During normal development of the vertebrate nervous system, large numbers of neurons in the central and peripheral nervous system undergo naturally occurring cell death. For example, about half of all spinal motor neurons die over a period of a few days in developing avian, rat and mouse embryos. Previous studies have shown that extracts from muscle and brain, secreted factors from glia, as well as several growth factors and neurotrophic agents, including muscle-derived factors, can promote the survival of developing motor neurons in vitro and in vivo. But because neurotrophins and other known trophic agents administered alone or in combination are insufficient to rescue all developing motor neurons from cell death, other neurotrophic molecules are probably essential for the survival and differentiation of motor neurons. Here we report that glial-cell-line-derived neurotrophic factor (GDNF), a potent neurotrophic factor that enhances survival of mammalian midbrain dopaminergic neurons, rescues developing avian motor neurons from natural programmed cell death in vivo and promotes the survival of enriched populations of cultured motor neurons. Furthermore, treatment with this agent in vivo also prevents the induced death and atrophy of both avian and mouse spinal motor neurons following peripheral axotomy.

1Somatic copy-number variations (CNV) may drive cancer progression through both coding and 2 noncoding transcripts. However, noncoding transcripts resulting from CNV are largely unknown, 3 especially for circular RNAs. By integrating bioinformatics analyses of alerted circRNAs and 4 focal CNV in lung adenocarcinoma (LAC), we identify a proto-oncogenic circular RNA 5 (circPRKCI) from the 3q26.2 amplicon, one of the most frequent genomic aberrations in multiple 6 cancers. circPRKCI was overexpressed in LAC tissues, in part due to amplification of the 3q26.2 7 locus, and promoted proliferation and tumorigenesis of LAC. circPRKCI functioned as a sponge 8 for both miR-545 and miR-589 and abrogated their suppression of the pro-tumorigenic 9 transcription factor E2F7. Intra-tumor injection of cholesterol-conjugated siRNA specifically 10 targeting circPRKCI inhibited tumor growth in a patient-derived LAC xenograft model. In 11 summary, circPRKCI is crucial for tumorigenesis and may serve as a potential therapeutic target in 12 LAC patients. 13

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and deadly types of cancer worldwide especially in Eastern Asia and the prognosis of ESCC remain poor. Recent evidence suggests that circular RNAs (circRNAs) play important roles in multiple diseases, including cancer. In this study, we characterized a novel circRNA termed hsa_circ_0067934 in ESCC tumor tissues and cell lines. We analyzed a cohort of 51 patients and found that hsa_circ_0067934 was significantly overexpressed in ESCC tissues compared with paired adjacent normal tissues. The high expression level of hsa_circ_0067934 was associated with poor differentiation (P = 0.025), I-II T stage (P = 0.04), and I-II TNM stage (P = 0.021). The in vitro silence of hsa_circ_0067934 by siRNA inhibited the proliferation and migration of ESCC cells and blocked cell cycle progression. Cell fraction analyses and fluorescence in situ hybridization detected that hsa_circ_0067934 was mostly located in the cytoplasm. Our findings suggest that hsa_circ_0067934 is upregulated in ESCC tumor tissue. Our data suggest that hsa_circ_0067934 represents a novel potential biomarker and therapeutic target of ESCC.