Advances in the regulation of adipogenesis and lipid metabolism by exosomal ncRNAs and their role in related metabolic diseases.

Exosomes are membrane-bound extracellular vesicles released following the fusion of multivesicular bodies (MVBs) with the cell membrane. Exosomes transport diverse molecules, including proteins, lipids, DNA and RNA, and regulate distant intercellular communication. Noncoding RNA (ncRNAs) carried by exosomes regulate cell-cell communication in tissues, including adipose tissue. This review summarizes the action mechanisms of ncRNAs carried by exosomes on adipocyte differentiation and modulation of adipogenesis by exosomal ncRNAs. This study aims to provide valuable insights for developing novel therapeutics.

Platelet-rich plasma promotes peripheral nerve regeneration after sciatic nerve injury.

The effect of platelet-rich plasma on nerve regeneration remains controversial. In this study, we established a rabbit model of sciatic nerve small-gap defects with preserved epineurium and then filled the gaps with platelet-rich plasma. Twenty-eight rabbits were divided into the following groups (7 rabbits/group): model, low-concentration PRP (2.5-3.5-fold concentration of whole blood platelets), medium-concentration PRP (4.5-6.5-fold concentration of whole blood platelets), and high-concentration PRP (7.5-8.5-fold concentration of whole blood platelets). Electrophysiological and histomorphometrical assessments and proteomics analysis were used to evaluate regeneration of the sciatic nerve. Our results showed that platelet-rich plasma containing 4.5-6.5- and 7.5-8.5-fold concentrations of whole blood platelets promoted repair of sciatic nerve injury. Proteomics analysis was performed to investigate the possible mechanism by which platelet-rich plasma promoted nerve regeneration. Proteomics analysis showed that after sciatic nerve injury, platelet-rich plasma increased the expression of integrin subunit ß-8 (ITGB8), which participates in angiogenesis, and differentially expressed proteins were mainly enriched in focal adhesion pathways. Additionally, two key proteins, ribosomal protein S27a (RSP27a) and ubiquilin 1 (UBQLN1), which were selected after protein-protein interaction analysis, are involved in the regulation of ubiquitin levels in vivo. These data suggest that platelet-rich plasma promotes peripheral nerve regeneration after sciatic nerve injury by affecting angiogenesis and intracellular ubiquitin levels.

lncRNA MELTF-AS1 facilitates osteosarcoma metastasis by modulating MMP14 expression.

Osteosarcoma is a highly aggressive cancer common in children and adolescents. There is still a lack of effective treatments for metastatic or recurrent osteosarcoma. The role of long non-coding RNAs (lncRNAs) in osteosarcoma has gradually attracted attention. Here, we identified lncRNAs that were abnormally expressed in metastatic osteosarcoma through analyzing the sequencing data of osteosarcoma tissues and selected upregulated lncRNA MELTF-AS1 for detailed study. The qRT-PCR analysis showed that the expression of MELTF-AS1 was increased in osteosarcoma tissues and cells, and the high expression of MELTF-AS1 indicated a poor prognosis of osteosarcoma patients. The high expression of MELTF-AS1 in osteosarcoma was partly due to the transcriptional activation of RREB1. The results of transwell assays, scratch wound healing assays, and the tail vein injection lung metastasis model demonstrated that knocking down MELTF-AS1 inhibited metastasis ability of osteosarcoma cells. Furthermore, the results of RNA pull-down assays, luciferase reporter assays, and RNA immunoprecipitation (RIP) assays revealed that MELTF-AS1 could regulate MMP14 expression through interaction with miR-485-5p. Our study suggested that MELTF-AS1 functioned as a pro-metastasis gene in osteosarcoma by upregulating MMP14 and that it could be a potential therapeutic and diagnostic target for osteosarcoma.

The Role of LINC00284 in the Development of Thyroid Cancer via Its Regulation of the MicroRNA-30d-5p-Mediated ADAM12/Notch Axis.

Thyroid cancer is a commonly diagnosed endocrine malignancy with increasing incidence worldwide. Long noncoding RNAs (lncRNAs) are known to function in the invasion and metastasis of thyroid cancer. According to the GSE66783 microarray dataset, long intergenic nonprotein coding RNA 284 (LINC00284) is aberrantly upregulated in thyroid cancer tissues. However, information regarding the specific role of LINC00284 in thyroid cancer remains elusive. Therefore, the current study set out to determine the role of LINC00284 in the development of thyroid cancer, along with an investigation of the underlying molecular mechanism. In parallel with the microarray data from GSE66783, LINC00284 was observed to be expressed at high levels in thyroid cancer cell lines. Moreover, loss-of-function experiments revealed that the downregulation of LINC00284 reduced aldehyde dehydrogenase (ALDH) activity and thyroid cancer cell proliferation, colony formation, and invasiveness, which promoted cell apoptosis. Mechanistically, using dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays, LINC00284 was identified to competitively bind to microRNA-30d-5p (miR-30d-5p), which was observed to be expressed at low levels in thyroid cancer tissues and cells and directly targets the oncogene a disintegrin and metalloproteinase 12 (ADAM12). Overexpression of miR-30d-5p exerted tumor-suppressive effects on the malignant activity of thyroid cancer cells, changes that were reversed by LINC00284 overexpression or ADAM12 overexpression. Furthermore, LINC00284 activated the Notch signaling pathway by competitively binding to miR-30d-5p and increasing the expression of ADAM12. Finally, by performing in vivo experiments, we found that LINC00284 silencing or miR-30d-5p overexpression suppressed the tumorigenic ability of thyroid cancer cells and that overexpression of miR-30d-5p inhibited the LINC00284-induced tumorigenesis of thyroid cancer cells. Collectively, our findings indicate that LINC00284 competitively binds to miR-30d-5p and activates the ADAM12-dependent Notch signaling pathway, thereby promoting the development of thyroid cancer.

Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network.

BACKGROUND: Accumulating amount of evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor pathogenesis. However, the roles of long non coding RNAs (lncRNAs) in the lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) still remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC. METHODS: The transcriptome sequencing data of lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from the SRA and TCGA databases. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct an lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the protein-protein interaction (PPI) network. The expression of the top 6 genes in the hub module was validated with mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The relationship between the hub gene-associated ceRNA network and the overall survival of patients with ICC was predicted by conducting a Kaplan-Meier survival analysis. RESULTS: Sixty co-expressed DEmRNAs were identified in the ceRNA network. The top 6 hub genes consisted of downregulated FOS, IGF2, FOXO1 and NTF3, upregulated IGF1R, and insignificantly downregulated HGF in ICC tissues, when compared to that of normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network consisting of 86 ceRNA modules. MME-AS1 and hsa-miR-182 were associated with overall survival in ICC patients. FOS, IGF1R, IGF2, FOXO1, and NTF3 might target "TGF-ß signaling pathway", "the hedgehog signaling pathway", "retinol metabolism", or "type II diabetes mellitus" pathways respectively. CONCLUSION: These results indicate that FOS, IGF1R, IGF2, FOXO1, and NTF3 were useful prognostic factors in determining the prognosis of patients with ICC.

Antigen-adjuvant effects of icariin in enhancing tumor-specific immunity in mastocytoma-bearing DBA/2J mice.

Cancer immunotherapy has attracted much attention in recent years because of the ability of immune system to identify tumor cells and limit their growth. Icariin (ICA) is a natural flavonoid glucoside isolated from Epimedium plants and has shown a variety of pharmacological activities such as anti-inflammatory effects, immunological regulation and anticancer potency. Furthermore, it has immunoadjuvant effects on enhancing Th1-immune response, suggesting that ICA may serve as an adjuvant for cancer immunotherapy. In this study, we used P815 mouse mastocytoma tumor model and immunized them with P815AB peptide and/or ICA. Our results demonstrated that ICA could increase the cytotoxic T lymphocytes (CTL) response for P815AB peptide on the tumor-bearing DBA/2J mice. In addition, the percentage of CD4+CD8+/CD3+CD69+/CD69+NKG2D+ positive cells in splenocytes of the tumor-bearing mice all significantly increased after combined immunization with ICA and P815AB peptide. This illustrated that ICA could enhance the immunogenicity of P815AB and improve the ability of T cells and CTLs in recognizing the tumor cells. Moreover, ICA improved the function of peritoneal macrophages with effects of inhibition on tumor growth. Besides, we discussed the possible mechanism of ICA to enhance body immunity by detecting the expression level of MHC-I and related genes in B16-F10 and RMA/S cells. The results suggested that ICA has the potential to up-regulate LMP/TAP related molecules and induce the expression of MHC-I, which increase the immune surveillance and keep cancer in remission. In conclusion, ICA showed an anti-tumor effect both in vitro and in vivo and may be an effective antigen adjuvant for cancer treatment by enhancing tumor-specific immunity.

4-Methylcatechol-induced cell damage in TM4 Sertoli cells.

4-Methylcatechol (4-MC) is one of the metabolites of quercetin, which is a potential drug for neuroprotection and tumorigenesis inhibition. This study was performed to investigate the cytotoxic effect of 4-MC in mouse TM4 Sertoli cells. TM4 Sertoli cell viability was significantly inhibited by 4-MC in a time- and dose-dependent manner. The number of apoptotic and dead cells was significantly increased after 4-MC treatment. Caspase 3 activity increased by prolonged exposure of TM4 Sertoli cells to 200 µM 4-MC. The 4-MC significantly upregulated the mRNA level of Bax gene and considerably downregulated the Bcl-2 gene expression in a concentration-dependent manner. Results showed that 4-MC could induce TM4 Sertoli cell apoptosis, and the cytotoxic effect of 4-MC on TM4 Sertoli cells may be associated with upregulated Bax gene expression, which induced caspase cascade activation.

In vivo near-infrared photothermal therapy and computed tomography imaging of cancer cells using novel tungsten-based theranostic probe.

Photothermal therapy, as a physical therapeutic technique to kill cancer, has generated a great deal of interest. Photothermal agents hence play a critical role in this modern therapy. We report the use of transition metal oxides as photothermal agents based on PEGylated WO3-x nanoparticles. The well-prepared nanoparticles presented effective results during photothermal therapy both in vitro and in vivo by using near-IR laser irradiation (980 nm, 0.5 W cm(-2)). The tumor cells were effectively damaged using low power density during a short irradiation time without destroying healthy tissues. In vitro results of photothermal therapy with PEGylated WO3-x nanoparticles proved to be effective on 4T1 murine breast cancer cells via a confocal microscopy method and MTT assay. In vivo results were further confirmed by hematoxylin and eosin (H & E) histological staining. Additionally, PEGylated WO3-x nanoparticles were shown to be effective as a CT imaging contrast agent on a tumor-bearing mouse model. Our results suggest that this generation of PEGylated WO3-x nanoparticles can potentially be used in oncological CT imaging and photothermal therapy.