Survival analysis and functional annotation of long non-coding RNAs in lung adenocarcinoma.

Long non-coding RNAs (lncRNAs) are a subclass of non-protein coding transcripts that are involved in several regulatory processes and are considered as potential biomarkers for almost all cancer types. This study aims to investigate the prognostic value of lncRNAs for lung adenocarcinoma (LUAD), the most prevalent subtype of lung cancer. To this end, the processed data of The Cancer Genome Atlas LUAD were retrieved from GEPIA and circlncRNAnet databases, matched with each other and integrated with the analysis results of a non-small cell lung cancer plasma RNA-Seq study. Then, the data were filtered in order to separate the differentially expressed lncRNAs that have a prognostic value for LUAD. Finally, the selected lncRNAs were functionally annotated using a bioinformatic and systems biology approach. Accordingly, we identified 19 lncRNAs as the novel LUAD prognostic lncRNAs. Also, based on our results, all 19 lncRNAs might be involved in lung cancer-related biological processes. Overall, we suggested several novel biomarkers and drug targets which could help early diagnosis, prognosis and treatment of LUAD patients.

Potential role of RAB6C-AS1 long noncoding RNA in different cancers.

BACKGROUND: Long noncoding RNAs (lncRNAs) refer to a group of non-protein-coding RNAs that are usually more than 200 nucleotides. These long transcripts play significant roles in diverse cellular processes, mostly through epigenetic mechanisms. Thus, dysregulation of lncRNAs is associated with various diseases, especially cancer. This study aims to investigate the probable roles of RAB6C-AS1 lncRNA in different cancers. METHODS: Real-time quantitative reverse transcription-polymerase chain reaction was applied for the analysis of RAB6C-AS1 lncRNA amplification in gastric cancer (GC) samples compared with normal ones. Also, several online and offline data sets and tools were used to analyze the relation between RAB6C-AS1 lncRNA and different cancers. RESULTS: The end result of our analyses indicated that RAB6C-AS1 was overexpressed in 40% of the investigated GC specimens. Also, the results demonstrated a true relation between RAB6C-AS1 overexpression and higher GC tumor grades. However, bioinformatic analyses showed that while RAB6C-AS1 possibly functions as an oncogene in some cancer types, including prostate and breast cancers, it might have a tumor suppressive function in some others including brain tumors. CONCLUSIONS: We found that RAB6C-AS1 lncRNA is mostly overexpressed in GC. Also, based on bioinformatic and systems biology analyses, RAB6C-AS1 might function either as an oncogenic factor or tumor suppressor in a tissue-specific manner. Thus, RAB6C-AS1 could be considered as a candidate biomarker for various malignancies, especially prostate and brain cancers. According to our results, RAB6C-AS1 has a notable prognostic value for patients with brain lower grade glioma.

The potential role of PHF6 as an oncogene: a genotranscriptomic/proteomic meta-analysis.

Epigenetic complexes control various pathways within the cells. Their abnormalities can be involved in the initiation and the progression of different types of cancer. Nucleosome remodeling and deacetylase (NuRD) is an epigenetic complex that comprises several subunits such as PHF6. Although PHF6 is reported as a tumor suppressor in some of the hematopoietic malignancies, its function is still challenging in other cancers. Our study aimed at investigating the role of PHF6 in different types of cancer. We conducted a meta-analysis of PHF6 in human cancers at genomic, transcriptomic, and proteomic levels. For this purpose, we acquired the data from several databases, and tried to statistically integrate and analyze the data in order to find the potential role of PHF6 in different tumors. The results demonstrated that although PHF6 has been previously known as a tumor suppressor gene, it was remarkably overexpressed in many cancer types such as breast and colorectal cancers. Notably, PHF6 was under-expressed in a few types of cancer, including esophageal tumors. Moreover, the results indicated that although the mutation rate of PHF6 is relatively low, it is mutated in some tumor types.  In addition, our data for 40 epigenetic genes showed that missense and nonsense mutations were associated with overexpression and under-expression, respectively. Our results suggest that PHF6 may function as an oncogenic factor in several types of cancer. We also hypothesize that PHF6 may also play its role in a tissue-specific manner. Our findings suggest further investigations regarding the exact role of PHF6 in tumor types.

