SiRNA of Frizzled-9 suppresses proliferation and motility of hepatoma cells

Abstract

Abstract. Frizzled (Fz), a receptor of Wnt ligands, plays key roles in liver carcinogenesis. Its expression was analyzed as part of a search for a target of molecular therapy for hepatocellular carcinoma (HCC) and hepatoblastoma (HB). Fz genes were analyzed by RT-PCR in HCC cell lines HLE, HLF, PLC/PRF/5, Huh-7 and Hep3B, HB cell lines Huh-6 and HepG2, HeLa cells, human normal fetal and adult liver. We transfected PLC/PRF/5, HLE, Huh-6, and HeLa cells with Fz9-small interfering RNA (Fz9-siRNA). Five days after transfection, cell proliferation was analyzed by MTS assay and cell motility by wound assay with H&E staining. Subsequently, the expressions of cyclin D1 and caspase-3 were analyzed by Western blot analysis. Fz9-siRNA decreased the expression of Fz9 gene in all cell lines. MTS assay showed that Fz9-siRNA significantly suppressed cell proliferation and cell motility in all cell lines. The expression of cyclin D1 was also suppressed by Western blotting. Cleaved caspase-3 did not appear and apoptosis was not observed in any of the cell lines tested. We demonstrated that Fz9 plays an essential role in carcinogenesis of HB and HCC, concluding that Fz9-siRNA could represent a useful therapeutic target for HB and HCC.

Comparative Analysis of Multiple Neurodegenerative Diseases Based on Advanced Epigenetic Aging Brain

“…It has been reported that the identified biomarkers are closely related to aging and ND ( Table 2 ; Salmerón et al, 2001 ; Hu et al, 2004 ; Katoh, 2008 ; Qiu and Ghosh, 2008 ; Fujimoto et al, 2009 ; Su et al, 2009 ; Kozarova et al, 2011 ; Euskirchen et al, 2012 ; Berwick and Harvey, 2014 ; Lopez-Pelaez et al, 2014 ; Alquézar et al, 2016 ; Chailangkarn et al, 2016 ; Densham et al, 2016 ; Husain et al, 2016 ; Pîrşcoveanu et al, 2017 ; Kurihara et al, 2019 ; Monteiro and Forti, 2019 ). Interestingly, these related functions (i.e., DNA damage repair response, mitochondrial dysfunction, or Ca ion homeostasis disorder), further indicated the imbalance of cellular homeostasis, and abnormal cell death was further induced across various ND types.…”

An <i>In Silico</i> Analysis Identified FZD9 as a Potential Prognostic Biomarker in Triple-Negative Breast Cancer Patients

“…The FZD9 expression was increased in colorectal cancer tissues than in normal tissues and expressed in hepatocellular carcinoma (HCC) cell line, but absent in normal fetal and adult liver tissues (31,32). Elsewhere, FZD9 knockdown reduced the cyclin D1 levels, migration, and cell proliferation in HCC cells (32).…”

“…The FZD9 expression was increased in colorectal cancer tissues than in normal tissues and expressed in hepatocellular carcinoma (HCC) cell line, but absent in normal fetal and adult liver tissues (31,32). Elsewhere, FZD9 knockdown reduced the cyclin D1 levels, migration, and cell proliferation in HCC cells (32). In contrast, non-small cell lung cancer cells with ectopic expression of Wnt7a/Fzd9 showed an increase in the PPARy activity and inhibited the transformation of growth suggesting an anti-tumorigenic effect (33).…”

Analysis of Gene Expression of miRNA-106b-5p and TRAIL in the Apoptosis Pathway in Gastric Cancer

“…In a more refined analysis, the miRWalk databases were used to determine validated targets miR-106b-5p genes involved in gastric carcinogenesis and 14 genes from this pathway were found: APC (regulator of the WNT signaling pathway), CCND1 (cyclin D1) CDKN1A (cyclin-dependent kinase inhibitor 1), E2F1, E2F2, E2F3 (transcription factor 1, 2, and 3, respectively), FZD9 (frizzled class receptor 9), MAPK1 (mitogen-activated protein kinase 1), MYC (proto-oncogene BHLH transcription factor), RB1 (transcriptional corepressor 1), SMAD4 (SMAD family member 4), TCF7L2 (transcription factor 7-like 2), TGFBR2 (transforming growth factor β receptor 2), and TP53 (tumor protein p53). Considering the main functions described in the process of carcinogenesis, these genes are involved in cell cycle regulation and tumor progression, cell growth, adhesion and migration, proliferation, differentiation, genome stability, DNA repair, and apoptosis [42][43][44][45][46][47][48][49].…”