Lung cancer therapeutic resistance, especially chemoresistance, is a key issue in the management of this malignancy. Despite the development of novel molecularly targeted drugs to promote therapeutic efficacy, 5‐year survival of lung cancer patients is still dismal. Molecular studies through the recent years have fortunately presented multiple genes and signaling pathways, which contribute to lung cancer chemoresistance, providing a better perception of the biology of tumor cells, as well as the molecular mechanisms involved in their resistance to chemotherapeutic agents. Among those mechanisms, transfer of extracellular vesicles, such as exosomes, between cancer cells and the surrounding noncancerous ones is considered as an emerging route. Exosomes can desirably function as signaling vesicles to transmit multiple molecules from normal cells to cancer cells and their microenvironment, or vice versa. Using this ability, exosomes may affect the cancer cells' chemoresistance/chemosensitivity. Recently, noncoding RNAs (esp. microRNAs and long noncoding RNAs), as key molecules transferred by exosomes, have been reported to play a substantial role in the process of drug resistance, through modulation of various proteins and their corresponding genes. Accordingly, the current review principally aims to highlight exosomal micro‐ and long noncoding RNAs involved in lung cancer chemoresistance. Moreover, major molecular mechanisms, which connect corresponding RNA molecules to drug resistance, will briefly be addressed, for better clarifying of possible roles of exosomal noncoding RNAs in promoting the effectiveness of lung cancer therapy.
Non-coding RNAs (ncRNAs) are functional RNA molecules that comprise about 80% of both mammals and prokaryotes genomes. Recent studies have identified a large number of small regulatory RNAs in Escherichia coli and other bacteria. In prokaryotes, RNA regulators are a diverse group of molecules that modulate a wide range of physiological responses through a variety of mechanisms. Similar to eukaryotes, bacterial microRNAs are an important class of ncRNAs that play an important role in the development and secretion of proteins and in the regulation of gene expression. Similarly, riboswitches are cis-regulatory structured RNA elements capable of directly controlling the expression of downstream genes in response to small molecule ligands. As a result, riboswitches detect and respond to the availability of various metabolic changes within cells. The most extensive and most widely studied set of small RNA regulators act through base pairing with RNAs. These types of RNAs are vital for prokaryotic life, activating or suppressing important physiological processes by modifying transcription or translation. The majority of these small RNAs control responses to changes in environmental conditions. Finally, clustered regularly interspaced short palindromic repeat (CRISPR) RNAs, a newly discovered RNA regulator group, contains short regions of homology to bacteriophage and plasmid sequences that bacteria use to splice phage DNA as a defense mechanism. The detailed mechanism is still unknown but devoted to target homologous foreign DNAs. Here, we review the known mechanisms and roles of non-coding regulatory RNAs, with particular attention to riboswitches and their functions, briefly introducing translational applications of CRISPR RNAs in mammals.
: Cancer is an important health issue worldwide. Cancer therapy is multifaceted, and drug resistance is still the major limiting factor in treatment of patients with this disease. Although the mechanisms of anticancer drug resistance have been broadly investigated, a massive biological signal pathway of Non-coding RNAs (ncRNAs) involved in this process has not been completely understood. Long noncoding RNAs (lncRNAs) are a kind of transcripts with a minimum length of 200 nucleotides in size which have a limited potential for coding proteins. The roles of these RNA molecules have been evaluated in relation to several pathological processes including tumor formation and progression. Increasing evidence haverecently reported that non-coding RNAs (ncRNAs), particularly long non-coding RNAs have significant roles in many cellular and genomic processes, and because of their potential in regulation specific genes, they are also involved in drug resistance. In this review, we review the literature on the features oflncRNA, their regulation roles in the gene expression related to chemoresistance and the potential of these RNAs as targeted therapies for personalized treatment in cancers.
Gliomas make up virtually 80% of all lethal primary brain tumors and are categorized based on their cell of origin. Glioblastoma is an astrocytic tumor that has an inferior prognosis despite the ongoing advances in treatment modalities. One of the main reasons for this shortcoming is the presence of the blood-brain barrier and blood-brain tumor barrier. Novel invasive and non-invasive drug delivery strategies for glioblastoma have been developed to overcome both the intact blood-brain barrier and leverage the disrupted nature of the blood-brain tumor barrier to target cancer cells after resection—the first treatment stage of glioblastoma. Exosomes are among non-invasive drug delivery methods and have emerged as a natural drug delivery vehicle with high biological barrier penetrability. There are various exosome isolation methods from different origins, and the intended use of the exosomes and starting materials defines the choice of isolation technique. In the present review, we have given an overview of the structure of the blood-brain barrier and its disruption in glioblastoma. This review provided a comprehensive insight into novel passive and active drug delivery techniques to overcome the blood-brain barrier, emphasizing exosomes as an excellent emerging drug, gene, and effective molecule delivery vehicle used in glioblastoma therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s12035-023-03365-0.
In vitro maturation (IVM) is considered a potential assisted reproductive technology that is a safer and simpler alternative to conventional in vitro fertilization. It is primarily used in patients with impaired oocyte maturation and for the treatment of infertile women who are at risk of fertility loss. In addition, IVM is currently used mainly in polycystic ovarian syndrome patients with a high ovarian response and is still considered an experimental option in fertility preservation. Producing highly competent oocytes during IVM is considered a key step in the success of in vitro production (IVP) of embryos. Some factors, such as culture medium conditions and other supplements, have a significant impact on oocyte IVM performance. One of the known disruptors of oocyte developmental competence in IVP is oxidative stress (OS), which is caused by an imbalance between the production and neutralization of reactive oxygen species (ROS). In vitro conditions induce supraphysiological ROS levels due to exposure to an oxidative environment and the isolation of the oocyte from the follicle protective antioxidant milieu. Given the importance of OS in oocyte competence, the establishment of standardized antioxidant IVM systems is critical for improving the overall success of IVP. This review focuses on the main antioxidants tested to protect oocytes against OS in IVM.
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