The pattern of gene copy number alteration (CNAs) in hepatocellular carcinoma: an in silico analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer that occurs predominantly in patients with previous liver conditions. In the absence of an ideal screening modality, HCC is usually diagnosed at an advanced stage. Recent studies show that loss or gain of genomic materials can activate the oncogenes or inactivate the tumor suppressor genes to predispose cells toward carcinogenesis. Here, we evaluated both the copy number alteration (CNA) and RNA sequencing data of 361 HCC samples in order to locate the frequently altered chromosomal regions and identify the affected genes. RESULTS: Our data show that the chr1q and chr8p are two hotspot regions for genomic amplifications and deletions respectively. Among the amplified genes, YY1AP1 (chr1q22) possessed the largest correlation between CNA and gene expression. Moreover, it showed a positive correlation between CNA and tumor grade. Regarding deleted genes, CHMP7 (chr8p21.3) possessed the largest correlation between CNA and gene expression. Protein products of both genes interact with other cellular proteins to carry out various functional roles. These include ASH1L, ZNF496, YY1, ZMYM4, CHMP4A, CHMP5, CHMP2A and CHMP3, some of which are well-known cancer-related genes. CONCLUSIONS: Our in-silico analysis demonstrates the importance of copy number alterations in the pathology of HCC. These findings open a door for future studies that evaluate our results by performing additional experiments.

Enhancing Catecholase Activity of a Recombinant Human Tyrosinase Through Multiple Strategies.

BACKGROUND: Tyrosinases are copper-containing enzymes that initiate the melanin synthesis. They catalyze the direct oxidation of L-tyrosine or L-DOPA into L-DOPAquinone. OBJECTIVES: In present study, we aimed to obtain a recombinant tyrosinase with enhanced catecholase activity through site-directed mutagenesis. MATERIALS AND METHODS: The coding sequence of human tyrosinase along with native signal sequence was cloned into pET-28a (+). BL-21 was used as expression host and recombinant protein was purified by Ni-NTA resins. Site-directed mutagenesis was performed on M374 residue to achieve four mutants: M374D, M374T, M374K and M374R. Chloride ions (Cl-) were removed from all solutions, and an extra amount of Cu2+ ions was added to recombinant tyrosinases by a novel technique during the purification process. Removal of Cl- ions and addition of extra Cu2+ ions tripled catecholase activity of the recombinant protein. Therefore, all mutants were obtained under similar conditions. RESULTS: Although all the mutants presented higher catecholase activity in comparison to the wild-type enzyme, a significant increase in catecholase activity of the M374D mutant was observed ‒ 13.2-fold. In silico modeling suggested that a de novo hydrogen bond occurs between side chain carboxyl oxygens of D374 and H367 in M374D. In the wild-type tyrosinase, the peptide oxygen atom of M374 is responsible for hydrogen bonding with H367. CONCLUSIONS: Our data suggests that M374D mutational variant has applications in different areas such as agriculture, industry, and medicine.

Long Noncoding RNAs in Colorectal Adenocarcinoma; an in silico Analysis.

Long noncoding RNAs (lncRNAs) are lengthy noncoding transcripts which are involved in critical signaling pathways including cell cycle and apoptosis so it is not surprising to see their altered expression in human tumors. Colorectal adenocarcinoma is one the most frequent malignancies worldwide. The role of lncRNAs in colorectal adenocarcinoma is not well understood. To study the significance of lncRNAs in colorectal adenocarcinoma, we retrieved 189 approved lncRNAs from HGNC. The genes were imported into the cBioPortal database for transcriptomic analyses. We queried all the samples from TCGA provisional colorectal adenocarcinoma with RNA-seq v2 data in our study and considered RNA dysregulation with Z-score: ±2. The lncRNA which was altered in most of the patients were considered as "significant lncRNA" for further analyses. We considered the association of candidate lncRNAs with clinicopathologic parameters of samples including tumor disease anatomic site, neoplasm histologic types, tumor stage and survival. We also compute the specificity of the significant lncRNAs expression in colorectal adenocarcinoma comparing with other human cancers in cancer portal. Our analysis showed that lncRNAs SNHG6, PVT1 and ZFAS1 allocated the maximum alteration among the colorectal cases. The expression of SNHG6 and ZFAS1 was more in rectal adenocarcinoma than the colon carcinoma while the PVT1 showed the same expression levels in both tissues. However, we found that upregulation of PVT1 has been reduced the overall survival in patients. Altogether these data showed SNHG6, PVT1 and ZFAS1, are promising candidates for experimental research on colorectal adenocarcinoma to discover novel biomarker for this prevalent cancer.

Long non-coding RNAs expression levels in diffuse large B-cell lymphoma: An in silico analysis.

Long non-coding RNAs (lncRNAs), are lengthy noncoding transcripts with pivotal roles in biological pathways including cell cycle, apoptosis and chromatin remodeling. Aberrant expression of lncRNAs has been strongly connected with tumor progression and metastasis. However, the prognostic significance of lncRNAs in diffuse large-B-cell lymphoma (DLBCL) remains unclear. In this study, the expression levels of 189 approved lncRNAs were considered in DLBCL patients using several different genomic and transcriptome datasets. The analyses showed that the lncRNA GAS5 allocated the maximum score of RNA dysregulation and can be considered as good choice in DLBCLs' researches.

Long Non-Coding RNA SNHG6 as a Potential Biomarker for Hepatocellular Carcinoma.

Long Non-coding RNAs (lncRNAs) refer to all non-protein coding transcripts longer than 200 nucleotides. Their critical roles in different biological pathways have been already well established. Altered expression of lncRNAs can be involved in the cancer initiation and/or progression. Since patients with hepatocellular carcinoma (HCC) are usually diagnosed in late stages, developing diagnostic methods seems to be essential. In this study, the expression levels of different lncRNAs were systematically analysed in different genomic and transcriptome datasets. The analyses showed that SNHG6 is among the lncRNAs with distinctive dysregulation of expression and copy number variation in HCC tumors compared with normal tissues. The results also suggest that the dysregulation of SNHG6 is highly cancer type specific. Through co-occurrence analyses, we found that SNHG6 and its related co-expressed genes on 8q are involved in the structural integrity of ribosome and translation. This comprehensive in silico analysis, provides a resource for investigating SNHG6 in hepatocellular carcinoma and lays the groundwork for design of next researches.