No abstract

T cell immunoglobulin and mucin domain 3 (TIM-3) expression on malignant cells has been reported in some leukemias. In myelodysplastic syndrome (MDS), increased TIM-3 expression on TH1 cells, regulatory T cells, CD8+ T cells, and hematopoietic stem cells (HSCs), which play a role in the proliferation of blasts and induction of immune escape, has been reported. In AML, several studies have reported overexpression of TIM-3 on leukemia stem cells (LSCs) but not on healthy HSCs. Overexpression of TIM-3 on exhausted CD4+ and CD8+ T cells and leukemic cells in CML, ALL, and CLL patients could be a prognostic risk factor for poor therapeutic response and relapse in patients. Currently, several TIM-3 inhibitors are used in clinical trials for leukemias, and some have shown encouraging response rates for MDS and AML treatment. For AML immunotherapy, blockade TIM-3 may have dual effects: directly inhibiting AML cell proliferation and restoring T cell function. However, blockade of PD-1 and TIM-3 fails to restore the function of exhausted CD8+ T cells in the early clinical stages of CLL, indicating that the effects of TIM-3 blockade may be different in AML and other leukemias. Thus, further studies are required to evaluate the efficacy of TIM-3 inhibitors in different types and stages of leukemia. In this review, we summarize the biological functions of TIM-3 and its contribution as it relates to leukemias. We also discuss the effects of TIM-3 blockade in hematological malignancies and clinical trials of TIM-3 for leukemia therapy.

Long intergenic noncoding RNA p21 was mapped on the human chromosome 6p21.2. Accordingly, it was firstly described by promoting the p53-dependent apoptosis in the mouse. Also, it is a new lncRNA playing some vital roles in the cell cycle, apoptosis, cell proliferation, tumorigenesis, invasion, metastasis, and angiogenesis. In this regard, it was shown that, lincRNA-p21 regulates these biological processes involved in carcinogenesis through various signaling pathways including Notch signaling, JAK2/STAT3, and AKT/mTOR pathways. Another mechanism by that lincRNA-p21 can affect these processes is a cross-talk with different miRNAs. In vitro and in vivo studies revealed dysregulation of lincRNA-p21 in various human cancers. In addition, emerging evidence demonstrated that, lincRNA-p21 can be considered as a potential prognostic and therapeutic biomarker in cancers. Also, lincRNA-p21 enhances the response to radiotherapy for colorectal cancer. However, the molecular mechanisms of lincRNA-p21 in carcinogenesis have not been fully elucidated so far. So, this review summarizes the function of lincRNA-p21, as a tumor suppressor factor in different biological processes implicated in cancers.

No abstract

Preeclampsia (PE) is a pregnancy-specific complication which is a major cause of maternal and fetal morbidity and mortality. Recent studies have shown the aberrant expression of microRNAs (miRNAs) in the placenta of patients with PE. Dicer1 is a key enzyme in the generation of small noncoding RNAs including miRNAs. The aim of this study is to investigate the relationship between maternal and placental Dicer1 rs3742330 polymorphism and placental Dicer1 mRNA expression in PE and normotensive pregnant women. The blood and placenta of PE pregnant and normotensive pregnant women were collected after delivery. Dicer1 rs3742330 polymorphism was genotyped using PCR-RFLP method. The mRNA expression levels were measured using quantitative real time PCR. The maternal Dicer1 rs3742330 polymorphism was not associated with PE or PE severity; however, the placental Dicer1 rs3742330 AG genotype was associated with two fold higher risk of PE and three fold higher risk of severe PE (P = 0.018 and P = 0.005, respectively). The relative mRNA expression of Dicer1 gene in the placenta did not differ between the two groups. In addition, the relative mRNA expression of Dicer1 gene was significantly lower in the placenta of women with rs3742330 AG+GG genotypes in the total population (P = 0.028) and PE women (P = 0.004), but not in the control group. In conclusion, there was a relationship between placental but not maternal Dicer1 rs3742330 polymorphism and PE. There was no difference in Dicer1 mRNA expression between the PE and control groups; however, it was significantly lower in the placenta of women with rs3742330 AG+GG genotypes.