Evidence that offspring traits can be shaped by parental life experiences in an epigenetically inherited manner paves a way for understanding the etiology of depression. Here, we show that F1 offspring born to F0 males of depression-like model are susceptible to depression-like symptoms at the molecular, neuronal, and behavioral levels. Sperm small RNAs, and microRNAs (miRNAs) in particular, exhibit distinct expression profiles in F0 males of depression-like model and recapitulate paternal depressive-like phenotypes in F1 offspring. Neutralization of the abnormal miRNAs in zygotes by antisense strands rescues the acquired depressive-like phenotypes in F1 offspring born to F0 males of depression-like model. Mechanistically, sperm miRNAs reshape early embryonic transcriptional profiles in the core neuronal circuits toward depression-like phenotypes. Overall, the findings reveal a causal role of sperm miRNAs in the inheritance of depression and provide insight into the mechanism underlying susceptibility to depression.

Mutations in the epidermal growth factor receptor (EGFR) are commonly occurring in glioblastoma. Enhanced activation of EGFR can occur through a variety of different mechanisms, both ligand-dependent and ligand-independent. Numerous evidence has suggested that EGFR is overexpressed in most of primary glioblastomas and some of the secondary glioblastomas and is characteristic of more aggressive glioblastoma phenotypes. Additionally, recent studies have revealed that wild-type EGFR, and to a greater extent hyper-activating EGFR mutants induced a substantial upregulation of Fyn expression. Furthermore, it was determined that Fyn expression is upregulated across a panel of patient-derived glioblastoma stem cells (GSCs) relative to normal progenitor controls. Moreover, researchers are continuously involved in elucidation of novel mechanism linking EGFR EGFR-expressing glioblastoma. The present review highlights current aspects of EGFR receptor in glioblastoma and concludes that the concept of EGFR signaling and related receptors and associated factors is evolving, however, it needs detailed evaluation for future clinical applications in cancer patients.

RNA modifications represent a novel layer of regulation of gene expression. Functional experiments revealed that N 6-methyladenosine (m 6 A) on messenger RNA (mRNA) plays critical roles in cell fate determination and development. m 6 A mark also resides in the decoding center of 18S ribosomal RNA (rRNA); however, the biological function of m 6 A on 18S rRNA is still poorly understood. Here, we report that methyltransferase-like 5 (METTL5) methylates 18S rRNA both in vivo and in vitro, which is consistent with previous reports. Deletion of Mettl5 causes a dramatic differentiation defect in mouse embryonic stem cells (mESCs). Mechanistically, the m 6 A deposited by METTL5 is involved in regulating the efficient translation of F-box and WD repeat domain-containing 7 (FBXW7), a key regulator of cell differentiation. Deficiency of METTL5 reduces FBXW7 levels and leads to the accumulation of its substrate c-MYC, thereby delaying the onset of mESC differentiation. Our study uncovers an important role of METTL5-mediated 18S m 6 A in mESC differentiation through translation regulation and provides new insight into the functional significance of rRNA m 6 A.

This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Key WordsLong non coding RNA • UCA1 • Cardiomyocyte apoptosis • p27 Abstract Background/Aims: Urothelial carcinoma-associated 1 (UCA1) is a recently identified long non coding RNA (lncRNA). However, few studies have explored its role in cardiomyocytes after focal cardiac ischemia reperfusion injury (CIR). Methods: Rat CIR models were established using ligation of the Lower Anterior Descending artery (LAD). Cell apoptosis and reactive oxygen species (ROS) production in cardiac tissues were explored using immunohistochemistry and DHE staining. lncRNA expression patterns were detected using microarray and validated by qPCR. Cell viability and apoptosis were examined using MTT assay and flow cytometry. Results: CIR significantly induced cell apoptosis and ROS production in the rat model. The results of microarray demonstrated the reduced expression of UCA1, which was validated by qPCR. Follow-up experiments showed that UCA1 was involved in H 2 O 2 -induced cell apoptosis. We further showed that UCA1 negatively correlated with the expression of p27. Moreover, overexpression of p27 could induce primary cardiomyocyte apoptosis. Conclusions: Reduction of UCA1 levels plays a pro-apoptotic role in primary cardiomyocytes partially through stimulation of p27 protein expression. These results are in agreement with the observed levels of UCA1, p27 and apoptosis after cardiac I/R injury, suggesting that UCA1 might have an important role during I/R injury.