Background: Identification of targetable biomarkers to improve early disease detection and overall patient outcomes is becoming an urgent need in clinical oncology. Ovarian cancer (OC) has one of the highest mortality rates among gynecological cancers. It is asymptomatic and almost always diagnosed at an advanced stage (III or IV), leading to a 5-year survival rate of approximately 35%. Methods: Current therapeutic approaches for OC are very limited and mainly consist of cytoreductive surgery and cisplatin plus taxane-based chemotherapy. No gender and tumor specific biomarkers are known. Exosomes, lipid bilayer vesicles of endocytic origin secreted by most cell types, represent sources of information for their involvement in the onset and progression of many diseases. Hence, research on exosome contents as tools and targets in precise oncology therapy provides knowledge essential to improving diagnosis and prognosis of the disease. Results: This review attempts to give an overview of how exosomes are implicated in ovarian carcinoma pathogenesis to trigger further cancer exosome-based investigations aimed at developing ovarian cancer fine-tuning diagnostic methodologies. Conclusions: It is essential to investigate exosome-based cancer drugs to advance understanding, improve treatment plans, create personalized strategies, ensure safety, and speed up clinical translation to increase patients' overall survival and quality of life. Papers published in PubMed and Web of Science databases in the last five years (2020-2024) were used as a bibliographic source.

Cancer remains a major global health challenge, with prostate cancer, lung cancer, colorectal cancer, and breast cancer accounting for nearly half of all diagnoses. Despite advancements in cancer treatment, metastasis to distant organs continues to be the leading cause of cancer-related mortality. The progression of cancer involves the alteration of numerous genes, with dynamic changes in chromatin organization and histone modifications playing a critical role in regulating cancer-associated genes. Special AT-rich sequence-binding protein 1 (SATB1), a critical chromatin organizer, plays a pivotal role in cancer progression by regulating gene expression, chromatin remodeling, and cell signaling pathways. SATB1 binds to AT-rich DNA sequences, acting as a scaffold for chromatin-modifying enzymes and transcription factors, thus coordinating the regulation of extensive gene networks. Its overexpression has been implicated in a wide range of cancers and is associated with poor prognosis, aggressive tumor phenotypes, and enhanced epithelial-mesenchymal transition (EMT). Moreover, SATB1's activity is modulated by microRNAs (miRNAs) and post-translational modifications, further contributing to its complex regulatory functions. Given its crucial involvement in cancer progression and metastasis, SATB1 has emerged as a promising target for novel therapeutic strategies. This review delves into the molecular mechanisms of SATB1 in cancer and explores potential therapeutic approaches for targeting this key regulator in cancer treatment.

Bladder carcinoma (BC) is the tenth most frequent malignancy worldwide, with high morbidity and mortality rates. Despite recent treatment advances, high-grade BC and muscle-invasive BC present with significant progression and recurrence rates, urging the need for alternative treatments. The microRNA-21 (miR-21) has superexpression in many malignancies and is associated with cellular invasion and progression. One of its mechanisms of action is the regulation of RECK, a tumor suppressor gene responsible for inhibiting metalloproteinases, including MMP9. In a high-grade urothelial cancer cell line, we aimed to assess if miR-21 downregulation would promote RECK expression and decrease MMP9 expression. We also evaluated cellular migration and proliferation potential by inhibition of this pathway. In a T24 cell line, we inhibited miR-21 expression by transfection of a specific microRNA inhibitor (anti-miR-21). There were also control and scramble groups, the last with a negative microRNA transfected. After the procedure, we performed a genetic expression analysis of miR-21, RECK, and MMP9 through qPCR. Migration, proliferation, and protein expression were evaluated via wound healing assay, colony formation assay, flow cytometry, and immunofluorescence.After anti-miR-21 transfection, miR-21 expression decreased with RECK upregulation and MMP9 downregulation. The immunofluorescence assay showed a significant increase in RECK protein expression (p < 0.0001) and a decrease in MMP9 protein expression (p = 0.0101). The anti-miR-21 transfection significantly reduced cellular migration in the wound healing assay (p < 0.0001). Furthermore, in the colony formation assay, the anti-miR-21 group demonstrated reduced cellular proliferation (p = 0.0008), also revealed in the cell cycle analysis by flow cytometry (p = 0.0038). Our results corroborate the hypothesis that miR-21 is associated with BC cellular migration and proliferation, revealing its potential as a new effective treatment for this pathology.

