scholarly journals An in silico integrative analysis of hepatocellular carcinoma omics databases shows the dual regulatory role of microRNAs either as tumor suppressors or as oncomirs

Author(s):  
Mahmoud M. Tolba ◽  
Bangli Soliman ◽  
Abdul Jabbar ◽  
HebaT'Allah Nasser ◽  
Mahmoud Elhefnawi

MicroRNAs are well known as short RNAs bases, 22 nucleotides, binding directly to 3'untranslated region (3'UTR) of the messenger RNA to repress their functions. Recently, microRNAs have been widely used as a therapeutic approach for various types of Cancer. MicroRNA is categorized into tumor suppressor and oncomirs. Tumor suppressor microRNAs can repress the pathologically causative oncogenes of the hallmarks of Cancer. However, based on the fact that miRNA has no proper fidelity to bind specific mRNAs due to binding to off-targets, it results in a kind of inverse biological activity. Here, we have executed an in-silico integrative analysis of GEO/TCGA-LIHC of genes/microRNAs expression analysis in HCC, including (446 HCC vs. 146 normal specimens for miRNAs expression ) ad 488 specimens for genes expression. It virtually shows that microRNAs could have an ability to target both oncogenes and tumor suppressor genes that contribute to its dual activity role as a tumor suppressor and oncomirs via miRNA-lncRNA-TFs-PPI Crosstalk. Seven resultant microRNAs show a putative dual role in HCC. It enhances our concluded suggestion of using combination therapy of tumor suppressor genes activators with microRNAs.

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Lu Qi ◽  
Yanqing Ding

Most tumor suppressor genes are commonly inactivated in the development of colorectal cancer (CRC). The activation of tumor suppressor genes may be beneficial to suppress the development and metastasis of CRC. This study analyzed genes expression and methylation levels in different stages of CRC. Genes with downregulated mRNA expression and upregulated methylation level in advanced CRC were screened as the potential tumor suppressor genes. After comparing the methylation level of screened genes, we found that MBD1 gene had downregulated mRNA expression and upregulated methylation levels in advanced CRC and continuously upregulated methylation level in the progression of CRC. Enrichment analysis revealed that genes expression in accordance with the elevated expression of MBD1 mainly located on chromosomes 17p13 and 17p12 and 8 tumor suppressor genes located on chromosome 17p13. Further enrichment analysis of transcription factor binding site identified that SP1 binding site had higher enrichment and could bind with MBD1. In conclusion, MBD1 may be a tumor suppressor gene in advanced CRC and affect the development and metastasis of CRC by regulating 8 tumor suppressor genes through binding with SP1.


Author(s):  
Marisol Miranda Galvis ◽  
Estela Kaminagakura ◽  
Alan Roger Santos-Silva ◽  
Felipe Paiva fonseca ◽  
Oslei P. Almeida ◽  
...  

2021 ◽  
Author(s):  
Arman Shahrisa ◽  
Maryam Tahmaseby ◽  
Hossein Ansari ◽  
Zahra Mohammadi ◽  
Vinicio Carloni ◽  
...  

Abstract Recent studies showed that genetic lost or gain in the genome can predispose cells toward malignancy. Hepatocellular carcinoma (HCC) is the most common type of liver cancer which occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Prognosis of HCC is strongly connected with diagnostic delay. To date, no ideal screening modality has been developed for HCC. Recent findings demonstrated that Copy number variation (CNVs) can lead to activation of oncogenes and inactivation of tumor suppressor genes in cancers. In this study, CNV profile of 361 HCC samples was evaluated to reveal the potent - chromosomal regions involved in the disease. The obtained data showed that the chr1q and chr8p were two hotspot regions for gene amplifications and deletions in studied samples respectively. In this research, YY1AP1 (Yin Yang-1 Associated Protein 1) on chr1q22 was the most amplified gene in HCC samples and showed the positive correlation with tumor grade. Deletion of CHMP7 (Charged Multivesicular Body Protein 7) on chr8p21.3 was another frequently observed CNV among HCC patients. Both genes were interacted with variety of well-known oncogenes and tumor suppressor genes including YY1 (Yin Yang 1), CCND1 (Cyclin D1), HDAC1 (Histone deacetylase 1), VHL (von Hippel-Lindau tumor suppressor), MAD2L2 (Mitotic Arrest Deficient 2 Like 2), CEBPA (CCAAT/enhancer-binding protein alpha), CHMP4A, CHMP5, CHMP2A, CHMP3 and ENSG00000249884 (RNF103-CHMP3 gene), all of them are well-known in carcinogenesis. Although this study was based on in silico evaluations, our findings can open a new window for researchers of HCC to focus on such candidate genes during experimental assays.


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