No abstract

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.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer‑related mortality worldwide. An increasing number of studies have demonstrated that microRNAs may be used as diagnostic, therapeutic and prognostic targets for human cancers, including HCC. The present study aimed to evaluate microRNA (miR)‑302a expression and function in HCC, and its underlying mechanisms. The results revealed that miR‑302a was expressed at low levels in HCC tissues and cell lines. Reduced miR‑302a expression was correlated with tumor‑node‑metastasis stage and lymph node metastasis in patients with HCC. Additionally, overexpression of miR‑302a reduced cell proliferation and invasion, and induced apoptosis in HCC cells. Vascular endothelial growth factor A (VEGFA) was demonstrated to be a direct target gene of miR‑302a. VEGFA was highly expressed in HCC tissues and inversely correlated with miR‑302a expression. Knockdown of VEGFA expression led to reduced HCC cell proliferation and invasion, and increased apoptosis rates, similar to miR‑302a overexpression, which suggested that VEGFA may be a functional downstream target of miR‑302a in HCC. These data suggested that this newly identified miR‑302a/VEGFA axis may be involved in HCC formation and progression. The present results also provide novel potential targets for the treatments of patients with HCC.

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.