miR‐296 inhibits proliferation and induces apoptosis by targeting <scp>FGFR</scp>1 in human hepatocellular carcinoma

Wang, Liyan; Bo, Xiaotong; Zheng, Qianqian; Xiao, Xuejun; Wu, Linling; Li, Bin

doi:10.1002/1873-3468.12442

Cited by 37 publications

(35 citation statements)

References 28 publications

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“…The function of FGFR1 in HCC was substantially uncovered in previous studies. For example, FGFR1 restoration promoted HCC cell proliferation and cell cycle progression but limited apoptosis [30]. Keratin 19 silence could weaken the expression of FGFR1, leading to the inhibition of HCC cell growth and the promotion of cell apoptosis [31].…”

Section: Discussionmentioning

confidence: 99%

Circ_0015756 aggravates hepatocellular carcinoma development by regulating FGFR1 via sponging miR-610

Guo¹,

Zhao²,

Wei³

et al. 2020

Preprint

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Background: Hepatocellular carcinoma (HCC) is the leading threat of cancer-related death in humans with poor therapeutic effects. Circular RNAs (circRNAs) are important indicators in cancer diagnosis and prognosis. This study intended to explore the function and mechanism of circ_0015756 in HCC, providing the additional opinion for HCC treatment.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of circ_0015756 and miR-610. Cell viability was assessed by cell counting kit-8 (CCK-8) assay, and colony formation capacity was ascertained by colony formation assay. Cell proliferation and invasion were monitored by transwell assay. Cell cycle progression and apoptosis were analyzed by flow cytometry assay. Circ_0015756 oncogenicity was determined by Xenograft models. The prediction of targets was performed using the bioinformatics tools, and the verification of targeted relationship was conducted using RNA pull-down, RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. The expression level of fibroblast growth factor receptor 1 (FGFR1) was measured by western blot.Result: The expression of circ_0015756 was increased in HCC tissues, serums and cells. Circ_0015756 downregulation impaired HCC cell viability, colony formation capacity, invasion and migration, induced cell cycle arrest and apoptosis, and inhibited tumor growth in vivo. MiR-610 was ensured as a target of circ_0015756, and miR-610 absence reversed the effects of circ_0015756 downregulation. Further, FGFR1 was interacted by miR-610, and FGFR1 overexpression overturned the effects of miR-610 restoration in vitro. Circ_0015756 could regulate FGFR1 expression by targeting miR-610.Conclusion: Circ_0015756 played its tumorigenic properties in HCC by activating FGFR1 and sponging miR-610, and circ_0015756 was expected to be a vital indicator in HCC diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Circ_0015756 aggravates hepatocellular carcinoma development by regulating FGFR1 via sponging miR-610

Guo¹,

Zhao²,

Wei³

et al. 2020

Preprint

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“…As an important subgroup of short noncoding RNAs, micro-RNAs (miRs) play essential roles in a large array of physiologic and pathologic conditions in which their aberrant expression has been correlated with disease pathogenesis and progression, including fibrogenesis (14,15). As previously reported by Wang et al (16), the low expression of miR-296 has been earmarked as a responsible element associated with unfavorable survival rates and poor prognoses among patients with hepatocellular carcinoma, whereas up-regulated expression levels of miR-296 exhibit tumor suppressor capabilities. Additionally, evidence has been presented indicating that DOK1 and DOK2 contribute to progressive fibrosis (17).…”

mentioning

confidence: 93%

“…As previously reported by Wang et al . (16), the low expression of miR‐296 has been earmarked as a responsible element associated with unfavorable survival rates and poor prognoses among patients with hepatocellular carcinoma, whereas up‐regulated expression levels of miR‐296 exhibit tumor suppressor capabilities. Additionally, evidence has been presented indicating that DOK1 and DOK2 contribute to progressive fibrosis (17).…”

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confidence: 99%

Long noncoding RNA AK089579 inhibits epithelial‐to‐mesenchymal transition of peritoneal mesothelial cells by competitively binding to microRNA‐296‐3p via DOK2 in peritoneal fibrosis

