Background: NPM1 promotes whereas ATF5 inhibits HCC proliferation; NPM1 and ATF5 are regulated in an opposite manner in normal hepatocytes and HCC. Results: NPM1 competes against HSP70 for ATF5 binding and promotes proteasome-and caspase-dependent ATF5 protein degradation. Conclusion: NPM1 is a novel ATF5-interacting protein and abrogates ATF5 function in HCC. Significance: We reveal a mechanism by which NPM1 promotes HCC proliferation and survival via regulation of ATF5.

Atherosclerosis is one of the major macrovascular complications of diabetes mellitus (DM), and it is the main cause of death from clinical observation. Among various cell types involved in this disorder, endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages play a crucial role in the occurrence and development of this disease. The regulation and stabilization of these cells are a key therapeutic strategy for DM-associated atherosclerosis. An increasing number of evidences implicate that various types of noncoding RNAs (ncRNAs) play a vital role in many cellular responses as well as in physiological and pathological processes of atherosclerosis and DM that drive atherogenic/antiatherogenic processes in those cells. Encouragingly, many ncRNAs have already been tested in animal experiments or clinical trials showing good performance. In this review, we summarize recent progresses in research on functional regulatory role of ncRNAs in atherosclerosis with DM. More importantly, we illustrate new thoughts and findings relevant to ncRNAs as potential therapeutic targets or biomarkers for atherosclerosis with DM.

Objective: Abnormal proliferation or migration of vascular smooth muscle cells (VSMCs) can lead to vessel lesions, resulting in atherosclerosis and in stent-restenosis (IRS). The purpose of our study was to establish the role of miR-378a-5p and its targets in regulating VSMCs function and IRS. Methods: EdU assays and Cell Counting Kit-8 (CCK-8) assays were applied to evaluate VSMCs proliferation, wound healing assays and transwell assays were applied to assess cells migration. Furthermore, quantitative reverse transcription–polymerase chain reaction (qRT-PCR) was performed to investigate the expression level of miR-378a-5p IRS patients and healthy individuals. Target genes were predicted using Target Scan and miRanda software, and biological functions of candidate genes were explored through bioinformatics analysis. Moreover, RNA-binding protein immunoprecipitation (RIP) was carried out to analyze the miRNAs interactions with proteins. We also used Immunofluorescence (IF) and fluorescence microscopy to determine the binding properties, localization and expression of miR-378a-5p with downstream target CDK1. Results: The expression of miR-378a-5p was increased in the group with stent restenosis compared with healthy people, as well as in the group which VSMCs stimulated by platelet-derived growth factor-BB (PDGF-BB) compared with NCs. MiR-378a-5p over-expression had significantly promoted proliferative and migratory effects, while miR-378a-5p inhibitor suppressed VSMC proliferation and migration. CDK1 was proved to be the functional target of miR-378a-5p in VSMCs. Encouragingly, the expression of miR-378a-5p was increased in patients with stent restenosis compared with healthy people, as well as in PDGF-BB-stimulated VSMCs compared with control cells. Furthermore, co-transfection experiments demonstrated that miR-378a-5p over-expression promoted proliferation and migration of VSMCs specifically by reducing CDK1 gene expression levels. Conclusion: In this investigatory, we concluded that miR-378a-5p is a critical mediator in regulating VSMC proliferation and migration by targeting CDK1/p21 signaling pathway. Thereby, interventions aimed at miR-378a-5p may be of therapeutic application in the prevention and treatment of stent restenosis.

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Icariin is a flavonoid derived from Epimedium sagittatum , and has a wide range of biological and pharmacological effects; however, little is known regarding its effect on drug-resistant ovarian cancer and the signal transduction pathways underlying the regulation of apoptosis and autophagy. The present study aimed to investigate the re-sensitization effects of icariin exerted on an ovarian cancer cell line. Autophagy was analyzed in a SKVCR cell line that had been treated with icariin. We investigated the sensitivity of SKVCR cells to cisplatin, as well as the effects of an autophagy agonist (rapamycin) on autophagy, apoptosis, and the protein kinase B (AKT) signaling pathway. Finally, the mechanism underlying the effects of autophagy-related (ATG) protein ATG5 overexpression on autophagy, apoptosis and AKT signaling in SKVCR cells were determined. The results revealed that treatment with icariin inhibited cell viability and autophagy, but promoted G0/G1 phase cell cycle arrest and apoptosis as determined by Cell Counting Kit-8, immunofluorescence and flow cytometry assays, respectively. Icariin reduced the resistance of SKVCR cells to cisplatin in vitro by inducing G1/S cell cycle transition, apoptosis and inhibiting autophagy. Furthermore, enhanced autophagy induced by rapamycin treatment or overexpression of ATG5 partially reversed the effect of icariin on cisplatin resistance and autophagy in SKVCR cells. At the molecular level, rapamycin treatment or overexpression of ATG5 reversed the effects of icariin on the expression of autophagy-associated proteins, including microtubule-associated protein 1 light chain 3β, Beclin-1, ATG5 and p62, and the AKT/mammalian target of rapamycin (mTOR) pathway. Collectively, our results suggested that icariin enhances the chemosensitivity of SKVCR cells by suppressing autophagy via activation of the AKT/mTOR signaling pathway.