Metastasis-associated in colon cancer 1 (MACC1) has been established as an independent prognostic indicator of metastasis formation and metastasis-free survival for patients with colon cancer and other solid tumors. However, no data are available concerning MACC1 expression in human astrocytic tumors. Glioblastoma multiforme (GBM) is the most prevalent primary brain tumor of adulthood, and due to its invasive and rapid growth, patients have unfavorable prognoses. Although these tumors rarely metastasize, their invasive and migratory behavior is similar to those of metastatic cells of tumors of different origin. Thus, we hypothesized that MACC1 may be involved in progression of human gliomas. We performed real-time measurements of proliferation and migration in MACC1-transfected GBM cell lines (U138, U251) and evaluated tumor formation in organotypic hippocampal slice cultures of mice. Semiquantitative and quantitative real-time reverse transcription PCR analyses were performed for MACC1 and for its transcriptional target c-Met in human astrocytoma of World Health Organization grade II (low-grade astrocytoma) and GBM biopsies. Data were validated by MACC1 immunohistochemistry in independent matched samples of low-grade astrocytoma and GBM. MACC1 increases the proliferative, migratory, and tumor-formation abilities of GBM cells. The c-Met inhibitor crizotinib reduced MACC1-induced migration and tumor formation in organotypic hippocampal slice cultures of mice. Analyzing patients’ biopsies, MACC1 expression increased concomitantly with increasing World Health Organization grade. Moreover, MACC1 expression levels allowed discrimination of dormant and recurrent low-grade astrocytomas and of primary and secondary GBM. Strong MACC1 expression correlated with reduced patient survival. MACC1 may represent a promising biomarker for prognostication and a new target for treatment of human gliomas.

Circular RNAs (circRNAs) represent a type of endogenous noncoding RNA generated by back-splicing events. Unlike the majority of RNAs, circRNAs are covalently closed, without a 5 ′ end or a 3 ′ poly(A) tail. A few circRNAs can be associated with polysomes, suggesting a protein-coding potential. CircRNAs are not degraded by RNA exonucleases or ribonuclease R and are enriched in exosomes. Recent developments in experimental methods coupled with evolving bioinformatic approaches have accelerated functional investigation of circRNAs, which exhibit a stable structure, a long half-life, and tumor specificity and can be extracted from body fluids and used as potential biological markers for tumors. Moreover, circRNAs may regulate the occurrence and development of cancers and contribute to drug resistance through a variety of molecular mechanisms. Despite the identification of a growing number of circRNAs, their effects in hematological cancers remain largely unknown. Recent studies indicate that circRNAs could also originate from fusion genes (fusion circRNAs, f-circRNAs) next to chromosomal translocations, which are considered the primary cause of various cancers, notably hematological malignancies. This Review will focus on circRNAs and f-circRNAs in hematological cancers.

Neuroblastoma is the most common diagnosed tumor in infants and the second most common extracranial tumor of childhood. The survival rate of patients with high-risk neuroblastoma is still very low despite intensive multimodal treatments. Therefore, new treatment strategies are needed. In recent years, miRNA-based anticancer therapy has received growing attention. Advances in this novel treatment strategy strongly depends on the identification of candidate miRNAs with broad-spectrum antitumor activity. Here, we identify miR-193b as a miRNA with tumor suppressive properties. We show that miR-193b is expressed at low levels in neuroblastoma cell lines and primary tumor samples. Introduction of miR-193b mimics into nine neuroblastoma cell lines with distinct genetic characteristics significantly reduces cell growth in vitro independent of risk factors such as p53 functionality or MYCN amplification. Functionally, miR-193b induces a G1 cell cycle arrest and cell death in neuroblastoma cell lines by reducing the expression of MYCN, Cyclin D1 and MCL-1, three important oncogenes in neuroblastoma of which inhibition has shown promising results in preclinical testing. Therefore, we suggest that miR-193b may represent a new candidate for miRNA-based anticancer therapy in neuroblastoma.

Epigenetic silencing of miR-520c leads to induced S100A4 expression and its mediated colorectal cancer progression