hsa_circ_0001955 Enhances In Vitro Proliferation, Migration, and Invasion of HCC Cells through miR-145-5p/NRAS Axis

Ding, Bo; Fan, Weimin; Lou, Weiyang

doi:10.1016/j.omtn.2020.09.007

Cited by 62 publications

(59 citation statements)

References 26 publications

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“…We found that there were 5 overlapping circRNAs (hsa_circ_0067934, hsa_circ_0003528, hsa_circ_0001955, hsa_circ_0008274, and hsa_circ_0072088) in the top 50 upregulated circRNAs in the GSE78520 and GSE94508 microarray datasets (Figure 1A). Among the 5 overlapping circRNAs, the biological role of hsa_circ_0067934 [27], hsa_circ_0001955 [28], hsa_circ_0008274 [29], and hsa_circ_0072088 [30] in HCC had been verified. Thus, we choose hsa_circ_0003528 for further exploration.…”

Section: Resultsmentioning

confidence: 99%

CircSEC24A promotes tumor progression through sequestering miR-455-3p in hepatocellular carcinoma

Liao¹,

Yang²,

Luo³

et al. 2021

neo

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Hepatocellular carcinoma (HCC) ranks third in the cause of death due to cancer. Circular RNA circSEC24 Homolog A (circSEC24A) has been uncovered to be upregulated in liver cancer.However, the function of circSEC24A in HCC is indistinct.We analyzed the microarray datasets GSE78520 and GSE94508 to search for differentially expressed circRNAs associated with HCC. Expression of circSEC24A, microRNA (miR)-455-3p, and protein phosphatase, Mg2+/Mn2+ dependent 1F (PPM1F) mRNA was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Loss-of-function experiments were conducted to validate the biological function of circSEC24A in HCC cells in vitro and in vivo. Protein levels were evaluated by western blotting and immunohistochemistry (IHC). The relationship between circSEC24A or PPM1F and miR-455-3p was verified by a dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. circSEC24A was overexpressed in HCC. circSEC24A silencing decreased xenograft tumor growth in vivo and repressed proliferation, metastasis, invasion, epithelial-to-mesenchymal transition (EMT), induced cell cycle arrest, and apoptosis of HCC cells in vitro. circSEC24A acted as a molecular sponge to sequester miR-455-3p, resulting in elevating the expression of PPM1F. miR-455-3p inhibitor reversed the suppressive impact of circSEC24A silencing on malignant behaviors of HCC cells. PPM1F overexpression offsets the inhibitory effect of miR-455-3p mimic on malignant behaviors of HCC cells. circSEC24A sponged miR-455-3p to elevate the PPM1F expression, resulting in accelerating malignant behaviors of HCC cells. The study provided a potential therapeutic target for patients with HCC.

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Section: Resultsmentioning

confidence: 99%

CircSEC24A promotes tumor progression through sequestering miR-455-3p in hepatocellular carcinoma

Liao¹,

Yang²,

Luo³

et al. 2021

neo

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“…By knocking down the expression of ESRP2 in the HCC model cell line Huh-7, we observed a significant upregulation of three circRNAs (hsa_circ_0001955, hsa_circ_0008016, and hsa_circ_0008274). These circRNAs are upregulated in HCC, and the oncogenic role in HCC was already confirmed for two [ 48 , 49 ]. Since these circRNAs are upregulated after ESRP2 knockdown in cell lines, this indicates that ESRP2 could inhibit the biogenesis of these circRNAs in the liver.…”

