Silencing CircEIF3I/miR-526b-5p Axis Epigenetically Targets HGF/c-Met Signal to Hinder the Malignant Growth, Metastasis and Angiogenesis of Hepatocellular Carcinoma

Liu, Yang; Xiao, Xia; Wang, Jingying; Wang, Yitong; Yu, Yanhui

doi:10.1007/s10528-022-10239-y

Cited by 8 publications

(6 citation statements)

References 59 publications

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“…According to the study from Kong Q et al, miR-526b-5p was proved to be sponged by circUGGT2 and regulate its target gene RAB1A, thereby inhibiting HCC development 12 . Another study from Liu Y et al, confirmed that miR-526b-5p interacting with circEIF3I and target gene HGF attenuates the HCC tumor growth 13 . The previous studies indicated that there were multiple circRNAs and mRNAs in HCC to interact with miR-526b-5p.…”

Section: Discussionmentioning

confidence: 86%

“…In cervical cancer, circ_0002762 could accelerate the tumorigenesis by sponging miR-526b-5p to upregulate HK2 11 . In HCC, miR-526b-5p was reported to interact circUGGT2 or circEIF3I, thereby playing the inhibitory role in HCC development 12 , 13 . The studies on miR-526b-5p in HCC suggest that miR-526b-5p can interact with different circRNAs.…”

Section: Introductionmentioning

confidence: 99%

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Hsa_circ_0119412 is a tumor promoter in hepatocellular carcinoma by inhibiting miR-526b-5p to upregulate STMN1

Wu,

Tang,

Zhou

et al. 2023

Cancer Biology & Therapy

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Hepatocellular carcinoma (HCC) is always deemed a deadly malignancy worldwide. Non-coding RNAs, including circRNAs, are becoming more widely recognized as essential regulators of the malignant development of HCC. Thus, we elaborated the regulating role of hsa_circ_0119412 in HCC advancement. The qRT-PCR was done to estimate the expressions of hsa_circ_0119412, miR-526b-5p, and Stathmin 1 (STMN1) in HCC (clinical samples and cell lines), and immunoblotting was used to detect STMN1 protein level in HCC cell lines. The stability of the circRNA was checked by processing with ribonuclease R. The proliferative potential of HCC cells was examined via the CCK-8 assay and the migratory potential by the wound healing assay. Immunoblotting was done to examine Bax and Bcl-2 (apoptosis-related proteins). Luciferase and RIP assays were employed to establish the direct interactions among miR-526b-5p and hsa_circ 0119412/STMN1. In vivo tumor growth was measured by doing a xenograft tumor experiment. In the tissues of HCC patients and cell lines derived from HCC cells, hsa_circ_0119412 was distinctly over-expressed. Knocking down hsa_circ_0119412 impeded proliferation and migration while inducing apoptosis in HCC cells. Moreover, silencing hsa_circ_0119412 diminished tumor weight and volume in vivo. Interestingly, miR-526b-5p inhibition partially restored the anti-tumor effects of silencing hsa_circ_0119412. STMN1 expression was also abundant in HCC, suggesting that it play a tumor-promoting role. Mechanistically, hsa_circ_0119412 sponged miR-526b-5p, resulting in STMN1 upregulation and thus facilitating the progression of HCC. In conclusion, this study reveals that hsa_circ_0119412 knockdown attenuates the progression of HCC by targeting miR-526b-5p/STMN1 axis.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Hsa_circ_0119412 is a tumor promoter in hepatocellular carcinoma by inhibiting miR-526b-5p to upregulate STMN1

Wu,

Tang,

Zhou

et al. 2023

Cancer Biology & Therapy

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“…An increasing number of experiments have demonstrated that circRNAs can promote the development of HCC by regulating various signals involved with the cell cycle, proliferation, differentiation, cell survival and apoptosis, leading to abnormal activation of several molecules in signal transduction pathways [18] . Studies have con rmed that circRNAs can act via the AKT/ERK [19] , Wnt/βcatenin [20] , nuclear factor-kappa B [21], hedgehog [22] , c-Met [23] , JAK2/STAT3 [24] and other signalling pathways and are involved in the malignant biological behaviours of HCC. Recent studies have con rmed that circRNAs not only exert biological functions through the above signalling pathways but also affect the biological processes of HCC through other pathways.…”

Section: Discussionmentioning

confidence: 99%

RNA-sep analysis of circular RNAs and ceRNA networks in human hepatocellular carcinoma

