Prostate cancer commonly affects the urinary tract of men and metastatic prostate cancer has a very low survival rate. Apelin belongs to the family of adipokines and is associated with cancer development and metastasis. However, the effects of apelin in prostate cancer metastasis is undetermined. Analysis of the database revealed a positive correlation between apelin level with the progression and metastasis of prostate cancer patients. Apelin treatment facilitates cell migration and invasion through inhibiting tissue inhibitor of metalloproteinase 2 (TIMP2) expression. The increasing miR-106a-5p synthesis via c-Src/PI3K/Akt signaling pathway is controlled in apelin-regulated TIMP2 production and cell motility. Importantly, apelin blockade inhibits prostate cancer metastasis in the orthotopic mouse model. Thus, apelin is a promising therapeutic target for curing metastatic prostate cancer.

https://www.mdpi.com/2073-4409/11/20/3285/pdf?version=1666343031

Apelin Promotes Prostate Cancer Metastasis by Downregulating TIMP2 via Increases in miR-106a-5p Expression

Sarcomas, comprising approximately 1% of human malignancies, show a poor response to treatment and easy recurrence. Metabolic reprogramming play an important role in tumor development in sarcomas. Accumulating evidence shows that non-coding RNAs (ncRNAs) participate in regulating the cellular metabolism of sarcomas, which improves the understanding of the development of therapy-resistant tumors. This review addresses the regulatory roles of metabolism-related ncRNAs and their implications for sarcoma initiation and progression. Dysregulation of metabolism-related ncRNAs is common in sarcomas and is associated with poor survival. Emerging studies show that abnormal expression of metabolism-related ncRNAs affects cellular metabolism, including glucose, lipid, and mitochondrial metabolism, and leads to the development of aggressive sarcomas. This review summarizes recent advances in the roles of dysregulated metabolism-related ncRNAs in sarcoma development and stemness and describes their potential to serve as biological biomarkers for disease diagnosis and prognosis prediction, as well as therapeutic targets for treating refractory sarcomas. 

Non-coding RNAs in metabolic reprogramming of bone and soft tissue sarcoma: Fundamental mechanism and clinical implication.

Sex differences in vision and hearing impairments across age and European regions : Findings from SHARE.

Osteosarcoma (OS) is a primary malignant bone tumor that occurs in children and adolescents, and the PI3K/AKT pathway is overactivated in most OS patients. MicroRNAs (miRNAs) are highly conserved endogenous non-protein-coding RNAs that can regulate gene expression by repressing mRNA translation or degrading mRNA. MiRNAs are enriched in the PI3K/AKT pathway, and aberrant PI3K/AKT pathway activation is involved in the development of osteosarcoma. There is increasing evidence that miRNAs can regulate the biological functions of cells by regulating the PI3K/AKT pathway. MiRNA/PI3K/AKT axis can regulate the expression of osteosarcoma-related genes and then regulate cancer progression. MiRNA expression associated with PI3K/AKT pathway is also clearly associated with many clinical features. In addition, PI3K/AKT pathway-associated miRNAs are potential biomarkers for osteosarcoma diagnosis, treatment and prognostic assessment. This article reviews recent research advances on the role and clinical application of PI3K/AKT pathway and miRNA/PI3K/AKT axis in the development of osteosarcoma. Graphical Abstract Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma.

/pdf/functional-role-of-microrna-pi3k-akt-axis-in-osteosarcoma-2mc9o2zt.pdf

Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma

Sarcoma is a heterogeneous group of mesenchymal neoplasms with a high rate of lung metastasis. The cellular mechanisms responsible for sarcoma metastasis remain poorly understood. Furthermore, there are limited efficacious therapeutic strategies for treating metastatic sarcoma. Improved diagnostic and therapeutic modalities are of increasing importance for the treatment of sarcoma due to their high mortality in the advanced stages of the disease. Recent evidence demonstrates that the exosome, a type of extracellular vesicle released by virtually all cells in the body, is an important facilitator of intercellular communication between the cells and the surrounding environment. The exosome is gaining significant attention among the medical research community, but there is little knowledge about how the exosome affects sarcoma metastasis. In this review, we summarize the multifaceted roles of sarcoma-derived exosomes in promoting the process of metastasis via the formation of pre-metastatic niche (PMN), the regulation of immunity, angiogenesis, vascular permeability, and the migration of sarcoma cells. We also highlight the potential of exosomes as innovative diagnostic and prognostic biomarkers as well as therapeutic targets in sarcoma metastasis.

/pdf/the-roles-of-exosomes-in-metastasis-of-sarcoma-from-3mg2ufor.pdf

The Roles of Exosomes in Metastasis of Sarcoma: From Biomarkers to Therapeutic Targets

Osteosarcoma is the most common type of primary malignant bone cancer, and it is associated with high rates of pulmonary metastasis. Integrin αvβ3 is critical for osteosarcoma cell migratory and invasive abilities. Chemokine (C-C motif) ligand 4 (CCL4) has diverse effects on different cancer cells through its interaction with its specific receptor, C-C chemokine receptor type 5 (CCR5). Analysis of mRNA expression in human osteosarcoma tissue identified upregulated levels of CCL4, integrin αv and β3 expression. Similarly, an analysis of records from the Gene Expression Omnibus (GEO) dataset showed that CCL4 was upregulated in human osteosarcoma tissue. Importantly, the expression of both CCL4 and integrin αvβ3 correlated positively with osteosarcoma clinical stages and lung metastasis. Analysis of osteosarcoma cell lines identified that CCL4 promotes integrin αvβ3 expression and cell migration by activating the focal adhesion kinase (FAK), protein kinase B (AKT), and hypoxia inducible factor 1 subunit alpha (HIF-1α) signaling pathways, which can downregulate microRNA-3927-3p expression. Pharmacological inhibition of CCR5 by maraviroc (MVC) prevented increases in integrin αvβ3 expression and cell migration. This study is the first to implicate CCL4 as a potential target in the treatment of metastatic osteosarcoma.

Yan-You Lai

Papers

CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvβ3 Axis