Section: Discussionmentioning

confidence: 95%

Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

Razpotnik

Nassib

Kunej

et al. 2021

IJMS

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Circular RNAs (circRNAs) are increasingly recognized as having a role in cancer development. Their expression is modified in numerous cancers, including hepatocellular carcinoma (HCC); however, little is known about the mechanisms of their regulation. The aim of this study was to identify regulators of circRNAome expression in HCC. Using publicly available datasets, we identified RNA binding proteins (RBPs) with enriched motifs around the splice sites of differentially expressed circRNAs in HCC. We confirmed the binding of some of the candidate RBPs using ChIP-seq and eCLIP datasets in the ENCODE database. Several of the identified RBPs were found to be differentially expressed in HCC and/or correlated with the overall survival of HCC patients. According to our bioinformatics analyses and published evidence, we propose that NONO, PCPB2, PCPB1, ESRP2, and HNRNPK are candidate regulators of circRNA expression in HCC. We confirmed that the knocking down the epithelial splicing regulatory protein 2 (ESRP2), known to be involved in the maintenance of the adult liver phenotype, significantly changed the expression of candidate circRNAs in a model HCC cell line. By understanding the systemic changes in transcriptome splicing, we can identify new proteins involved in the molecular pathways leading to HCC development and progression.

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“…CircRNAs are involved in the development of various cancers 12–14 . In HCC, a previous study demonstrates that circ_0001955 expression is upregulated, and knockdown of circ_0001955 markedly inhibits the proliferation, migration, and invasion of HCC cells 15 . Another study reports that circRNA_103809, whose expression is dysregulated in HCC, can promote HCC development by regulating miR‐377‐3p/EGFR1/ERK axis 16 .…”

Section: Discussionmentioning

confidence: 99%

Circ_0072088 promotes progression of hepatocellular carcinoma by activating JAK2/STAT3 signaling pathway via miR‐375

Xiao

2021

IUBMB Life

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Circular RNAs feature prominently in cancer development. Nonetheless, the role of circ_0072088 in hepatocellular carcinoma (HCC) remains unclear. GEO databases (GSE97332, GSE108724, GSE36915, and GSE33006) were used to screen out the differentially expressed circRNAs, miRNAs, and mRNA in HCC. The expressions of circ_0072088, miR‐375, and Janus Kinase 2 (JAK2) mRNA in HCC tissue and cell lines were determined with quantitative real‐time polymerase chain reaction. RNase R treatment assay was used to measure the stability of circ_0072088, and subcellular fraction assay was used to detect the localization of circ_0072088. Cell counting kit‐8 assay, flow cytometry, and Transwell assay were used to measure proliferation, apoptosis, migration, and invasion of HCC cells. RNA immunoprecipitation and dual‐luciferase reporter gene assay were employed for investigating the binding sequence between circ_0072088 and miR‐375, as well as miR‐375 and JAK2 3′UTR. Western blot assay was used to detect the expression of JAK2 and p‐STAT3 after circ_0072088 and miR‐375 were selectively regulated. Circ_0072088 and JAK2 mRNA expressions were highly expressed in HCC tissues and cell lines while miR‐375 expression was remarkably downregulated. Circ_0072088 was resistant to RNase R treatment and mainly located in the cytoplasm of HCC cells. The transfection of circ_0072088 overexpression plasmid or miR‐375 inhibitors promoted the proliferation, migration, and invasion, and inhibited the apoptosis of HCC cells, whereas transfection of circ_0072088 siRNA or miR‐375 mimics exerted opposite effects. Besides, miR‐375 was confirmed as a target of circ_0072088 and miR‐375 could further downregulate the expression of JAK2. MiR‐375 mimics could reverse the upregulation of JAK2 and p‐STAT3 protein induced by circ_0072088 overexpression. Circ_0072088 can enhance the proliferation, migration, and invasion, and impede apoptosis of HCC cells. Mechanistically, circ_0072088 activates JAK2/STAT3 signaling pathway by serving as a molecular sponge of miR‐375.

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hsa_circ_0001955 Enhances In Vitro Proliferation, Migration, and Invasion of HCC Cells through miR-145-5p/NRAS Axis

Cited by 62 publications

References 26 publications

CircSEC24A promotes tumor progression through sequestering miR-455-3p in hepatocellular carcinoma

CircSEC24A promotes tumor progression through sequestering miR-455-3p in hepatocellular carcinoma

Identification of Novel RNA Binding Proteins Influencing Circular RNA Expression in Hepatocellular Carcinoma

Circ_0072088 promotes progression of hepatocellular carcinoma by activating JAK2/STAT3 signaling pathway via miR‐375

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