ZNF677 downregulation by promoter hypermethylation as a driver event through gastric tumorigenesis.

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide, due to poor prognosis and treatment failure; demanding new diagnostic and therapeutic targets. Therefore, in the present study, the methylation and expression status of ZNF677, as a promising tumor suppressor, were investigated in GC. Gene Expression Omnibus (GEO) datasets were used to initially evaluate ZNF677 expression and methylation in GC samples. Confirmation was performed on fifty internal samples, including gastric tumors and adjacent normal specimens, using q-MSP and q-PCR methods. Further validations were done using The Cancer Genome Atlas (TCGA) data on human cancers. The obtained results in silico and experimentally illustrated that ZNF677 is significantly hypermethylated and downregulated through gastric tumorigenesis. ZNF677 methylation levels were also correlated with perineural invasion (p = 0.0382) in internal samples. Furthermore, Spearman's correlation analysis showed that ZNF677 methylation is negatively (r = -0.4614, p < 0.0001) correlated with its mRNA expression levels. ROC curve analysis also illustrated the high diagnostic value of ZNF677 methylation for early detection of GC (AUC = 0.8592). Gene set enrichment analysis further revealed that ZNF677 participates in the regulation of cellular processes such as cell proliferation in GC. Moreover, in addition to hypermethylation in other malignancies, including breast, lung, and colorectal cancers, ZNF677 was hypermethylated in precancerous gastric tissues with intestinal metaplasia, indicating its methylation as a driver event through tumorigenesis. Taken together, our results suggest ZNF677 as a potential tumor suppressor gene, which could be considered as a diagnostic and therapeutic target for GC.

Strategies in DNA vaccine for melanoma cancer.

According to reports of the international agency for cancer on research, although malignant melanoma shows less prevalence than nonmelanoma skin cancers, it is the major cause of skin cancer mortality. Given that, the production of effective vaccines to control melanoma is eminently required. In this regard, DNA-based vaccines have been extensively investigated for melanoma therapy. DNA vaccines are capable of inducing both cellular and humoral branches of immune responses. These vaccines possess some valuable advantages such as lack of severe side effects and high stability compared to conventional vaccination methods. The ongoing studies are focused on novel strategies in the development of DNA vaccines encoding artificial polyepitope immunogens based on the multiple melanoma antigens, the inclusion of molecular adjuvants to increase the level of immune responses, and the improvement of delivery approaches. In this review, we have outlined the recent advances in the field of melanoma DNA vaccines and described their implications in clinical trials as a strong strategy in the prevention and control of melanoma.

microRNA-181a mediates the chemo-sensitivity of glioblastoma to carmustine and regulates cell proliferation, migration, and apoptosis.

Glioblastoma multiform (GBM) as the most frequent and lethal brain tumor is defined by aggressive invasiveness and considerable resistance to chemotherapy. The molecular mechanisms underlying GBM tumorigenesis still needs to be further investigated. Considering that, the current study was aimed to investigate the function of miR-181a in human glioblastoma cells in combination with carmustine. U373 cell line with the low expression levels of miR-181a was selected for functional investigations. MTT assay was used to determine cell viability and Annexin V/PI and DAPI staining were employed to evaluate apoptosis induction. Also, cell migration and cell cycle progression were investigated using wound healing test and flow cytometry, respectively. qRT-PCR was used for the quantification of gene expression. MTT assay results revealed that miR-181a replacement increased the sensitivity of U373 cells to low doses of carmustine. Moreover, miR-181a was shown to increase the sub G1 cell cycle arrest and apoptosis induction by carmustine via regulating the expression of related genes including caspase-9, Bcl-2, and SIRT1. Furthermore, this miRNA combined with carmustine suppressed cell migration via downregulation of MMP-2 and Bach1 and reduced the clonogenic ability of U373 cells. Additionally, miR-181a-mediated downregulation of AKT1 implied that this miRNA could inhibit cell proliferation by modulating PI3K/AKT signaling pathway. In conclusion, the findings of this study suggest that miR-181a replacement, regarding its tumor-suppressive effects and sensitization of glioblastoma cells to carmustine, could be considered as a potential therapeutic strategy to improve the efficiency of glioblastoma chemotherapy.

microRNA-181 serves as a dual-role regulator in the development of human cancers.