2019

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Peritoneal fibrosis (PF) represents a well‐recognized complication associated with continuous ambulatory peritoneal dialysis therapy, characterized by a reversible epithelial‐to‐mesenchymal transition (EMT) at the early stage. The aim of the current study was to investigate the effects linked with the long noncoding RNA (IncRNA) AK089579 on the EMT of peritoneal mesothelial cells (PMCs) as well as the associated regulatory mechanisms of AK089579 downstream of tyrosine kinase 2 (DOK2) and microRNA‐296‐3p (miR‐296‐3p). Enrichment analysis, gene intersection association analysis, and a gene‐gene intersection network were initially constructed to ascertain whether AK089579 regulated the expression of DOK2 through the mediation of miR‐296‐3p via the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in PF. After the PF mouse model had been constructed, the expression of the proteins associated with the JAK2/STAT3 signaling pathway and EMT and PMC migration and invasion were all determined accordingly. Based on the obtained results, AK089579 was determined to function as a competing endogenous RNA for miR‐296‐3p while acting to up‐regulate the expression of DOK2, which is a target gene of miR‐296‐3p. AK089579 was detected to confer an inhibitory effect on the activation of the JAK2/STAT3 signaling pathway, whereby the migration and invasion of PMCs among the mice models were suppressed. Meanwhile, up‐regulated miR‐296‐3p and down‐regulated DOK2 produced contrasting effects when compared with the aforementioned findings. Treatment with wpl0066, a JAK2/STAS3 signaling pathway inhibitor, was shown to reverse the effects exerted by up‐regulated miR‐296‐3p. Taken together, the central findings of the current study present evidence highlighting the capability of the IncRNA AK089579 to bind competitively to miR‐296‐3p and indirectly enhance the expression of DOK2, which in turn suppresses the activation of the JAK2/STAT3 signaling pathway, whereby the EMT, migration, and invasion of PMCs was inhibited in PF.—Zhang, X. W., Wang, L., Ding, H. Long noncoding RNA AK089579 inhibits epithelial‐to‐mesenchymal transition of peritoneal mesothelial cells by competitively binding to microRNA‐296‐3p via DOK2 in peritoneal fibrosis. FASEB J. 33, 5112–5125 (2019). http://www.fasebj.org

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“…Recent studies have reported that miR‐296‐5p could participate in the initiation and progression of several types of human diseases, particularly cancers. For instance miR‐296 exerted a tumour suppressive role in hepatocellular carcinoma (HCC) by targeting fibroblast growth factor receptor 1 and suppressing the proliferation of HCC cells . In addition, the expression of miR‐296‐5p in liver samples of patients with nonalcoholic steatohepatitis was lower than that in patients with simple steatosis or the control group.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA KCNQ1OT1 promotes apoptosis in neuroblastoma cells by regulating miR‐296‐5p/Bax axis

Liu

Zhao

et al. 2019

The FEBS Journal

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Long noncoding RNAs (lncRNAs) are emerging as important regulators of multiple cellular processes such as cell invasion, growth, apoptosis and differentiation. LncRNAs can function as competing endogenous RNAs (ceRNAs) which sponge and sequester microRNA (miRNA) to regulate specific targets. Previously, we found that the target genes of several miRNAs, including FADD, Fas, Casp and Bax, are related to neuronal apoptosis and form a regulatory network. Among several factors, microRNA‐296‐5p expression was found to be negatively correlated with caspase activity and apoptosis. Here, we aimed to investigate the role of miR‐296‐5p in neuroblastoma (NB) cells. By performing quantitative real‐time PCR (qRT‐PCR), western blot and flow cytometry assays we analysed the expression of apoptotic markers in NB cells transfected with miR‐296‐5p mimics or inhibitor. Pathway‐specific PCR array allowed us to identify the target genes of miR‐296‐5p. Using LncBase online tool, we predicted lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) as an upstream regulator of miR‐296‐5p. The binding of KCNQ1OT1 and miR‐296‐5p was validated via RNA immunoprecipitation and Biotin pull‐down assays. We also demonstrate that miR‐296‐5p suppresses apoptosis of NB cells in vitro and in vivo. Mechanistically, miR‐296‐5p directly bound the 3′UTR of Bax mRNA, thus repressing Bax at the mRNA and protein level. Moreover, through bioinformatic analysis and molecular experiments, we showed that KCNQ1OT1 sponged miR‐296‐5p and impaired its effect on NB cell apoptosis. In summary, KCNQ1OT1 is a potent promoting factor of cell apoptosis, which acts by sponging miR‐296‐5p and upregulating Bax. Our findings identify a regulatory axis of cell fate in NB cells.

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miR‐296 inhibits proliferation and induces apoptosis by targeting FGFR1 in human hepatocellular carcinoma

Cited by 37 publications

References 28 publications

Circ_0015756 aggravates hepatocellular carcinoma development by regulating FGFR1 via sponging miR-610

Circ_0015756 aggravates hepatocellular carcinoma development by regulating FGFR1 via sponging miR-610

Long noncoding RNA AK089579 inhibits epithelial‐to‐mesenchymal transition of peritoneal mesothelial cells by competitively binding to microRNA‐296‐3p via DOK2 in peritoneal fibrosis

Long noncoding RNA KCNQ1OT1 promotes apoptosis in neuroblastoma cells by regulating miR‐296‐5p/Bax axis

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