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Prostate cancer is worldwide the sixth leading cause of cancer related death in men thus early detection and successful treatment are still of major interest. The commonly performed screening of the prostate-specific antigen (PSA) is controversially discussed, as in many patients the prostate-specific antigen levels are chronically elevated in the absence of cancer. Due to the unsatisfying efficiency of available prostate cancer screening markers and the current treatment outcome of the aggressive hormone refractory prostate cancer, the evaluation of novel molecular markers and targets is considered an issue of high importance. MicroRNAs are relatively stable in body fluids orchestrating simultaneously the expression of many genes. These molecules are currently discussed to bear a greater diagnostic potential than protein-coding genes, being additionally promising therapeutic drugs and/or targets. Herein we review the potential impact of the microRNAlet-7family on prostate cancer and show how deregulation of several of its target genes could influence the cellular equilibrium in the prostate gland, promoting cancer development as they do in a variety of other human malignant neoplasias.

Individual cancer cells carry a bewildering number of distinct genomic alterations i.e., copy number variations and mutations, making it a challenge to uncover genomic-driven mechanisms governing tumorigenesis. Here we performed exome-sequencing on several breast cancer cell lines which represent two subtypes, luminal and basal. We integrated this sequencing data, and functional RNAi screening data (i.e., for identifying genes which are essential for cell proliferation and survival), onto a human signaling network. Two subtype-specific networks were identified, which potentially represent core-signaling mechanisms underlying tumorigenesis. Within both networks, we found that genes were differentially affected in different cell lines; i.e., in some cell lines a gene was identified through RNAi screening whereas in others it was genomically altered. Interestingly, we found that highly connected network genes could be used to correctly classify breast tumors into subtypes based on genomic alterations. Further, the networks effectively predicted subtype-specific drug targets, which were experimentally validated., 4 figs, more related papers at http://www.cancer-systemsbiology.org, appears in Cell Reports, 2013

The dysregulation of miRNA expression has frequently been observed in breast cancer. Therefore, we investigated the expression profile of miRNAs that may be associated with expression of the FHIT gene in breast cancer and assessed their clinicopathological significance. The expression levels of miR-143, miR-663a, miR-668, miR-922 and FHIT were analyzed in normal and malignant breast tissues from 65 patients with breast cancer. We studied the correlation between the expression of miR-143, miR-663a, miR-668, miR-922 and FHIT and the clinicopathological features presented by the patients. The expression levels of the miRNAs and FHIT were downregulated in breast cancer tissue. The expression levels of miR-143, miR-663a and miR-668 were significantly reduced in FHIT downregulated tumors. miR-668 expression was also significantly altered relative to FHIT down- and up- regulated tumor tissues. Reduced miR-663a expression was statistically associated with high-grade ER/PR (+) status, benign reactive hyperplasia, lymph-node metastasis, in-situ component >25% and Ki 67 > 15% compared with non-tumor tissues. Additionally, reduced miR-668 expression was significantly different between tumors with and without lymph-node metastasis. miR-668 may play an important role in breast cancer development and progression by regulating the expression of FHIT. Furthermore, miR-668 and miR-663a may be potential prognostic biomarkers for breast cancer.

Initiation, progression and evasion are sequential steps in cancer formation, with autonomous cell proliferation as a final outcome. Genetic or epigenetic alterations of key regulatory genes of the cell cycle are frequently associated with these phenomena. Recently, chromosomal instability, a long-supposed driving force of tumorigenesis, was associated with dysregulation of mitotic genes, providing advantages to tumor cells. Numerous molecules thus provide a key link in the chain of relationships between chromosomal instability and cancer. Here, we discuss emerging evidence revealing that two p53 family members, p53 and p73, might be key regulatory genes at the heart of the relationship between chromosomal instability and cancer. We argue that the role of members of the p53 family as tumor suppressor proteins, their impact on the control of cellular ploidy, and their newly emerging connection with mitotic checkpoint regulatory genes support the suggestion that p73 and p53 could be two of the missing links among chromosomal instability, the mitotic checkpoint and cancer.

Aims: Up-regulated gene 4 (URG4) is a novel gene that may be associated with the onset of tumorigenesis and cell cycle regulation. The present study examined for the first time the expression of URG4 in osteosarcoma, which is one of the most rapidly growing sarcomas, and investigated its prognostic value in both disease-free and overall survival of the patients. Methods: The expression of URG4 in osteosarcoma tissues was examined by immunohistochemistry in 46 patients who underwent surgical operation for osteosarcoma; the correlation of URG4 with proliferating cell nuclear antigen index (PCNA) and microvessel count (MVC) was analysed, and the prognostic value of URG4 in patients was investigated. Results: URG4 was highly expressed in 40 of 46 (86.96%) osteosarcoma specimens with cytoplasmic staining, and also increased in the specimens with recurrence (p < 0.05) and metastasis (p < 0.05). The mean disease-free survival and overall survival were 50.25 and 54.08 months for patients with over-expressed URG4, compared with 69.54 and 70.01 months for those with low expression. URG4 was also found to be highly related with PCNA, while no significant relationship was found between URG4 and MVC. Conclusions: URG4 may play important roles in the development of osteosarcoma, and might be a useful molecular marker for predicting the prognosis of osteosarcoma. © 2009 Royal College of Pathologists of Australasia.