MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-ß8.

It has been reported that the miR-106b∼25 cluster, a paralog of the miR-17∼92 cluster, possesses oncogenic activities. However, the precise role of each microRNA (miRNA) in the miR-106b∼25 cluster is not yet known. In this study, we examined the function of miR-93, one of the microRNAs within the miR-106b∼25 cluster, in angiogenesis and tumor formation. We found that miR-93 enhanced cell survival, promoted sphere formation and augmented tumor growth. Most strikingly, when miR-93-overexpressing U87 cells were co-cultured with endothelial cells, they supported endothelial cell spreading, growth, migration and tube formation. In vivo studies revealed that miR-93-expressing cells induced blood vessel formation, allowing blood vessels to extend to tumor tissues in high densities. Angiogenesis promoted by miR-93 in return facilitated cell survival, resulting in enhanced tumor growth. We further showed that integrin-ß8 is a target of miR-93. Higher levels of integrin-ß8 are associated with cell death in tumor mass and in human glioblastoma. Silencing of integrin-ß8 expression using small interfering RNA promoted cell proliferation, whereas ectopic expression of integrin-ß8 decreased cell growth. These findings showed that miR-93 promotes tumor growth and angiogenesis by suppressing, at least in part, integrin-ß8 expression. Our results suggest that inhibition of miR-93 function may be a feasible approach to suppress angiogenesis and tumor growth.

[Structural and functional changes of bone marrow stroma in chronic lymphocytic leukemia]. / Strukturnaia i funktsional'naia perestroika stromy kostnogo mozga pri khronicheskom limfotsitarnom lekoze.

Marrow stroma was investigated in 20 patients with chronic lymphocytic leukemia (CLL). Such morphological and functional features as adipose tissue reduction, sinusoid pattern obliteration and increased number of reticular cells were identified as typical of marrow stroma in such patients. Foci of fibrosis, nuclear bodies in stromal cell nuclei and heightened proliferation of stromal precursors in organ cultures were recorded in the subendostal and perivascular areas in 60% of patients with diffuse lesions of bone marrow. Bone marrow stroma was shown to suffer morphological and functional changes which were particularly pronounced in diffuse lesions of the bone marrow. Such changes may be traced both to the malignant clone of lymphoid cells and stromal lesions.

[Morphologic and functional features of hemopoietic microenvironment in acute lymphoblastic leukemia]. / Morfofunktsional'nye osobennosti krovetvornogo mikrookruzheniia pri ostrykh limfoblastnykh leikozakh.

Data of the histological, ultrastructural and culture cell investigations of bone marrow microenvironment in 20 patients with acute lymphoblastic leukemia (ALL) are presented. Morphological and functional peculiarities of the patients' bone marrow stroma different from that in healthy subjects were identified. They included distorted histotopographic patterns of stroma-hemopoietic cell-to-cell interaction, obliteration of sinusoid counts, resorption on the sites of internal bone support structures, a changed stromal cells ratio, formation of reticular cell clusters in the subendosteal and perivascular bone marrow areas, fibroid centers, the presence of nuclear bodies in stromal cell nuclei and an intensified proliferation of stromal cell precursors in organ tissue cultures. Morphological and functional changes in bone marrow microenvironment were detected in ALL patients, which could have been caused both by malignant cell clones and stromal defects.

[Morphologic features of bone marrow in myelodysplastic states]. / Morphologicheskie osobennosti stromy kostnogo mozga pri mielodisplasticheskikh sostoianniiakh.

The results of histological and ultrastructural studies of bone marrow hemopoietic microenvironment carried out in 27 patients with different myelodisplasias are presented. The following morphological peculiarities of bone marrow stromal tissue have been identified: abnormal localisation of immature hemopoietic cells, reticuline fibrosis, disorganized erythroid islands, and intranuclear virus-like pathologic inclusions in all stromal cells. The structure of nucleoli in endosteal and perivascular cells was changed. It was shown that morphofunctional changes in hemopoietic environment may lead to hemopoietic disorders.

[Various morphofunctional characteristics of hematopoietic tissue in preleukemic conditions]. / Nekotorye morfofunktsional'nye osobennosti gemopoéticheskoi tkani pri predleikoznykh sostoianiiakh.

Cultural, ultrastructural, cytochemical and histological investigations of bone marrow tissue were conducted in 26 patients with varying types of preleukemia states. A number of early structural, morphological and functional signs of hemopoietic disorders of different character and manifestation degree have been revealed. Particularly, a relationship has been established between the pathologic changes appearing in the bone marrow stroma and disorders in the morphological and functional state of the hemopoietic cells.