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Background Lung cancer remains one of the most lethal carcinomas worldwide because of its late diagnosis. One of the DNA modifications is methylation, one of the primary alterations of tumor development, consisting of fascinating indicators for cancer diagnosis. This study investigated ZMYND-8 and RARβ2 gene methylation in NSCLC as a new epigenetic tool. Methods First, to find out the potential diagnostic capability of ZMYND-8 and RARβ2 genes methylation, we entirely surfed DNA methylation microarrays from the Cancer Genome Atlas (TCGA) data of NSCLC samples. Additionally, we took advantage of using q-MSP in several pieces comprising NSCLC tumors and neighboring normal tissues; ZMYND-8 and RARβ2 genes methylation grades were acquired. Results Our finding displayed significant hypomethylation of ZMYND-8 and hypermethylation of RARβ2 in NSCLC samples compared to neighboring standard specimens, which significantly correlated with the clinical stage of malignancy. In addition, the incredible precision of ZMYND-8 and RARβ2 methylations as reliable cancer diagnosis indicators in NSCLC was confirmed, drawing the ROC curve analysis with an AUC value of 0.751 and 0.8676, respectively, for ZMYND-8 and RARβ2. Additional studies of other dominant cancer entities in TCGA displayed that RARβ2’s higher methylation degree and ZMYND-8 lower methylation degree are prevalent changes in tumor evolution which could be possibly considered as a potential diagnostic biomarkers for lung cancer. Conclusion Based on this study, ZMYND-8 and RARβ2 methylation are reliable biomarkers for lung cancer.

Background: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. A number of dysregulated microRNAs (miRNAs) have been linked to CRC progression and treatment response and are thought to be promising prognostic biomarkers for this cancer. microRNA-330 (miR-330-5p) has been reported to inhibit cell proliferation through suppressing thymidylate synthase (TYMS). In the current study, miR-330-5p, TYMS, and their interactions were investigated to evaluate their therapeutic and diagnostic value for CRC treatment. Methods: The expression levels of miR-330-5p and TYMS were evaluated in silico using TCGA datasets for CRC. Data validation was performed on a set of internal samples (100 pairs of CRC tumor specimens and adjacent non-cancerous samples) utilizing real-time PCR assay. The linkage between clinicopathological parameters and expression levels was also investigated. Results: TCGA results indicated that miR-330-5p and TYMS were significantly upregulated and downregulated in the CRC, respectively. Real-time PCR results confirmed that the expression of miR-330-5p was significantly upregulated in tumor tissues relative to marginal tissues (P = 0.0005), whereas TYMS expression was significantly downregulated (P = 0.0001). The transcript level of miR-330-5p was associated with tumor stage and lymph node metastases. Conclusion: The microRNA-330 inhibited cell proliferation by suppressing thymidylate synthase (TYMS) in colorectal cancer. Therefore, suggesting that they are valuable factors for further studies of alternative treatment and diagnostic methods. © 2021, Springer Science+Business Media, LLC, part of Springer Nature., This study was supported by a grant from the research deputy of the Department of Tuberculosis and Lung Diseases Research Center, University Tabriz University of Medical Sciences, Tabriz, Iran.

The vascular endothelial growth factor (VEGF) signaling pathway has a crucial role in regulating tumor angiogenesis. VEGF-A shows prominent interaction with the VEGF receptor-1 and VEGF receptor-2 on the membrane of the endothelial cells. The current study aimed to design and model an anti-VEGF peptide based on VEGFR2 binding regions. The effective amino acid sequences in the interaction of VEGF-A and VEGFR-2 were investigated using Chimera, SPDBV and PyMOL software. The VEGF binding sites on the receptor were determined and used as the basis for peptide design. This sequence was then subjected to random mutagenesis, and the binding affinity of resultant peptides analyzed by Hex 8.0.0 and ClusPro software. Then, GROMACS v5.0.6 has been used for Molecular Dynamics (MD) simulation and assessing the stability of target-ligand complexes. Finally, the chosen peptide with the highest affinity was grafted into two loops of SFTI-1 (sunflower trypsin inhibitor-1) and MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II) frameworks for improving the peptide stability. Among the 18 peptides from the second library, four peptides were opted, of which NGIDFNRDKFLFL showed the highest affinity with a total energy of − 742 kcal/mol. We found that this peptide can bond to the VEGF and block VEGF binding to VEGFR2. The RMSD, RMSF, and H-bonds analysis verified the docking results. The peptide grafted into loop 1 of SFTI-1 increased the peptide-VEGF binding affinity compared to peptide alone. The results showed that in silico design could be used for the identification of efficient anti-angiogenic peptides for potential application in antiangiogenic therapies.

Colorectal cancer (CRC) is one of the most lethal and prevalent cancers throughout the world. Despite the remarkable advance in the field, drug resistance still remains as an unresolved problem in cancer. Hence, finding effective compounds with minimal side effects to fight cancer is of central priority. Herbal products have been traditionally used to prevent and treat a variety of diseases. In the present study, the antitumor effect of Terminalia catappa plant ethanolic extract (TCE) was assessed on SW480 CRC model cell line. In this regard, effects of TCE were evaluated on the proliferation, apoptosis, and migration of SW480 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V/PI flow cytometry, and scratch tests, respectively. Furthermore, changes in the expression of genes involved in these events including Bax, Bcl-2, Caspase 3, Caspase 8, Caspase 9, MMP-13, miR-21, and miR-34a were measured by quantitative real-time PCR (qRT-PCR). According to the MTT results, TCE reduced the proliferation of SW480 cells significantly. The flow cytometry test also revealed a notable rate of apoptosis induction after TCE treatment. An inhibitory effect on cell migration was also evident in scratch test. Expression patterns of the assessed genes also changed subsequent to TCE treatment. The results of this study indicated that T. catappa could be considered as a potential source of anticancer compounds and a candidate for further investigations.

Background Chinese hamster ovary (CHO) cells are the most commonly used mammalian host cell in the commercial-scale production of biopharmaceutical proteins. Modification of genes involved in apoptosis may improve the productivity of CHO cells. Executive caspases, including caspases 3 and 7, play critical roles in apoptosis. The effects of the ablation of the caspase 7 gene on proliferation and viability of CHO cells remains unknown. In this study, we applied clustered regularly interspaced short palindromic repeat (CRISPR/Cas9) to target caspase 7 gene of CHO K1 cell via all in one and homology targeted integration strategies. Consequently, the effect of caspase 7 deficiency on cell proliferation, viability, and apoptosis was studied by MTT assay and flow cytometry. Results Findings of gel electrophoresis, western blotting, and sequencing confirmed the caspase 7 gene silencing in CHO cells (CHO-KO). Proliferation assay revealed that caspase 7 deficiency in CHO cells resulted in the reduction of proliferation in various CHO-KO clones. Besides, the disruption of caspase 7 had negative effects on cell viability in exposure with NaBu which confirmed by MTT assay. Results of flow cytometry using Anexin V/PI demonstrated that Nabu treatment (11 mM) declined the percentage of live CHO-K1 and CHO-KO cells to 70.3% and 5.79%. These results verified that the CHO-K1 cells were more resistant to apoptosis than CHO-KO, however most of CHO-KO cells undergone early apoptosis (91.9%) which seems to be a fascinating finding. Conclusion These results reveal that caspase 7 may be involved in the cell cycle progression of CHO cells. Furthermore, it seems that targeting caspase 7 is not the ideal route as it had previously been imagined within the prevention of apoptosis but the relation between caspase 7 deficiency, cell cycle arrest, and the occurrence of early apoptosis will require more investigation.