MicroRNAs (miRNAs) are a group of noncoding RNA molecules of 20-23 nucleotides length that negatively regulate gene expressions in numerous cellular processes. Through complementary paring with target mRNAs, miRNAs have frequently emerged as dual regulators of cancer development by acting on multiple signaling pathways, thereby act as novel biomarkers for cancer diagnosis, prognosis, and prediction of response to treatment. As one of them, miR-30a has been found to act as an onco-suppressor of tumorigenesis pathways through inhibition of cellular proliferation, migration and invasion. Simultaneously, miR-30a plays a progressing role in several types of cancer, determined by relevant target genes as well. In the present review, we summarize recent research regarding miR-30a, including its biological function, expression and regulation, especially focusing on its role in cancer development and progression. Clinically, miR-30a may serve as a potential target in the diagnosis and therapy of human cancer.

/pdf/the-versatile-role-of-microrna-30a-in-human-cancer-l2fulfkxas.pdf

The Versatile Role of microRNA-30a in Human Cancer

miR-17-92 cluster microRNAs confers tumorigenicity in multiple myeloma

Pluripotent stem cells differentiate into almost any specialized adult cell type of an organism. PSCs can be derived either from the inner cell mass of a blastocyst-giving rise to embryonic stem cells-or after reprogramming of somatic terminally differentiated cells to obtain ES-like cells, named induced pluripotent stem cells. The potential use of these cells in the clinic, for investigating in vitro early embryonic development or for screening the effects of new drugs or xenobiotics, depends on capability to maintain their genome integrity during prolonged culture and differentiation. Both human and mouse PSCs are prone to genomic and (epi)genetic instability during in vitro culture, a feature that seriously limits their real potential use. Culture-induced variations of specific chromosomes or genes, are almost all unpredictable and, as a whole, differ among independent cell lines. They may arise at different culture passages, suggesting the absence of a safe passage number maintaining genome integrity and rendering the control of genomic stability mandatory since the very early culture passages. The present review highlights the urgency for further studies on the mechanisms involved in determining (epi)genetic and chromosome instability, exploiting the knowledge acquired earlier on other cell types.

Achilles' heel of pluripotent stem cells: genetic, genomic and epigenetic variations during prolonged culture.

The lipid kinase PI4KIIIβ and the eEF1A2 oncogene co-operate to disrupt three-dimensional in vitro acinar morphogenesis.

https://oaji.net/pdf.html?n=2014/109-1402987368.pdf

Association of Chromosomal Translocation and MiRNA Expression with The Pathogenesis of Multiple Myeloma

Conventional cytogenetic analysis is often hampered owing to the low mitotic index of multiple myeloma (MM) cells in bone marrow samples of MM. Interphase fluorescence in situ hybridization (I-FISH) analysis combined with magnetic-activated cell sorting (MACS) has substantially enhanced the sensitivity of cytogenetic analysis. Here, we used I-FISH to explore the incidence of chromosomal abnormalities in 60 Chinese patients with newly diagnosed MM. Five different specific probes for the regions containing 13q14.3 (D13S319), 14q32 (IGHC/IGHV), 1q21, 1p12, and 17p13 were used to detect chromosomal aberrations, and LSI IGH/CCND1, LSI IGH/FGFR3, and LSI IGH/MAF probes were further applied to detect t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in patients with 14q32 rearrangement. Fifty of the patients (83.3%) had at least one type of abnormalities regarding the regions analyzed. Nine patients (15%) had one abnormality; 10 patients (16.7%) had two abnormalities; 31 patients (51.7%) had three or more abnormalities. The most frequent abnormality in the patients was illegitimate IgH rearrangement (70%), followed by 13q14 deletion (63.3%), 1q21 amplification (61.7%), 1p12 deletion (33.3%), and 17p13 deletion (13.3%). These aberrations are not randomly distributed, but strongly interconnected. Patients with 17p13 deletion or t(4;14)(p16;q32) had significant higher β2-microglobulin level (P < 0.05). However, all these abnormalities had no correlation with age, gender, disease stage, and Ig isotype; yet, it was showed that the frequencies of the individual chromosomal abnormalities were very high. Taken together, MACS in combination with I-FISH may be a promising tool to detect the molecular cytogenetic abnormalities of MM.

