Abstract. MicroRNA-34a (miR-34a) functions as a tumor suppressor gene and inhibits abnormal cell growth by regulating the expression of other genes. The role of miR-34a in regulating sirtuin 1 (SIRT1) in prostate cancer remains unclear. The objective of the present study was to investigate the biological function and molecular mechanisms of miR-34a regulation of SIRT1 in human prostate cancer samples and the human prostate cancer cell line, PC-3. Fresh prostate tissues were obtained from patients, and the miR-34a expression in prostate cancer tissues was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). qPCR and western blotting were performed to assess the effects of miR-34a overexpression on SIRT1 regulation in PC-3 cells, and the cell growth was assessed by Cell Counting Kit-8 (CCK-8). Flow cytometry was used to assess the cell cycle status of the cells. The miR-34a expression levels in prostate cancer tissues were significantly reduced compared with adjacent normal prostate tissues (P<0.05). SIRT1 expression levels in PC-3 cells with over-expression of miR-34a were significantly reduced compared with those in the negative control (P<0.05). The over-expression of miR-34a inhibited PC-3 cells growth and resulted in increased cell cycle arrest compared with the negative control (P<0.05). In conclusion, miR-34a inhibits the human prostate cancer cell proliferation, in part, through the downregulation of SIRT1 expression.

Edited by Didier StainierBeclin 1/Atg6 is an essential autophagy gene, and deficiency of this gene in organisms leads to impaired autophagic flux, usually with cell apoptosis; however, the causative mechanism of cell apoptosis is not clear. Here, we knocked out the beclin 1 gene in zebrafish and found that autophagic flux is disrupted in mutants. Beclin 1-deficient zebrafish live through embryogenesis but die at larval stage. We found accumulated protein aggregates and vigorous apoptosis in mutant larvae, predominantly in the liver. The hepatic cell apoptosis in mutants results from an endoplasmic reticulum (ER) stress response; however, it is not the leading cause of mutant larval lethality. Our work proposes that ER stress induces cell apoptosis in Beclin 1-deficient organisms.Autophagy is an ancient self-digestive mechanism in eukaryotic cells, delivering cytoplasmic materials into the lysosome for degradation. The cargoes include damaged organelles, aberrant proteins, invading pathogens, and other cellular contents. The digestive products can be used for macromolecule synthesis and energy production. Therefore, autophagy plays important roles in the maintenance of cellular hemostasis, response to energy deprivation, and clearance of invading microorganism pathogen [1,2]. Among the three types of autophagy, namely microautophagy, chaperone-mediated autophagy, and macroautophagy, macroautophagy draws the most attention [3,4] and is hereafter called autophagy in this study. Autophagy is regulated by a group of genes, known as autophagy-related gene (Atg), with majority of them firstly identified by genetic screens in yeast and highly conserved among species [5]. Beclin 1/Atg6 is an essential for autophagy induction. It directly binds to Vps34 (Pik3c3) through its evolutionarily conserved domain (ECD) forming the class III phosphatidylinositol 3-kinase (PI3KIII) complex to produce phosphatidylinositol 3-phosphate (PtdIns(3)P), an essential lipid-based compound for initial steps of autophagosome formation [6].To study the biological functions of Beclin 1/Atg6, the loss-of-function mutants were generated in many Abbreviations Atg, autophagy-related gene; BH3, Bcl-2 homology-3 domain; CCD, coiled-coil domain; ECD, evolutionarily conserved domain; ER, endoplasmic reticulum; PC, Purkinje cell; PI3KIII, class III phosphatidylinositol 3-kinase; PtdIns(3)P, phosphatidylinositol 3-phosphate; TUDCA, tauroursodeoxycholic acid; VE, visceral endoderm; WISH, Whole-mount in situ hybridization.