Liu

Dong

Chen

et al. 2022

Preprint

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Objective An increasing number of circular RNAs (circRNAs) have been identified as emerging competing endogenous RNAs (ceRNAs) that play important roles in hepatocellular carcinoma (HCC), but numerous circRNAs remain unexplored. The aim of this study was to explore the mechanism of action of differentially expressed circRNAs and their ceRNA networks in HCC. Methods Second-generation sequencing technology was used to analyse the expression of circRNAs in cancerous and paired paraneoplastic tissues from five patients with HCC. The circRNAs with a P value of less than 0.01, with an original signal value greater than 100 and ranked among the top ten upregulated circRNAs were selected and validated by quantitative reverse transcription polymerase chain reaction (qRT‒PCR) in paired cancer and paraneoplastic tissues from another 34 HCC patients. The downstream miRNAs and mRNAs of the circRNAs were explored through database analysis, and finally, the ceRNA networks and circRNA–miRNA–mRNA axes based on these ten circRNAs were constructed. Results By sequencing, we identified 9658 differentially expressed circRNAs on all chromosomes, of which 3862 were significantly upregulated and 5796 were significantly downregulated. RT-qPCR was performed to validate the top ten upregulated circRNAs, and the results were generally consistent with the sequencing results. After qRT‒PCR validation, five circRNAs (hsa_circ_0079875, hsa_circ0091580, hsa_circ0091581, hsa_circ0004788 and hsa_circ_0059730) were selected for further analysis. First, the downstream miRNAs and mRNAs of these five circRNAs were predicted to construct circRNA-miRNA‒mRNA network diagrams. The 1482 upregulated mRNAs identified in the GEPIA database overlapped with the 278 mRNAs in the ceRNA networks, and 14 overlapping genes were identified. Further bioinformatics analysis revealed four mRNAs (ADSL, AP3B1, MAPRE1, and TRNP1) and five circRNA–miRNA–mRNA axes that were negatively correlated with HCC prognosis. Conclusions Numerous differentially expressed circRNAs exist in HCC, and most can regulate the biological behaviour of HCC through circRNA-miRNA‒mRNA networks. Bioinformatics analysis showed that the ceRNA regulatory axes in HCC have high diagnostic and prognostic value and deserve further exploration. This study aims to provide new research ideas related to HCC pathogenesis and treatment options.

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“…In several human liver cancer lines, lncRNA-based KTN1-AS1/miR-23c/ERBB2IP axis activates MAPK/ERK1/2 pathway [ 85 ], whereas HULC/miR-15a/PTEN [ 95 ], UBE2R2/miR-302b/EGFR and ZEB1-AS1/miR-302b/EGFR axes activate PI3K/PKB(Akt) pathway [ 96 , 97 ], and LINC00662/miR-15a/β-catenin axis activates Wnt/β-catenin signaling [ 102 ], SBF2-AS1/miR-140-5p/TGFBR1 activates TGFβ-signaling [ 103 ]. In HCC tissues and cell lines such as SNU-387 and Huh7, circRNA-based circEIF3I/miR-526b-5p/HGF/c-Met and circ_0015756/miR-610/FGFR1 as well as circ_0015756/miR-7/FAK axes are identified [ 131 , 132 , 138 ]. Also, hsa_circ_0016788/hsa_circ_0016788/CDK4/6 axis regulates cell cycle [ 135 ].…”

Section: Del-dem-deg Network In Hccmentioning

confidence: 99%

“…(A) lncRNAs implicated in cell signaling [ 63 , 64 , 70 , 74 , 85 , [95] , [96] , [97] , [98] , [99] , [100] , [101] , [102] , [103] , [104] ], metabolic reprogramming [ 108 , 111 ], epithelial-mesenchymal transition/morphogenesis [ 81 , 82 , 86 , 89 ], tumor microenvironment remodeling [ 88 ], cell cycle [ 107 ], and apoptosis [ 84 , 87 , 103 , 106 ]. (B) CircRNAs implicated in cell signaling [ 132 , 133 ], cell cycle [ 108 , 118 , 134 , 135 ], transcriptional regulation [ 136 , 137 , 154 ], metabolic reprogramming [ [145] , [146] , [147] ], epithelial-mesenchymal transition [ [139] , [140] , [141] , [142] ], immune response [ 144 , 149 , 150 ], and angiogenesis [ 129 , 131 ]. …”

Section: Del-dem-deg Network In Hccmentioning

confidence: 99%

Differentially expressed non-coding RNAs and their regulatory networks in liver cancer

Moldogazieva,

Zavadskiy,

Astakhov

et al. 2023

Heliyon

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Silencing CircEIF3I/miR-526b-5p Axis Epigenetically Targets HGF/c-Met Signal to Hinder the Malignant Growth, Metastasis and Angiogenesis of Hepatocellular Carcinoma

Cited by 8 publications

References 59 publications

Hsa_circ_0119412 is a tumor promoter in hepatocellular carcinoma by inhibiting miR-526b-5p to upregulate STMN1

Hsa_circ_0119412 is a tumor promoter in hepatocellular carcinoma by inhibiting miR-526b-5p to upregulate STMN1

RNA-sep analysis of circular RNAs and ceRNA networks in human hepatocellular carcinoma

Differentially expressed non-coding RNAs and their regulatory networks in liver cancer

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