Potential using of microRNA-34A in combination with paclitaxel in colorectal cancer cells

Background: MicroRNAs are small noncoding RNAs which modulate gene expression at different levels. It has been shown that downregulation of miR-34a occurs in varieties of cancers including colorectal cancer (CRC). In this study, we investigated the potential tumor inhibitory effects of miR-34a alone or in combination with paclitaxel in CRC cells. Materials and Methods: SW480 cells were transduced with lentiviral overexpressed miR-34a. First, using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, the effect of miR-34a induction alone or in combination with paclitaxel on the cell viability and cell proliferation were estimated. Then, the expression level of target genes was measured using quantitative reverse transcription-polymerase chain reaction analysis. Eventually, the role of miR-34a and paclitaxel on cell cycle were determined with flow cytometry. Results: Gene expression analysis showed that miR-34a downregulates the expression of BCL2 and SIRT1 genes at mRNA level. Furthermore, miR-34a has a potential to reduce cell viability and cell cycle arrest at G1 phase. Combination of paclitaxel with overexpression of miR-34a significantly decreased cell viability compared to cell treated with miR-34a or paclitaxel alone. Interestingly, a combination of miR-34a and paclitaxel arrested cell cycle at two phases. Conclusion: Our results suggested that combination therapy of miR-34a and paclitaxel could be considered as the potential treatment of CRC.

High prevalence of AZFb microdeletion in Iranian patients with idiopathic non-obstructive azoospermia.

Background & objectives: Genetic factors contribute about 10 per cent of male infertility. Among these, genes in azoospermia factor (AZF) region including AZFa, AZFb, AZFc and AZFd on the long arm of Y chromosome are considered most important for spermatogenesis. Deletions in these regions are thought to be involved in some cases of male infertility associated with azoospermia or oligozoospermia. We studied the incidence of AZF deletions among Iranian infertile men with idiopathic non-obstructive azoospermia. Methods: A total of 100 Iranian azoospermic infertile men were selected for the molecular study of Y chromosome microdeletions. The presence of 13 sequence tagged site (STS) markers from AZF region was investigated using multiplex polymerase chain reaction (M-PCR). One hundred fertile men were also studied as control group. Results: Twelve (12%) patients showed Y chromosome microdeletions and among these, deletion in AZFb region was the most frequent (66.67%) followed by AZFc (41.67%), AZFd (33.33%) and AZFa (8.33%), respectively. Interpretation & conclusions: Because of relatively high incidence of Y chromosome microdeletions among Iranian azoospermic patients, molecular screening may be advised to infertile men before using assisted reproductive treatments.

Karyotypic evolution: cytogenetics follow-up study in childhood acute lymphoblastic leukemia.

Forty seven children affected with acute lymphoblastic leukemia (ALL) were cytogenetically investigated at diagnosis and all through different stages of the disease (remission and relapse). A clonal karyotypic abnormality was found in 32% at diagnosis (mainly comprised of cALLa+). A hyperdiploid mode with chromosome counts ranging from 47-58, was found to be most prominent among cALLa+ patients. The most common numerical aberrations were gain of chromosomes 2, 5, and 21. The structural aberrations at diagnosis were found to be del(9)(p22), inv(9)(p11q13) and del(19)(p12). None of the children showed ph+ chromosome. A good prognosis was found in cALLa+ children with an abnormal karyotype at diagnosis and of these children, those who showed karyotypic instability, had a significantly longer first remission time. The karyotypic evolution through remission(s) and relapse(s) revealed the occurrence of structural alterations, including changes in chromosomes 3, 6, 9, 21 and 22. However, irrespective of the karyotypic clonal nature at diagnosis, chromosome 9 was the most commonly involved chromosome through the course of disease.