MicroRNAs (miRNAs) as the regulatory short noncoding RNAs are involved in a wide array of cellular and molecular processes. They negatively regulate gene expression and their dysfunction is correlated with cancer development through modulation of multiple signaling pathways. Therefore, these molecules could be considered as novel biomarkers and therapeutic targets for more effective management of human cancers. Recent studies have demonstrated that the miR-181 family is dysregulated in various tumor tissues and plays a pivotal role in carcinogenesis. They have been shown to act as oncomirs or tumor suppressors considering their mRNA targets and to be involved in cell proliferation, apoptosis, autophagy, angiogenesis and drug resistance. Additionally, these miRNAs have been demonstrated to exert their regulatory effects through modulating multiple signaling pathways including PI3K/AKT, MAPK, TGF-b, Wnt, NF-κB, Notch pathways. Given that, in this review, we briefly summarise the recent studies that have focused on the roles of miRNA-181 family as the multifunctional miRNAs in tumorigenesis and cancer development. These miRNAs may serve as diagnostic and prognostic biomarkers or therapeutic targets in human cancer gene therapy.

MicroRNA-193a and taxol combination: A new strategy for treatment of colorectal cancer.

Micro RNAs (miRNAs) show a considerable promise as a therapeutic agent for combination therapy of colorectal cancer (CRC). Given that, the current study was purposed to explore the potential therapeutic role and underlying mechanism of miR-193a as a promising tumor suppressor in human CRC cell lines in combination with Taxol. Therefore, HT-29 cells with the lowest expression levels of miR-193a were treated with miR-193a mimics and Taxol, separately or in combination. Functional analyses showed that the combination therapy inhibited migration and colony formation of HT-29 cells and arrested the cell cycle at the G1 phase. Moreover, treatment with Taxol reduced cell survival with an increase in mRNA expression of metastasis-related genes caspase-3 and caspase-9, whereas miR-193a transfection alone didn't significantly influence cell viability and apoptosis induction. Quantitative reverse transcription polymerase chain reaction results also revealed that miR-193a replacement decreased the expression levels of c-Myc, MMP-9, vimentin, and ROCK in treatment groups compared to the controls. Therefore, it could be concluded miR-193a inactivates cell migration via suppression of metastasis pathways in CRC and through downregulation of c-Myc, acts as a negative regulator of cell cycle and growth. Then, our findings imply that miR-193a replacement combined with Taxol chemotherapy could be considered as a new potential therapeutic approach for improvement of CRC treatment.

Comparison of DNA and mRNA vaccines against cancer.

Nucleic acid vaccines (NAVs) have recently been tested as a cancer therapy. DNA and mRNA vaccines deliver genetic information encoding tumor antigens (TAs) to the host, which then produces immune responses against cancer cells that express the TAs. Although NAVs are easy, safe, and simple to manufacture, they have not so far been considered viable alternatives to peptide vaccines. Choosing the right TAs, insufficient immunogenicity, and the immunosuppressive nature of cancer are some challenges to this approach. In this review, we discuss approaches that been used to improve the efficiency of anticancer NAVs.

Recent advances on HIV DNA vaccines development: Stepwise improvements to clinical trials.

According to WHO (World Health Organization) reports, more than 770,000 people died from HIV and almost 1.7 million people becoming newly infected in the worldwide in 2018. Therefore, many attempts should be done to produce a forceful vaccine to control the AIDS. DNA-based vaccines have been investigated for HIV vaccination by researches during the recent 20 years. The DNA vaccines are novel approach for induction of both type of immune responses (cellular and humoral) in the host cells and have many advantages including high stability, fast and easy of fabrication and absence of severe side effects when compared with other vaccination methods. Recent studies have been focused on vaccine design, immune responses and on the use of adjuvants as a promising strategy for increased level of responses, delivery approaches by viral and non-viral methods and vector design for different antigens of HIV virus. In this review, we outlined the aforementioned advances on HIV DNA vaccines. Then we described the future trends in clinical trials as a strong strategy even in healthy volunteers and the potential developments in control and prevention of HIV.