Exosomal microRNAs (exo-miRs) contribute to cancer metastasis. To identify pro-metastatic circulating exo-miRs in hepatocellular carcinoma (HCC), next-generation sequencing-based plasma exo-miR profiles of 14 patients with HCC (eight non-metastatic and six with metastasis within 1 year of follow-up) were analyzed. Sixty-one miRs were significantly overexpressed among patients with metastatic HCC. Candidate miRs were selected through integrative analyses of two different public expression datasets, GSE67140 and The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA_LIHC). Integrative analyses revealed 3 of 61 miRs (miR-106b-5p, miR-1307-5p, and miR-340-5p) commonly overexpressed both in metastasis and vascular invasion groups, with prognostic implications. Validation was performed using stored blood samples of 150 patients with HCC. Validation analysis showed that circulating exo-miR-1307-5p was significantly overexpressed in the metastasis group (p = 0.04), as well as in the vascular invasion and tumor recurrence groups. Circulating exo-miR-1307-5p expression was significantly correlated with tumor stage progression (p < 0.0001). Downstream signaling pathways of miR-1307 were predicted using TargetScan and Ingenuity Pathway Analysis. On comprehensive bioinformatics analysis, the downstream pathway of miR-1307-5p, promoting epithelial–mesenchymal transition (EMT), showed SEC14L2 and ENG downregulation. Our results show that circulating exo-miR-1307-5p promotes metastasis and helps predict metastasis in HCC, and SEC14L2 and ENG are target tumor suppressor genes of miR-1307 that promote EMT.

This preliminary study aimed to screen non-coding RNAs (ncRNAs) from plasma exosomes as a new method for cervical cancer diagnosis. Differentially expressed RNAs were initially selected from among a group of 12 healthy individuals (normal group) and a pretreatment group of 30 patients with cervical cancer (cancer group). Then, we analyzed the association between an ncRNA-mRNA network and cancer using ingenuity pathway analysis after secondary selection according to the number and correlation of mRNAs (or ncRNAs) relative to changes in the expression of primarily selected ncRNAs (or mRNAs) before and after chemoradiotherapy. The number of RNAs selected from the initial RNAs was one from 13 miRNAs, four from 42 piRNAs, four from 28 lncRNAs, nine from 18 snoRNAs, 10 from 76 snRNAs, nine from 474 tRNAs, nine from 64 yRNAs, and five from 67 mRNAs. The combination of miRNA (miR-142-3p), mRNAs (CXCL5, KIF2A, RGS18, APL6IP5, and DAPP1), and snoRNAs (SNORD17, SCARNA12, SNORA6, SNORA12, SCRNA1, SNORD97, SNORD62, and SNORD38A) clearly distinguished the normal samples from the cancer group samples. We present a method for efficiently screening eight classes of RNAs isolated from exosomes for cervical cancer diagnosis using mRNAs (or ncRNAs) altered by chemoradiotherapy.

Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10⁻⁷ (odds ratio = 1.72) and 1.1 × 10⁻⁷ in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling.

Osteoporosis is a disease caused by impaired bone remodeling that is especially prevalent in elderly and postmenopausal women. Although numerous chemical agents have been developed to prevent osteoporosis, arguments remain regarding their side effects. Here, we demonstrated the effects of loganin, a single bioactive compound isolated from Cornus officinalis, on osteoblast and osteoclast differentiation in vitro and on ovariectomy (OVX)-induced osteoporosis in mice in vivo. Loganin treatment increased the differentiation of mouse preosteoblast cells into osteoblasts and suppressed osteoclast differentiation in primary monocytes by regulating the mRNA expression levels of differentiation markers. Similar results were obtained in an osteoblast–osteoclast co-culture system, which showed that loganin enhanced alkaline phosphatase (ALP) activity and reduced TRAP activity. In in vivo experiments, the oral administration of loganin prevented the OVX-induced loss of bone mineral density (BMD) and microstructure in mice and improved bone parameters. In addition, loganin significantly increased the serum OPG/RANKL ratio and promoted osteogenic activity during bone remodeling. Our findings suggest that loganin could be used as an alternative treatment to protect against osteoporosis.

Actin dynamics, mediated by various actin-binding proteins, plays an important role in adipocyte differentiation. We investigated the role of coactosin-like F-actin binding protein (Cotl1) in adipocyte differentiation in vitro and in vivo. Cotl1 expression level was increased during adipocyte differentiation in mouse 3T3-L1 cells and primary cultured adipose-derived stem cells (ADSCs) and during weight gain in adipose tissues. However, Cotl1 deficient in 3T3-L1 and ADSCs inhibited adipocyte differentiation, and Cotl1^−/− mice displayed resistance to high-fat diet (HFD)-induced weight gain, hepatic steatosis and adipocyte enlargement compared to HFD-fed wild type (WT) mice. Ingenuity Pathway Analysis of RNA-sequencing in adipose tissues of HFD-WT and HFD-Cotl1^−/− mice predicted complicated relationships between Cotl1, differentiation of adipocytes, obesity and organization of actin cytoskeleton. Particularly, peroxisome proliferator-activated receptor gamma (Pparg) emerged as a central player, with Cotl1 influencing Pparg expression, consequently regulating adipocyte differentiation. These findings suggest Cotl1 as a pivotal regulator of terminal adipocyte differentiation by modulating adipogenic genes.

The systemic gene interactions that occur during osteoporosis and their underlying mechanisms remain to be determined. To this end, mesenchymal stromal cells (MSCs) were analyzed from bone marrow samples collected from healthy individuals (n = 5) and patients with osteoporosis (n = 5). A total of 120 osteoporosis-related genes were identified using RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) software. In order to analyze these genes, we constructed a heatmap of one-way hierarchical clustering and grouped the gene expression patterns of the samples. The MSCs from one control participant showed a similar expression pattern to that observed in the MSCs of three patients with osteoporosis, suggesting that the differentiating genes might be important genetic determinants of osteoporosis. Then, we selected the top 38 genes based on fold change and expression, excluding osteoporosis-related genes from the control participant. We identified a network among the top 38 genes related to osteoblast and osteoclast differentiation, bone remodeling, osteoporosis, and sarcopenia using the Molecule Activity Predictor program. Among them, 25 genes were essential systemic genes involved in osteoporosis. Furthermore, we identified 24 genes also associated with diabetes and obesity, among which 10 genes were involved in a network related to bone and energy metabolism. The study findings may have implications for the treatment and prevention of osteoporosis.