The emerging role of non-coding RNAs in the regulation of PI3K/AKT pathway in the carcinogenesis process

The PI3K/AKT pathway is an intracellular signaling pathway with an indispensable impact on cell cycle control. This pathway is functionally related with cell proliferation, cell survival, metabolism, and quiescence. The crucial role of this pathway in the development of cancer has offered this pathway as a target of novel anti-cancer treatments. Recent researches have demonstrated the role of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in controlling the PI3K/AKT pathway. Some miRNAs such as miR-155-5p, miR-328-3p, miR-125b-5p, miR-126, miR-331-3p and miR-16 inactivate this pathway, while miR-182, miR-106a, miR-193, miR-214, miR-106b, miR-93, miR-21 and miR-103/107 enhance activity of this pathway. Expression levels of PI3K/AKT-associated miRNAs could be used to envisage the survival of cancer patients. Numerous lncRNAs such as GAS5, FER1L4, LINC00628, PICART1, LOC101928316, ADAMTS9-AS2, SLC25A5-AS1, MEG3, AB073614 and SNHG6 interplay with this pathway. Identification of the impact of miRNAs and lncRNAs in the control of the activity of PI3K/AKT pathway would enhance the efficacy of targeted therapies against this pathway. Moreover, each of the mentioned miRNAs and lncRNAs could be used as a putative therapeutic candidate for the interfering with the carcinogenesis. In the current study, we review the role of miRNAs and lncRNAs in controlling the PI3K/AKT pathway and their contribution to carcinogenesis. © 2021 The Author(s

miR-1: A comprehensive review of its role in normal development and diverse disorders

MicroRNA-1 (miR-1) is a conserved miRNA with high expression in the muscle tissues. In humans, two discrete genes, MIRN1-1 and MIRN1-2 residing on a genomic region on 18q11.2 produce a single mature miRNA which has 21 nucleotides. miR-1 has a regulatory role on a number of genes including heat shock protein 60 (HSP60), Kruppel-like factor 4 (KLF4) and Heart And Neural Crest Derivatives Expressed 2 (HAND2). miR-1 has critical roles in the physiological processes in the smooth and skeletal muscles as well as other tissues, thus being involved in the pathogenesis of a wide range of disorders. Moreover, dysregulation of miR-1 has been noted in diverse types of cancers including gastric, colorectal, breast, prostate and lung cancer. In the current review, we provide the summary of the data regarding the role of this miRNA in the normal development and the pathogenic processes. © 2020 The Author(s

The effect of galega officinalis on hormonal and metabolic profile in a rat model of polycystic ovary syndrome

Objectives: Polycystic ovary syndrome (PCOS) has been considered as one of the most common endocrine diseases among the females in their regenerative age with a prevalence range of 5 to 21. However, the purpose of the present study was to investigate the protective effect of Galega officinalis on metabolic as well as hormonal parameters in a rodent model of PCOS. Materials and Methods: Thirty-two Wistar female rats were used (n=8/group) in the study consisting of healthy control and experimental groups. The experimental groups were divided into 3 subgroups, including rats with PCOS which received no treatment (G1), PCOS group in which G. officinalis extract was administered daily at a dose of 200 mg/kg/orally (G2) for 2 weeks, and PCOS group in which G. officinalis extract was administered daily at a dose of 400 mg/kg/orally (G3) for 2 weeks. In all experimental groups, a single intramuscular injection of estradiol valerate led to inducing PCOS. After the end of treatment period, rats in all of the studied groups were anesthetized with ketamine/xylazine (5/1 mg/kg), then the blood samples obtained and their serum samples were applied for testing the fasting blood sugar (FBS), insulin, aromatase, and follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estrogen. The ovaries of rats were removed and fixed for histopathological examinations. Results: The serum levels of FBS, insulin, LH, FSH, and testosterone significantly increased in G1 in comparison to healthy rats (P < 0.05), while they were all significantly decreased in the treated groups received G. officinalis extract compared to rats affected by PCOS (P < 0.05). Moreover, the serum level of estrogen and the serum activity of aromatase were both significantly decreased in G1 in comparison to healthy rats (P < 0.05), while in treated groups, they were significantly increased compared to G1 which received no treatment (P < 0.05). Moreover, the number of follicles in ovaries affected by PCOS decreased, while both concentrations of G. officinalis extract could prevent this phenomenon. Conclusions: It seems that the extract of G. officinalis has a beneficial effect on the levels of the LH, FSH, testosterone, estradiol, aromatase, FBS, and insulin in alleviating the complications of PCOS. © 2018 The Author (s)

