organs such as the liver, the kidney, the lungs, and the heart. The aim of this review is to introduce the characteristics of the canonical and non-canonical TGF-β signaling pathways and to classify miRNAs with regulatory effects on these two pathways based on the influenced organ. Further, we aim to summarize the limitations of the current research of the mechanisms of fibrosis, provide insights into possible future research directions, and propose therapeutic options for fibrosis.

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“…Thus, APOC2 correlated markedly with shorter survival of patients with a more aggressive tumor phenotype, indicating that APOC2 could be used as a prognostic indicator for patients with GC ( Table 1). The proteomics data showed that extracellular matrix components related to the DEPs are highly expressed in GC PM tissue, and previous studies showed that EMT is critical for the development of cancer via the transformation of epithelial cells into mesenchymal cells to promote tumor cell metastasis (51). Interestingly, when APOC2 was knocked down in GC cells, the malignant phenotypes of the GC cells and the expression of EMT markers were inhibited.…”

Section: Discussionmentioning

confidence: 76%

Apolipoprotein C-II induces EMT to Promote Gastric Cancer Peritoneal Metastasis via PI3K/AKT/mTOR Pathway

Wang

Yang

et al. 2021

Preprint

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Background: Peritoneal metastasis (PM) occurs frequently in patients with gastric cancer (GC) and confers poor survival. Lipid metabolism and epithelial-mesenchymal transition (EMT) play an important role in GC metastasis. As Apolipoprotein C-II (APOC2) is a key protein in lipid metabolism, few studies have investigated the role of APOC2 in PM. This study aims to elucidate the potential molecular mechanism of APOC2 in the PM of GC.Methods: The Tandem Mass Tagging (TMT) method followed by liquid chromatography-tandem mass spectrometry-based proteomics analysis was used to compare the levels of differentially expressed proteins between human PM and GC tissues. APOC2 expression was evaluated by immunoblotting, and immunohistochemistry analysis (n = 111). APOC2 over-expression and knock-down expression cell models were developed and tested in vitro. RNA sequencing analysis evaluated the changes in gene expression after APOC2 knockdown in GC cells. The Agilent Seahorse XF platform and lipid staining assay were used to evaluate the role of APOC2 in lipid metabolism of GC cells. Spheroid cell invasion assay, apoptosis assay, colony formation assay, wound-healing assays, and transwell assays were performed and peritoneal implants into nude mice were done to assess the biological effects of APOC2. The underlying mechanisms were investigated using Western blot, inhibitor or activator treatment assays.Results: APOC2 was highly abundant in GC cells and PM tissues. And high APOC2 levels in GC tissues correlated with poor patient prognosis. Knockdown of APOC2 inhibited the malignant phenotype of cancer cells and EMT significantly. Massive gene expression alterations after APOC2 knockdown, which were associated with various signaling pathways, especially the PI3K/AKT signaling pathway and lipid metabolism. Furthermore, the regulatory effects of APOC2 on the EMT were partially attributed to the PI3K/AKT/mTOR signaling pathway. The results in vivo also showed that APOC2 modulated GC PM.Conclusions: We verified that knockdown of APOC2 suppressed GC cell Lipid metabolism, proliferation, migration, invasion, and EMT, accompanied by inactivation of PI3K/AKT/mTOR signaling pathway. APOC2 overexpression had the opposite effects GC cell phenotypes and mechanisms. Collectively, our results identified APOC2 in PM as a potential therapeutic target.

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The circEPSTI1/mir-942-5p/LTBP2 axis regulates the progression of OSCC in the background of OSF via EMT and the PI3K/Akt/mTOR pathway

Cited by 103 publications

References 34 publications

circFBXW7 attenuates malignant progression in lung adenocarcinoma by sponging miR-942-5p

circFBXW7 attenuates malignant progression in lung adenocarcinoma by sponging miR-942-5p

MicroRNAs in Transforming Growth Factor-Beta Signaling Pathway Associated With Fibrosis Involving Different Systems of the Human Body

Apolipoprotein C-II induces EMT to Promote Gastric Cancer Peritoneal Metastasis via PI3K/AKT/mTOR Pathway

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