Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Abstract

Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) has been reported in cancers but its role and potential molecular mechanism in hepatocellular carcinoma (HCC) is unclear. Therefore, we aimed to investigate the clinical value and molecular mechanism of CELSR3 in HCC using an in vitro experiment, a meta-analysis and bioinformatics. The in vitro experiment determined the promoting effect of CELSR3 in the proliferation, invasion, and migration of HCC cells. CELSR3 knockout causes S-phage arrest in HCC cells. CELSR3 can also inhibit the apoptosis of HCC cells. The expression of the CELSR3 gene and protein was significantly elevated in HCC. Elevated CELSR3 was correlated to the bigger tumor size, higher pathological stage, and the worse overall survival of HCC. Methylation analysis revealed that the hypomethylation of CELSR3 regulated by DNMT1, DNMT3A, and DNMT3B may be the underlying mechanism of upregulated CELSR3. Biological enrichment analysis uncovered that the cell cycle, DNA replication, and PI3K-Akt signaling pathways were important pathways regulated by CELSR3 and its co-expressed genes in HCC. Taken together, upregulated CELSR3 is an important regulator in the progression and prognosis of HCC. The hypomethylation of CELSR3 and its regulation in the cell cycle may be the potential molecular mechanism in HCC.

LPCAT1 overexpression promotes the progression of hepatocellular carcinoma

“…RNA was reversely transcribed into cDNA using the 'Takara PrimeScript RT reagent' kit (Takara, Nanning, People's Republic of China, as we previously reported [26]. Betaactin (ACTB) was used as the internal reference gene (forward sequence: "5′-CAG GCA CCA GGG CGT GAT -3′"; reverse sequence: "5′-TAG CAA CGT ACA TGG CTG GG-3′") [27]. The primer of the target gene was designed on the mRNA sequence between the two gRNA binding sites (forward sequence: 5′-GTG ACC ATG ACG ATG TCC TCC-3′; reverse sequence: 5′-GTT CCC CAG ATC GGG ATG TC-3′).…”

Malignant Evaluation and Clinical Prognostic Values of M6A RNA Methylation Regulators in Prostate Cancer

“…Luo discovers that RBFOX3 promotes cell division and invasion, and improves migratory ability in gastric cancer [46]. In addition to the above-mentioned genes, other genes play some roles in the progression and prognosis of tumors, such as CELSR3 in hepatocellular carcinoma [47], CCDC144NL in gastric cancer [48], RPE65 in nonmelanocytic skin tumor [49], SLC27A4 in lung cancer [50], MEX3A in bladder urothelial carcinoma [51], CAPN12 in laryngeal cancer [52] and SLC4A4 in breast cancer [53]. In a word, the functional roles and underlying mechanisms of 11 eligible DE genes in the signature, and their association with m6A methylation regulators in PCa are still need further researches.…”

Integrative Analysis of Epigenome and Transcriptome Data Reveals Aberrantly Methylated Promoters and Enhancers in Hepatocellular Carcinoma

“…In our findings, 181 of those 661 high-confidence DMR-DEGs displayed a positive correlation between methylation and gene expression, and 48 of these 181 genes represented the same non-classical association in the TCGA-LIHC cohort. These 48 genes also contained several noted HCC-relevant genes, such as CELSR3 ( 124 ) and PCK1 ( 125 ), as well as some genes involved in other cancers, such as NTF3 in breast cancer ( 126 ) and TIMD4 in B-cell lymphoma ( 127 ).…”