Our previous study showed that wedelolactone, a compound isolated from Ecliptae herba, has the potential to enhance osteoblastogenesis. However, the molecular mechanisms by which wedelolactone promoted osteoblastogenesis from bone marrow mesenchymal stem cells (BMSCs) remain largely unknown. In this study, treatment with wedelolactone (2 μg/mL) for 3, 6, and 9 days resulted in an increase in phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal protein kinase (JNK), and p38. Phosphorylation of mitogen-activated protein kinases (MAPKs), ERK and JNK started to increase on day 3 of treatment, and p38 phosphorylation was increased by day 6 of treatment. Expression of bone morphogenetic protein (BMP2) mRNA and phosphorylation of Smad1/5/8 was enhanced after treatment of cells with wedelolactone for 6 and 9 days. The addition of the JNK inhibitor SP600125, ERK inhibitor PD98059, and p38 inhibitor SB203580 suppressed wedelolactone-induced alkaline-phosphatase activity, bone mineralization, and osteoblastogenesis-related marker genes including Runx2, Bglap, and Sp7. Increased expression of BMP2 mRNA and Smad1/5/8 phosphorylation was blocked by SP600125 and PD98059, but not by SB203580. These results suggested that wedelolactone enhanced osteoblastogenesis through induction of JNK- and ERK-mediated BMP2 expression and Smad1/5/8 phosphorylation.

Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors of the urinary system, accounting for around 2% of all cancer diagnoses and deaths worldwide. Clear cell RCC (ccRCC) is the most prevalent and aggressive histology with an unfavorable prognosis and inadequate treatment. Patients’ progression-free survival is considerably improved by surgery; however, 30% of patients develop metastases following surgery. Identifying novel targets and molecular markers for RCC prognostic detection is crucial for more accurate clinical diagnosis and therapy. Glycosylation is a critical post-translational modification (PMT) for cancer cell growth, migration, and invasion, involving the transfer of glycosyl moieties to specific amino acid residues in proteins to form glycosidic bonds through the activity of glycosyltransferases. Most cancers, including RCC, undergo glycosylation changes such as branching, sialylation, and fucosylation. In this review, we discuss the latest findings on the significance of aberrant glycans in the initiation, development, and progression of RCC. The potential biomarkers of altered glycans for the diagnosis and their implications in RCC have been further highlighted.

ST3Gal IV is one of the principal sialyltransferases responsible for the biosynthesis of α2, 3-sialic acid to the termini N-glycans or O-glycans of glycoproteins and glycolipids. It has been reported that ST3Gal IV expression is associated with gastric carcinoma, pancreatic adenocarcinoma and breast cancer. While the expression and functions of ST3Gal IV in cervical cancer are still poorly understood. In this study, we found that ST3Gal IV was downregulated in human cervical cancer tissues compared to normal cervix tissues, and ST3Gal IV expression was negatively associated with the pathological grade of cervical cancer. ST3Gal IV upregulation inhibited the growth and proliferation of cervical cancer HeLa and SiHa cells in vitro and in vivo. Furthermore, ST3Gal IV overexpression enhanced the expression of several Notch pathway components such as Jagged1, Notch1, Hes1 and Hey1, while cell cycle protein expression like Cyclin D1, Cyclin E1, CDK2 and CDK4 were decreased. These results indicate that expression of ST3Gal IV is reduced in cervical cancer and plays a negative role in cell proliferation via Notch/p21/CDKs signaling pathway. Thus, sialyltransferase ST3Gal IV might be a target for the diagnosis and therapy of cervical cancer.

Autophagy is a treatment target for many disorders, including cancer, and its specific role is becoming increasingly well known. In tumors, researchers pay attention to microribonucleic acids (miRNAs) with regulatory effects to develop more effective therapeutic drugs for autophagy and find new therapeutic targets. Various studies have shown that autophagy-related miRNAs play an irreplaceable role in different tumors, such as miR-495, miR-30, and miR-101. These miRNAs are associated with autophagy resistance in gastric cancer, non-small cell lung cancer, and cervical cancer. In recent years, autophagy-related miRNAs have also been reported to play a role in autophagy in urinary system tumors. This article reviews the regulatory effects of autophagy-related miRNAs in kidney, bladder, and prostate cancer and provides new ideas for targeted therapy of the three major tumors of the urinary system.

Background. The most common site of prostate cancer metastasis is bone tissue with many recent studies having conducted genomic and clinical research regarding bone metastatic prostate cancer. However, further work is needed to better define those patients that are at an elevated risk of such metastasis. Methods. SEER and TCGA databases were searched to develop a nomogram for predicting prostate cancer bone metastasis. Results. Herein, we leveraged the Surveillance, Epidemiology, and End Results (SEER) database to construct a predictive nomogram capable of readily and accurately predicted the odds of bone metastasis in prostate cancer patients. This nomogram was utilized to assign patients with prostate cancer included in The Cancer Genome Atlas (TCGA) to cohorts at a high or low risk of bone metastasis (HRBM and LRBM, respectively). Comparisons of these LRBM and HRBM cohorts revealed marked differences in mutational landscapes between these patient cohorts, with increased frequencies of gene fusions, somatic copy number variations (CNVs), and single nucleotide variations (SNVs), particularly in the P53 gene, being evident in the HRBM cohort. We additionally identified lncRNAs, miRNAs, and mRNAs that were differentially expressed between these two patient cohorts and used them to construct a competing endogenous RNA (ceRNA) network. Moreover, three weighted gene co-expression network analysis (WGCNA) modules were constructed from the results of these analyses, with KIF14, MYH7, and COL10A1 being identified as hub genes within these modules. We further found immune response activity levels in the HRBM cohort to be elevated relative to that in the LRBM cohort, with single sample gene enrichment analysis (ssGSEA) scores for the immune checkpoint signature being increased in HRBM patient samples relative to those from LRBM patients. Conclusion. We successfully developed a nomogram capable of readily detecting patients with prostate cancer at an elevated risk of bone metastasis.