Genomic rearrangement screening of the BRCA1 from seventy Iranian high-risk breast cancer families.

BACKGROUND: The second leading cause of cancer deaths in women is breast cancer. Germline mutations in susceptibility breast cancer gene BRCA1 increase the lifetime risk of breast cancer. Eighty-one large genomic rearrangements (LGRs) have been reported up to date in BRCA1 gene, and evaluation of these rearrangements helps with precise risk assessment in high-risk individuals. In this study, we have investigated LGRs in BRCA1 among Iranian high-risk breast cancer families. MATERIALS AND METHODS: Seventy patients with breast cancer who were identified negative for point mutations or small deletions/insertions of BRCA1 gene were selected. Deletions and duplications of BRCA1 gene were evaluated using multiplex ligation-dependent probe amplification (MLPA). RESULTS: Two deletions, deletion of exons 1A/1B-2 and exon 24, were detected in two patients with breast cancer. The former alteration was found in a woman with a strong family history of breast cancer while the latter one was detected in a woman with early onset of breast cancer. CONCLUSION: Although our data confirm that LGRs in BRCA1 comprise a relatively small proportion of mutations in hereditary breast cancer in the Iranian population, MLPA analysis might be considered for screening of LGRs in high-risk individuals. It is worth to note that our results are consistent with previous studies in various Asian and European countries.

Parallel use of pluripotent human stem cell lung and heart models provide new insights for treatment of SARS-CoV-2.

SARS-CoV-2 primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe COVID-19. To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR- Cas9 mediated knock-out of ACE2, we demonstrated that angiotensin converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but further processing in lung cells required TMPRSS2 while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems. One-sentence summary: Rational treatment strategies for SARS-CoV-2 derived from human PSC models.

Bioinformatic Analysis of Circadian Expression of Oncogenes and Tumor Suppressor Genes.

BACKGROUND: Circadian rhythms are physiological and behavioral cycles with a period of approximately 24 hours that control various functions including gene expression. Circadian disruption is associated with a variety of diseases, especially cancer. Although some of the oncogenes and tumor suppressor genes (TSGs) are known as clock-controlled genes (CCGs), the analysis and annotation of circadian expression of most human oncogenes and TSGs are still lacking. This study aims to investigate the circadian expression of a list of human oncogenes and TSGs. METHODS: A bioinformatic analysis was conducted on a gene library comprising 120 genes to investigate the circadian expression of human oncogenes and TSGs. To achieve this purpose, the genotranscriptomic data were retrieved from COSMIC and analyzed by R statistical software. Furthermore, the acquired data were analyzed at the transcriptomic and proteomic levels using several publicly available databases. Also, the significance of all analyses was confirmed statistically. RESULTS: Altogether, our results indicated that 7 human oncogenes/TSGs may be expressed and function in a circadian manner. These oncogenes/TSGs showed a circadian expression pattern at CircaDB database and associated with at least one of the circadian genes/CCGs based on both genotranscriptomic and correlation analyses. CONCLUSIONS: Although 4 of 7 finally outputted genes have been previously reported to be clock controlled, heretofore there is no report about the circadian expression of 3 other genes. Considering the importance of oncogenes/TSGs in the initiation and progression of cancer, further studies are suggested for the identification of exact circadian expression patterns of these 3 human oncogenes/TSGs.

Tissue Specific Expression Levels of Apoptosis Involved Genes Have Correlations with Codon and Amino Acid Usage.

Different mechanisms, including transcriptional and post transcriptional processes, regulate tissue specific expression of genes. In this study, we report differences in gene/protein compositional features between apoptosis involved genes selectively expressed in human tissues. We found some correlations between codon/amino acid usage and tissue specific expression level of genes. The findings can be significant for understanding the translational selection on these features. The selection may play an important role in the differentiation of human tissues and can be considered for future studies in diagnosis of some diseases such as cancer.

HOTAIR: an oncogenic long non-coding RNA in different cancers.

Long non-coding RNAs (lncRNAs) refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer cells, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 (PRC2). In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.