Non-coding RNAs modulate function of extracellular matrix proteins

The extracellular matrix (ECM) creates a multifaceted system for the interaction of diverse structural proteins, matricellular molecules, proteoglycans, hyaluronan, and various glycoproteins that collaborate and bind with each other to produce a bioactive polymer. Alterations in the composition and configuration of ECM elements influence the cellular phenotype, thus participating in the pathogenesis of several human disorders. Recent studies indicate the crucial roles of non-coding RNAs in the modulation of ECM. Several miRNAs such as miR-21, miR-26, miR-19, miR-140, miR-29, miR-30, miR-133 have been dysregulated in disorders that are associated with disruption or breakdown of the ECM. Moreover, expression of MALAT1, PVT1, SRA1, n379519, RMRP, PFL, TUG1, TM1P3, FAS-AS1, PART1, XIST, and expression of other lncRNAs is altered in disorders associated with the modification of ECM components. In the current review, we discuss the role of lncRNAs and miRNAs in the modification of ECM and their relevance with the pathophysiology of human disorders such as cardiac/ lung fibrosis, cardiomyopathy, heart failure, asthma, osteoarthritis, and cancers. © 2021 The Author(s

Hesperidin improves the follicular development in 3D culture of isolated preantral ovarian follicles of mice

In vitro follicular culture systems provide optimal culture models for research about the physiology of the ovary and support the clinical practices to achieve competent mature oocytes for in vitro fertilization. In vitro maturation of preantral follicles makes it possible to study the effects of therapeutic agents on various conditions or disorders of the ovary. Nowadays, preventive bioflavonoids against cancer, hypercholesterolemia, fatty liver, or a variety of toxic agents are in focus. The aim of this study was to design and investigate the impacts of different concentrations of hesperidin, a glycoside flavonoid, on the in vitro preantral follicle growth and maturation in the three-dimensional (3D) culture system which was made with sodium alginate. Preantral follicles (n = 1363) were mechanically isolated from immature mice ovaries, then, after capsulating, they were randomly divided into four groups: the control group received no concentration of hesperidin, and three experimental groups were supplemented with 10, 22.5, and 50 µmol/L of hesperidin. All groups were cultured for 12 days. At the end of the culture period, the percentage of survival rate, antrum formation, obtained metaphase II oocytes, and the secretion of 17β-estradiol and progesterone were significantly higher in the group Hesp 50 (50 µmol/L hesperidin). Moreover, the mean average of follicular diameter cultured in the group Hesp 50 was also increased and the mRNA expression levels of PCNA, FSH-R, and Bcl-2 genes were higher, while Bax mRNA expression was significantly reduced compared with the other groups. Follicles cultured in the presence of 50 µmol/L of hesperidin had a higher fertilization rate and embryo development. Adding hesperidin at the concentration of 50 µmol/L to the culture medium resulted in higher follicular growth and maturation and increased the rate of in vitro fertilization and embryo development. Impact statement: It has been stated that hesperidin has many pharmacological effects, such as anti-inflammatory and antioxidant effects, antimicrobial activity, and anti-carcinogenic activity; but hesperidin and its derivatives have been under investigation as anti-fertility factors for a very long time. However, our results show that hesperidin can improve mice follicular growth and maturation during in vitro 3D culture. Hesperidin as an antioxidant factor could enhance the mRNA expression levels of two important genes involved in folliculogenesis, PCNA, and FSH-R. Our results prove for the first time that hesperidin not only has deleterious effects on follicular development but can also increase rates of in vitro fertilization and embryo development. © 2019 by the Society for Experimental Biology and Medicine

