Cancer Biomarkers - Volume 33, issue 3

Authors: Cui, Mingxin | Qu, Fengzhi | Wang, Libing | Liu, Xiaogang | Yu, Jingkun | Tang, Zhaoyuan | Cheng, Daming

Article Type: Research Article

Abstract: Hepatocellular carcinoma (HCC) is a cancer with relatively high mortality, yet little attention has been devoted for related prognostic biomarkers. This study analyzed differential expression of m5C RNA methyltransferase-related genes in normal samples and tumors samples in TCGA-LIHC using Wilcoxon test. K-means consensus clustering analysis was implemented to subdivide samples. Independent prognostic factors were screened by univariate and multivariate Cox regression analyses. KEGG pathway enrichment analysis was performed on the screened independent prognostic factor using GSEA tools. qPCR was conducted to test mRNA expression of key m5C RNA methyltransferase-related genes in tissues and cells. There were 7 m5C RNA methyltransferase-related …genes (NOP2, NSUN4, etc.) differentially expressed in HCC tumor tissues. HCC samples were classified into 3 subgroups through clustering analysis according to the expression mode of m5C RNA methyltransferase-related genes. It was also discovered that patients in different subgroups presented significant differences in survival rate and distribution of grade. Additionally, NOP2, NSUN4 and NSUN5 expression notable varied in different grades. Through regression analyses combined with various clinical pathological factors, it was displayed that NSUN4 could work as an independent prognostic factor. KEGG analysis showed that NSUN4 mainly enriched in signaling pathways involved in ADHERENS JUNCTION, RNA DEGRADATION, MTOR SIGNALING PATHWAY, COMPLEMENT and COAGULATION CASCADES. As examined by qPCR, NSUN4 was conspicuously upregulated in HCC patient’s tissues and cells. Altogether, our study preliminarily developed a novel biomarker that could be independently used in prognosis of HCC, which may provide a new direction for the study of related molecular mechanism or treatment regimen. Show more

Keywords: m5C RNA methyltransferase, NSUN4, HCC, prognosis, biomarker

DOI: 10.3233/CBM-210154

Citation: Cancer Biomarkers, vol. 33, no. 3, pp. 389-400, 2022

Authors: Zhang, Bin | Jin, Zhou | Zhang, Hao

Article Type: Research Article

Abstract: BACKGROUND: The disorder of LINC01207 has a significant regulatory effect on cancers, nevertheless its role in non-small cell lung cancer (NSCLC) have not been illustrated. This study investigated the regulatory effect of LINC01207 on NSCLC and clarify its molecular mechanism. METHODS: Bioinformatics analysis was used to find the target lncRNA, miRNA and mRNA. LncBase and TargetScan databases predicted the relationship between LINC01207, miR-525-5p and ARHGAP11A. Dual-luciferase reporter gene assay and RNA binding protein immunoprecipitation assay were used to verify the binding relationship between genes. Fluorescence in situ hybridization assay was used to localize the expression of LINC01207 …in NSCLC tissue. qRT-PCR and Western blot assays were used to measure the expression of LINC01207, miR-525-5p and ARHGAP11A. CCK-8 assay, Transwell assay and flow cytometry assay were used to detect NSCLC cell abilities. Mouse xenograft models further determined the effect of LINC01207 on the growth of NSCLC in vivo . RESULTS: LINC01207 was up-regulated in NSCLC tissue and cells, which was mainly localized in the cytoplasm. LINC01207 knockdown could inhibit the proliferation, migration and invasion of cancer cells and induce cell apoptosis. In addition, silencing LINC01207 could suppress tumor growth in vivo . LINC01207 could sponge and inhibit the expression of miR-525-5p in NSCLC cells, and inhibiting LINC01207 and miR-525-5p simultaneously could reverse the effect of miR-525-5p on the progression of NSCLC cells. Further study on downstream target genes showed that miR-525-5p could restrain the expression of ARHGAP11A, and then affect the progression of NSCLC. LINC01207 acting as a competing endogenous RNA (ceRNA) could regulate the expression of ARHGAP11A by competitively binding with miR-525-5p. CONCLUSION: LINC01207 regulates the progression of NSCLC by regulating the miR-525-5p/ARHGAP11A axis as a ceRNA and plays a carcinogenic role. In conclusion, our study elucidates the mechanism of LINC01207 regulating the progression of NSCLC, and provides a new idea for the diagnosis and treatment of NSCLC guided by lncRNA. Show more

Keywords: Non-small cell lung cancer, LINC01207, miR-525-5p, ARHGAP11A, proliferation, migration, invasion

DOI: 10.3233/CBM-203197

Citation: Cancer Biomarkers, vol. 33, no. 3, pp. 401-414, 2022

Authors: Zhang, Zixi | Li, Xiao | Yan, Xueli | Qiu, He | Li, Gai | Guo, Xiaowen | Lu, Yan | Yang, Jingyi | Jiao, Min | Chen, Xue | Zhu, Shaojun | Dang, Chengxue | Wang, Weizhong | Chu, Dake

Article Type: Research Article

Abstract: BACKGROUND: The Notch signaling regulates numerous cell growth, differentiation, and death. However, the expression pattern of its ligand Delta-like 4 (DLL4) in tumors is still uncertain. OBJECTIVE: In the present study, we examined DLL4 expression in colorectal cancer as well as assessed its role as a prognostic indicator in the present study. METHODS: DLL4 expression was examined by immunohistochemistry in 289 surgically resected specimens of colorectal cancer and adjacent normal tissues. The relationship between DLL4 expression and clinicopathological characteristics was analyzed. The association of DLL4 expression with the patients’ overall survival rate was …assessed by Kaplan-Meier and Cox proportional-hazards regression. RESULTS: Increased DLL4 level was detected in colorectal cancer compared with that of normal tissues. Elevated DLL4 level in colorectal cancer was associated with increased body mass index of patients. Moreover, increased DLL4 level was also found to be correlated with tumor invasion, metastases and unfavorable clinical outcom of patients. CONCLUSIONS: DLL4 level is increased in colorectal cancer, especially in patients with increased body mass index, indicating potential involvement of obesity-related tumorigenesis and development. It might also serve as a novel molecular marker to predicate outcome of patients. Show more

Keywords: DLL4, colorectal cancer, immunohistochemistry, body mass index, prognosis

DOI: 10.3233/CBM-200986

Citation: Cancer Biomarkers, vol. 33, no. 3, pp. 415-422, 2022