Association of VLA4, 5, 6 and PSGL1 expression levels with engraftment in autologous HPSC transplantation in multiple myeloma patients.

The most promising therapy for leukemia is hematopoietic stem cell transplantation. Engraftment of HPSCs mainly depends on some factors such as adhesion molecules, including VLAs. This study tried to delineate the relationship between HPSCs engraftment and expression level of PSGL1 and VLA4, 5, and 6 genes in candidate MM patients for autologous bone marrow transplantation. Firstly, the CD 34+ HPSCs were collected from multiple myeloma (MM) patients after five days of G-CSF therapy through apheresis processes. Then, the patients were categorized into two groups of good and bad prognosis depending on engraftment time (Less or more than 18 days). Followingly, the expression of PSGL1 and VLA4, VLA5, and VLA6 genes were assessed by the qRT-PCR technique in each patient. Finally, the correlation between the genes and engraftment time was investigated to determine the prognostic role of each gene on HPSCs transplantation. Our findings demonstrated that there is a significant correlation between VLA4 (P=< 0.0001) and 5 (P = 0.005) levels and HPSCs engraftment time. As the higher levels of VLA4 and 5, the shorter time HPSCs engraftment occurs. In contrast, there was no significant correlation between VLA6 (P = 0.2) and PSGL1 (P = 0.3) genes levels and engraftment time. So that, the patients with a good prognosis had a higher level of VLA4 and VLA5, but no relation was found between VLA6 and PSGL1. It is concluded that VLA4 and VLA5 expression could be considered a significant prognostic factor for HPSC transplantation.

Long non-coding RNAs and microorganism-associated cancers.

Cancerous cells are abnormal cells characterized by aberrant growth and proliferation, which can involve various types of cells and tissues. Through numerous signalling pathways, many mechanisms are involved in cells that keep them normal. These signalling pathways are tightly set by different proteins whose expression is regulated by a large number of factors. In other words, when a regulating factor does not act properly or undergoes a change in its function or expression, the result will be that the subordinate gene and subsequently the related protein will show deranged expression and activity. This leads to disordered signalling pathways which bring about uncontrolled proliferation in cells. One of the most significant factors in adjusting the expression of genes is noncoding RNAs. It should be noted that all underlying causes initiating malignancy try to alter the main regulatory factors in cellular processes and gene expression and direct the cell to an unregulated state. Microorganisms have been identified as one of the important elements to direct normal cells to abnormality. That is, they probably agitate the malignant traits through manipulating significant factors such as ncRNAs in given cells using their own or host-related factors. The present study is aimed at examining how the long noncoding RNAs are involved in microorganism-mediated cancers.

Indirect Tumor Inhibitory Effects of MicroRNA-124 through Targeting EZH2 in The Multiple Myeloma Cell Line.

OBJECTIVE: Multiple myeloma (MM) is an incurable plasma cell malignancy. Several genetic and epigenetic changes affect numerous critical genes expression status in this disorder. CDKN2A gene is expressed at low level in almost all cases with MM disease. The mechanism of this gene down-regulation has remained controversial. In the present study, we targeted EZH2 by microRNA-124 (miR-124) in L-363 cells and assessed following possible impact on CDKN2A gene expression and phenotypic changes. MATERIALS AND METHODS: In this experimental study, growth inhibitory effects of miR-124 were measured by MTT assay in L-363 cell line. Likewise, cell cycle assay was measured by flowcytometery. The expression levels of EZH2 and CDKN2A were evaluated by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: qRT-PCR results showed induction of EZH2 gene expression after transduction of cells with lentivector expressing miR-124. The expression of CDKN2A was also upregulated as the result of EZH2 supression. Coincide with gene expression changes, cell cycle analysis by flow-cytometry indicated slightly increased G1-arrest in miRtransduced cells (P<0.05). MTT assay results also showed a significant decrease in viability and proliferation of miRtransduced cells (P<0.05). CONCLUSION: It seems that assembling of H3K27me3 mark mediated by EZH2 is one of the key mechanisms of suppressing CDKN2A gene expression in MM disease. However, this suppressive function is applied by a multi-factor mechanism. In other words, targeting EZH2, as the core functional subunit of PRC2 complex, can increase expression of the downstream suppressive genes. Consequently, by increasing expression of tumor suppressor genes, myeloma cells are stopped from aberrant expansions and they become susceptible to regulated cellular death.

The importance of miRNAs and epigenetics in acute lymphoblastic leukemia prognosis.

Acute lymphoblastic leukemia (ALL), one of the most common malignant human disorders, originates in different important genetic lesions in T-cell or B-cell progenitors. ALL is a malignant lymphoid progenitor with peak prevalence in children (2-5 years). The rate of survival when one is suffering from ALL depends on various agents including the age of the patient, responses to anti-leukemic therapy, and cell biology. miRNAs and epigenetics are important regulatory factors in the expression of genes. miRNAs are noncoding RNA with inhibitory effectors on specific mRNA. Patterns of DNA methylation are profoundly changed in ALL by epigenetic mechanisms. The deciphering of miRNA and the epigenetic pathogenesis in ALL could revolutionize response to the therapy and outcome, and create an enormous promise for novel approaches to reduce the toxic side-effects of intensive leukemia. Hence, pathogenetic miRNAs and epigenetics leading to the initiation and the progression of ALL are summarized in this review.