The role of tumor-derived exosomal LncRNA in tumor metastasis
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Emerging roles of exosomes in diagnosis, prognosis, and therapeutic potential in ovarian cancer: a comprehensive review
Ovarian cancer is a leading cause of cancer-related deaths in women, and the development of chemoresistance remains a major challenge during and after its treatment. Exosomes, small extracellular vesicles involved in intercellular communication, have emerged as potential biomarkers and therapeutic targets in ovarian cancer. This review summarizes the current literature on differences in exosomal protein/gene expression between chemosensitive and chemoresistant ovarian cancer, and the effects of exosomal modifications on chemotherapeutic response. Clinical studies have identified alterations in several exosomal components from ovarian cancer tissues and serum samples arising as a consequence of chemosensitivity, which indicates their potential usefulness as potential biomarkers for predicting the development of chemoresistance. Interventional investigations from in vitro and in vivo studies demonstrated that modulation of specific exosomal components can influence ovarian cancer cell phenotypes and individual responses to chemotherapy. Exosomal delivery of chemotherapeutic agents, such as cisplatin, has presented as a potential targeted drug delivery strategy for overcoming chemoresistance in preclinical models. In summary, this review highlights the potential for exosomal proteins and genes to be useful biomarkers for predicting chemotherapy response and being therapeutic targets for overcoming chemoresistance in ovarian cancer. However, future research is still needed to validate these findings and explore the clinical utility of exosomal biomarkers and therapeutics in ovarian cancer management. In addition, understanding the molecular mechanisms underlying exosome-mediated chemoresistance may provide valuable insights for the development of personalized therapeutic strategies, improving outcomes for patients with ovarian cancer.
3D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression
Colorectal carcinoma (CRC) is a deadly cancer with an aggressive nature, and how CRC tumor cells manage to translocate and proliferate in a new tissue environment remains not fully understood. Recently, higher-order chromatin structures and spatial genome organization are increasingly implicated in diseases including cancer, but in-depth studies of three-dimensional genome (3D genome) of metastatic cancer are currently lacking, preventing the understanding of the roles of genome organization during metastasis. Here we perform multi-omics profiling of matched normal colon, primary tumor, lymph node metastasis, liver metastasis and normal liver tissue from CRC patients using Hi-C, ATAC-seq and RNA-seq technologies. We find that widespread alteration of 3D chromatin structure is accompanied by dysregulation of genes including SPP1 during the tumorigenesis or metastasis of CRC. Remarkably, the hierarchy of topological associating domain (TAD) changes dynamically, which challenges the traditional view that the TAD structure between tumor and normal tissue is conservative. In addition, we define compartment stability score to measure large-scale alteration in metastatic tumors. To integrate multi-omics data and recognize candidate genes driving cancer metastasis, a pipeline is developed based on Hi-C, RNA-seq and ATAC-seq data. And three candidate genes ARL4C, FLNA, and RGCC are validated to be associated with CRC cell migration and invasion using in vitro knockout experiments. Overall, these data resources and results offer new insights into the involvement of 3D genome in cancer metastasis.
Emerging roles of extracellular vesicles in oral and maxillofacial areas
The oral and maxillofacial region is a highly complex area composed of multiple tissue types and bears various critical functions of the human body. Diseases in this region pose significant diagnostic and management challenges; therefore, exploring new strategies for early diagnosis, targeted treatment, and tissue reconstruction is key to improving patient prognosis and quality of life. Extracellular vesicles are a group of heterogeneous lipid-bilayer membrane structures secreted by most cell types, including exosomes, microvesicles, and apoptotic bodies. Present in various body fluids and tissues, they act as messengers via the transfer of nucleic acids, proteins, and metabolites to recipient cells. To date, studies have revealed the different roles of extracellular vesicles in physiological or pathological processes, as well as applications in disease diagnosis, prognosis, and treatment. The importance and tissue specificity of the dental and maxillofacial tissues indicate that extracellular vesicles derived from this region are promising for further research. This paper reviews the published data on extracellular vesicles derived from cells, body fluids, and tissues in oral and maxillofacial regions, summarizes the latest advances in extracellular vesicles from extensive sources, and concludes with a focus on the current research progress and application prospects of engineered exosomes in oral science.
Targeting of TAMs: can we be more clever than cancer cells?
With increasing incidence and geography, cancer is one of the leading causes of death, reduced quality of life and disability worldwide. Principal progress in the development of new anticancer therapies, in improving the efficiency of immunotherapeutic tools, and in the personification of conventional therapies needs to consider cancer-specific and patient-specific programming of innate immunity. Intratumoral TAMs and their precursors, resident macrophages and monocytes, are principal regulators of tumor progression and therapy resistance. Our review summarizes the accumulated evidence for the subpopulations of TAMs and their increasing number of biomarkers, indicating their predictive value for the clinical parameters of carcinogenesis and therapy resistance, with a focus on solid cancers of non-infectious etiology. We present the state-of-the-art knowledge about the tumor-supporting functions of TAMs at all stages of tumor progression and highlight biomarkers, recently identified by single-cell and spatial analytical methods, that discriminate between tumor-promoting and tumor-inhibiting TAMs, where both subtypes express a combination of prototype M1 and M2 genes. Our review focuses on novel mechanisms involved in the crosstalk among epigenetic, signaling, transcriptional and metabolic pathways in TAMs. Particular attention has been given to the recently identified link between cancer cell metabolism and the epigenetic programming of TAMs by histone lactylation, which can be responsible for the unlimited protumoral programming of TAMs. Finally, we explain how TAMs interfere with currently used anticancer therapeutics and summarize the most advanced data from clinical trials, which we divide into four categories: inhibition of TAM survival and differentiation, inhibition of monocyte/TAM recruitment into tumors, functional reprogramming of TAMs, and genetic enhancement of macrophages.
Strontium–Alix interaction enhances exosomal miRNA selectively loading in synovial MSCs for temporomandibular joint osteoarthritis treatment
The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) “difficult-to-treat”. Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix’s crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
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