<p>Circ_0015756 Aggravates Hepatocellular Carcinoma Development by Regulating FGFR1 via Sponging miR-610</p>

Abstract

Background: Hepatocellular carcinoma (HCC) is the leading threat of cancer-related death in humans. Increasing studies show that 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. Materials and 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 migration 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 targets of circ_0015756 and miR-610 were predicted by bioinformatics tools and validated 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. Results: 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 targeted by miR-610, and FGFR1 overexpression overturned the effects of miR-610 restoration in HCC cells. Circ_0015756 could regulate FGFR1 expression by targeting miR-610. Conclusion: Circ_0015756 played its tumorigenic properties in HCC by activating FGFR1 via sponging miR-610, and circ_0015756 was expected to be a vital indicator in HCC diagnosis and treatment.

Circ_0072995 Promotes Proliferation and Invasion via Regulating miR-1253/EIF4A3 Signaling in HCC

“…15 For example, circ_0015756 is upregulated in HCC and promotes cell proliferation, migration and invasion. 16 CircRNA cIARS affects HCC ferroptosis by binding to ALKBH5. 17 Circ_0046599 initiates HCC development and promotes metastasis via miR-1258/RPN2 signaling.…”

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

“…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 ].…”

“…(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 ]. …”

“…In contrast, multiple upregulated cicrRNA-based axes including circEIF3I/miR-526b-5p/HGF/c-Met and circ_0015756/miR-610/FGFR1 have been implicated in cell signaling in HCC tissues and cell lines such as SNU-387 and Huh7 [ 131 , 132 ]. The significant overexpression of hsa_circ_0085616 has been shown to promote proliferation of HCC cells as compared to normal liver cells by influencing β-catenin, phosphorylated extracellular signal-regulated kinase ( p -ERK), and phosphorylated protein kinase B ( p -PKB/Akt) levels [ 133 ].…”

Recent Update on the Role of Circular RNAs in Hepatocellular Carcinoma

“…Increased cellular proliferation and invasion by a mechanism involving FGFR1. 44 circ-0001955 miR-516a-5p Binding of miR-516a-5p resulting in de-repression of TRAF6 and MAPK11. 85 mi-R-145-5p Binding of miR-145-5p augmented activity of the NRAS proto-oncogene.…”