Fluorescence in situ hybridization analysis of chromosome aberrations in 60 Chinese patients with multiple myeloma

Objective To investigate the expression of miR-21 and miR-30b in multiple myeloma (MM). Methods Peripheral blood mononuclear cells from patients with MM were cultured at 2.5 x 10(6) cells/ml in alpha-MEM supplemented with 10% of fetal bovine serum, antibiotics, RANKL (50 ng/ml), and macrophage colony-stimulating factor (25 ng/ml) for 10 to 14 days to obtain osteoclasts with bone-resorbing activity. Primary myeloma cells were purified from 12 MM patients. Of them, 8 samples were cocultured with osteoclasts and 4 as noncocultured control. The expression of miR-21 and miR-30b was detected by real-time PCR. Results The viability of MM cells recovered from cocultures was higher than those of noncocultured control. After cocultured with osteoclasts, primary myeloma cells from eight patients exhibited a 1.3- 5.9-fold increase in miR-21 expression and 1.38- 4.32-fold decrease in miR-30b expression compared with controls. In highly purified plasma cells from 3 healthy subjects, 12 MM patients and 11 MM cell lines, the expression of miR-21 was 1.9 +/- 0.8, 6.5 +/- 4.9 and 35.1 +/- 36.2, respectively; the expression of miR-30b was 13.6 +/- 1.8, 7.2 +/- 6.3 and 4.5 +/- 1.9, respectively. Conclusions miR-21 acts as an oncogene and miR-30b a tumor suppressor gene in MM.

[microRNA-21 and microRNA-30b expression in multiple myeloma.].

Multiple myeloma (MM) is characterized by complex genetic and chromosomal abnormalities involving both numerical and structural aberrations, which have clinical prognostic value. The plasma cell labeling index (PCLI) is one of the most important prognostic factors in newly diagnosed MM, and indicates plasma cell proliferative capacity. In this study, we determined the PCLI and the deletion of 13q14, retinoblastoma-1 gene (RB-1), 1p13, and 17p13, 1q21 amplification, and IgH rearrangements in 42 newly diagnosed patients with MM. A high PCLI was observed in 18 patients (42.9%), and the del(13q14) was present in 25 patients (59.5%), del(RB-1) in 23 patients (54.8%), del(17p13) in eight patients (19.1%), amp(1q21) in 23 patients (54.7%), del(1p13) in 17 patients (40.5%), and IgH rearrangements in 28 patients (66.7%). We further detected the IgH translocation partners: t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in 19, 15, and five patients, respectively. The PCLI had a significant correlation wi...

Plasma cell labeling index correlates with deletion of 13q14 in multiple myeloma.

Treatment of acute promyelocytic leukemia during pregnancy

OBJECTIVE To investigate the incidence of 1q21 amplification and 1p12 deletion, and analyze the correlation between these aberrations with disease progression, prognosis and outcome in patients with multiple myeloma (MM). METHODS Cytoplasm light chain immunofluorescence with simultaneous interphase fluorescence in situ hybridization (cIg-FISH) was used to detecte the 1q21 amplification and 1p12 deletion in 48 patients with MM. RESULTS 1q21 amplification (≥ 3 red signals) was determined in 26 of 48(54.2%) cases. The mortality of patients with 1q21 amplification was significantly higher than that of those lacking 1q21 amplification (P 0.05). There was a significant difference in D-S stage and mortality between patients with 3 and with 4 copies of 1q21 (P 0.05). 1p12 deletion (< 2 green signals) was found in 14 of 48 (29.2%) cases. There was no significant difference in sex, age, D-S stage, ISS stage, isotype, subgroup, and mortality between patients with and without 1p12 deletion. CONCLUSION The frequency of chromosome 1 aberrations in multiple myeloma is high and 1q21 amplification is a poor prognosis factor.

[Investigation of chromosome 1 aberrations in patients with multiple myeloma using cIg-FISH method and its significance].

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