The impact of the phytotherapeutic agent quercetin on expression of genes and activity of signaling pathways

Quercetin is a flavonoid existing in different herbs, fruits, seeds, nuts and tea. It has beneficial effects on human health through mediating antioxidant activities, immune-modulatory impacts and regulating metabolic pathways. These effects are most probably induced through modulation of activity of signaling pathways and expression of genes. Several in vitro studies have verified anti-proliferative effects of quercetin and its effect on expression of apoptotic genes and cell cycle-related genes. Moreover, through modulation of a number of proteins such as NF-kB, PARP, STAT3, Bax, Bcl-2, COX2, and cytokines, quercetin has beneficial effects in neurodegenerative disorders, liver diseases and diabetes. PI3K/AKT is the mostly linked pathway with beneficial effects of quercetin. In the current manuscript, we explain the impact of quercetin on expression of genes and function of cellular signaling cascades in different contexts. © 2021 The Author

Exploring the role of non-coding RNAs in autophagy

As a self-degradative mechanism, macroautophagy/autophagy has a role in the maintenance of energy homeostasis during critical periods in the development of cells. It also controls cellular damage through the eradication of damaged proteins and organelles. This process is accomplished by tens of ATG (autophagy-related) proteins. Recent studies have shown the involvement of non-coding RNAs in the regulation of autophagy. These transcripts mostly modulate the expression of ATG genes. Both long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been shown to modulate the autophagy mechanism. Levels of several lncRNAs and miRNAs are altered in this process. In the present review, we discuss the role of lncRNAs and miRNAs in the regulation of autophagy in diverse contexts such as cancer, deep vein thrombosis, spinal cord injury, diabetes and its complications, acute myocardial infarction, osteoarthritis, pre-eclampsia and epilepsy. Abbreviations: AMI: acute myocardial infarction; ATG: autophagy-related; lncRNA: long non-coding RNA; miRNA: microRNA. © 2021 Informa UK Limited, trading as Taylor & Francis Group

Contribution of miRNAs in the Pathogenesis of Breast Cancer

Breast cancer is the most frequently diagnosed cancer among females. Gene expression profiling methods have shown the deregulation of several genes in breast cancer samples and have confirmed the heterogeneous nature of breast cancer at the genomic level. microRNAs (miRNAs) are among the recently appreciated contributors in breast carcinogenic processes. These small-sized transcripts have been shown to partake in breast carcinogenesis through modulation of apoptosis, autophagy, and epithelial�mesenchymal transition. Moreover, they can confer resistance to chemotherapy. Based on the contribution of miRNAs in almost all fundamental aspects of breast carcinogenesis, therapeutic intervention with their expression might affect the course of this disorder. Moreover, the presence of miRNAs in the peripheral blood of patients potentiates these transcripts as tools for non-invasive diagnosis of breast cancer. © Copyright © 2021 Ghafouri-Fard, Khanbabapour Sasi, Abak, Shoorei, Khoshkar and Taheri

Interplay between PI3K/AKT pathway and heart disorders

The PI3K/AKT signaling has crucial role in the regulation of numerous physiological functions through activation of downstream effectors and modulation of cell cycle transition, growth and proliferation. This pathway participates in the pathogenesis of several human disorders such as heart diseases through regulation of size and survival of cardiomyocytes, angiogenic processes as well as inflammatory responses. Moreover, PI3K/AKT pathway participates in the process of myocardial injury induced by a number of substances such as H2O2, Mercury, lipopolysaccharides, adriamycin, doxorubicin and epirubicin. In this review, we describe the contribution of this pathway in the pathoetiology of myocardial ischemia/reperfusion injury and myocardial infarction, heart failure, cardiac hypertrophy, cardiomyopathy and toxins-induced cardiac injury. © 2022, The Author(s)