Hepatocellular carcinoma is one of the most common and lethal cancers worldwide, especially in developing countries. In the present study, we found that the expression of a microRNA, miR-590-5P, was down-regulated and S100A10 was up-regulated in six hepatocellular carcinoma cell lines. The reporter gene assay showed that overexpression of miR-590-5P effectively reduced the activity of luciferase expressed by a vector bearing the 3′ untranslated region of S100A10 mRNA. Ectopic miR-590-5P overexpression mediated by lentiviral infection decreased expression of S100A10. Infection of Lv-miR-590-5P inhibited cell growth and induced cell cycle G1 arrest in HepG2 cells. In addition, miR-590-5P expression suppressed the expression of Wnt5a, cMyc and cyclin D1, and increased the phosphorylation of β-catenin and expression of Caspase 3, which may contribute to the inhibitory effect of miR-590-5P on cell growth. Taken together, our data suggest that down-regulation of miR-590-5P is involved in hepatocellular carcinoma and the restoration of miR-590-5P can impair the growth of cancer cells, suggesting that miR-590-5P may be a potential target molecule for the therapy of hepatocellular carcinoma.

Nucleic acids, including DNA, microRNA (miRNA), small interfering RNA (siRNA), and antisense oligonucleotide (ASO), are powerful gene regulators, which have been demonstrated as promising drug candidates for therapeutic treatments. Nevertheless, poor cellular membrane permeability and serum stability have greatly hindered the applications of nucleic acids in biomedicine. To address these issues, associate carriers that can encapsulate and protect nucleic acids are urgently required. Mesoporous silica nanoparticles (MSNs or MSNPs), which are nanomaterials with excellent biocompatibility, large surface area for functionalization, and tunable pore size for encapsulating different cargos, are emerging as novel and ideal biomaterials for different biomedical applications. In this review paper, we focus on the applications of MSNs in nucleic acid delivery and nucleic acid-guided therapeutic treatments. General strategies for the preparation of nucleic acid-MSN complexes will be firstly introduced, followed by a summary of recent applications of MSNs in nucleic acid delivery and nucleic acid-guided therapeutics.

MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression. Aberrant miRNA expression or function have close links with various human diseases. Therefore, therapeutic treatments with disease-associated miRNAs as targets are emerging. However, the intracellular miRNA networks are extremely complicated and poorly understood, which thus hinder the development of miRNA-targeted therapeutics. Small molecules that are able to regulate endogenous miRNAs hold great potential in both elucidation of miRNA networks and treatment of miRNA-related diseases. Herein, we summarize current strategies for discovery of small molecule modifiers of miRNAs, and we highlight aspects of miRNA cellular biology elucidated by using these small molecules and miRNAtargeted therapeutics realized by these small molecules. We envision that this area will expand dramatically in the near future and will ultimately contribute to a better understanding of miRNAinvolved cellular processes and development of therapeutic agents for miRNA-associated diseases.

In this study, we aimed to study the role of growth factor receptor-bound protein 2 (Grb2) in palmitic acid-induced steatosis and other "fatty liver" symptoms in vitro. HepG2 cells, with or without stably suppressed Grb2 expression, were incubated with palmitic acid for 24 h to induce typical clinical "fatty liver" features, including steatosis, impaired glucose metabolism, oxidative stress, and apoptosis. MTT and Oil Red O assays were applied to test cell viability and fat deposition, respectively. Glucose uptake assay was used to evaluate the glucose utilization of cells. Quantitative polymerase chain reaction and Western blot were used to measure expressional changes of key markers of insulin signaling, lipid/glucose metabolism, oxidative stress, and apoptosis. After 24-h palmitic acid induction, increased fat accumulation, reduced glucose uptake, impaired insulin signaling, enhanced oxidative stress, and increased apoptosis were observed in HepG2 cells. Suppression of Grb2 in HepG2 significantly reduced fat accumulation, improved glucose metabolism, ameliorated oxidative stress, and restored the activity of insulin receptor substrate-1/Akt and MEK/ERK pathways. In addition, Grb2 deficiency attenuated hepatic apoptosis shown by reduced activation of caspase-3 and fluorescent staining. Modulation of Bcl-2 and Bak1 also contributed to reduced apoptosis. In conclusion, suppression of Grb2 expression in HepG2 cells improved hepatic steatosis, glucose metabolism, oxidative stress, and apoptosis induced by palmitic acid incubation partly though modulating the insulin signaling pathway.

MicroRNAs (miRNAs) are small non-coding RNAs that have been identified as key endogenous biomolecules that are able to regulate gene expression at the post-transcriptional level. The abnormal expression or function of miRNAs has been demonstrated to be closely related to the occurrence or development of various human diseases, including cancers. Regulation of these abnormal miRNAs thus holds great promise for therapeutic treatments. In this review, we summarize exogenous molecules that are able to regulate endogenous miRNAs, including small molecule regulators of miRNAs and synthetic oligonucleotides. Strategies for screening small molecule regulators of miRNAs and recently reported small molecules are introduced and summarized. Synthetic oligonucleotides including antisense miRNA oligonucleotides and miRNA mimics, as well as delivery systems for these synthetic oligonucleotides to enter cells, that regulate endogenous miRNAs are also summarized. In addition, we discuss recent applications of these small molecules and synthetic oligonucleotides in therapeutic treatments. Overall, this review aims to provide a brief synopsis of recent achievements of using both small molecule regulators and synthetic oligonucleotides to regulate endogenous miRNAs and achieve therapeutic outcomes. We envision that these regulators of endogenous miRNAs will ultimately contribute to the development of new therapies in the future.