As an aggressive malignancy, glioblastoma multiforme (GBM) is the most common type of brain tumor. The existing treatments have shown limited achievement in increasing the overall survival of patients. Therefore, identifying the key molecules involved in GBM will provide new potential therapeutic targets. Carmustine is an alkylating agent used as a supplementary therapeutic option for GBM. However, the extensive use of carmustine has been limited by uncertainty about its efficacy. MicroRNAs (miRNAs) are essential in post-transcriptional gene regulation. Many aberrantly expressed miRNAs have been detected in various types of human cancer, including GBM. In this study, we evaluated the potential therapeutic effect of miR-143 in combination with carmustine on GBM cells. A172 cells were transfected with miR-143 mimics and then treated with carmustine. To assess the cell viability, apoptosis induction, and cell cycle progression, the MTT assay, Annexin V/PI apoptosis assay, and flow cytometry were used, respectively. Furthermore, qRT-PCR assay was applied to evaluate the expression level of genes related to apoptosis. The obtained results evidenced that miR-143 transfection could promote the sensitivity of A172 cells to carmustine and enhance carmustine-induced apoptosis via modulating the expression levels of Caspase-3, Caspase-9, Bax, and Bcl-2. Also, our results revealed that combination therapy could effectively diminish cell cycle progression in A172 cells. In conclusion, these results confirmed that miR-143 could enhance carmustine-mediated suppression of cell proliferation and improve the chemosensitivity of A172 cells to this chemotherapeutic agent. Therefore, miR-143 combination therapy may be a promising GBM treatment approach.

Despite significant advances in treatments, ovarian cancer (OC) remains one of the most prevalent and lethal gynecological cancers in women. The frequent detection at the advanced stages has contributed to low survival rates, resistance to various treatments, and disease recurrence. Thus, a more effective approach is warranted to combat OC. The cytokine Interleukin-6 (IL6) has been implicated in various stages of OC development. High IL6 levels are also correlated with a lower survival rate in OC patients. In this current review, we summarized the pivotal roles of IL6 in OC, including the initiation, development, invasion, metastasis, and drug resistance mechanisms. This article systematically highlights how targeting IL6 improves OC outcomes by altering various cancer processes and reports the ongoing clinical trials that would further shape the IL6-based targeted therapies. This review also suggests how combining IL6-targeted therapies with other therapeutic strategies could further enhance their efficacy to combat OC.

Ovarian cancer is one of the leading causes of mortality among women worldwide. However, early detection can significantly reduce mortality rates and mitigate subsequent complications related to both economic burden and mental well-being. Despite the development in the field of medical diagnosis, the death rates due to ovarian cancer have sharply increased. Among the recent technologies suggested as suitable diagnostic techniques for the early detection of ovarian cancer, biosensor technology has emerged as a cutting-edge technology, with electrochemical biosensors providing one of the most efficient types of biosensors. Therefore, this review discusses the application of electrochemical biosensors as a viable alternative to conventional diagnostic techniques for the timely identification of ovarian cancer, its advantages over other types of biosensors and conventional diagnostic techniques, and the types of electrochemical biosensors.

Hepatocellular carcinoma (HCC) is the third prime cause of malignancy-related mortality worldwide. Early and accurate identification of HCC is crucial for good prognosis, efficacy of therapy, and survival rates of the patients. We aimed to develop a machine-learning model incorporating differentially expressed RNA signatures with laboratory parameters to construct an RNA signature-based diagnostic model for HCC.

We have used five classifiers (KNN, RF, SVM, LGBM, and DNNs) to predict the liver disease (HCC). The classifiers were trained on 187 samples and then tested on 80 samples. The model included 22 features (age, sex, smoking, cirrhosis, non-cirrhosis, albumin, ALT, AST bilirubin (total and direct), INR, AFP, HBV Ag, HCV Abs, RQmiR-1298, RQmiR-1262, RQmiR-106b-3p, RQmRNARAB11A, and RQSTAT1, RQmRNAATG12, RQLnc-WRAP53, RQLncRNA- RP11-513I15.6).

LGBM achieved the highest accuracy of 98.75% in predicting HCC among all models surpassing Random Forest (96.25%), DNN (91.25%), SVC (88.75%), and KNN (87.50%).

Our machine-learning model incorporating the expression data of RAB11A/STAT1/ATG12/miR-1262/miR-1298/miR-106b-3p/lncRNA-RP11-513I15.6/lncRNA-WRAP53 signature and clinical data represents a potential novel diagnostic model for HCC.

Gynecological cancer is a term referring to malignancies that typically involve ovarian, cervical, uterine, vaginal, and vulvar cancer. Combined, these cancers represent major causes of morbidity and mortality in women with a heavy socioeconomic impact. MiRNAs are small non-coding RNAs that are intensively studied in the field of cancer and changes in them have been linked to a variety of processes involved in cancer that range from tumorigenesis to prognosis and metastatic potential. This review aims to summarize the existing literature that has linked miRNAs with each of the female malignancies as potential biomarkers in diagnosis (circulating miRNAs), in tumor histology and prognosis (as tissue biomarkers), and for local (lymph node) and distant metastatic disease.

Pituitary adenomas (PAs) are an array of tumors originating from the pituitary gland. PAs are sorted as functional or nonfunctional according to their hormonal activity and classified according to size into microadenomas and macroadenomas. Still, the cellular events that trigger the transformations in pituitary neoplasms are not fully understood, and the current classification methods do not precisely predict clinical behavior. A rising number of researches have emphasized the role of miRNAs, that drawn more attention as oncogenic molecules or tumor suppressors. The etiopathological mechanisms of PAs include multiple molecular cascades that are influenced by different miRNAs. miRNAs control the cell cycle control, pro- or antiapoptotic processes, and tumor invasion and metastasis. miRNAs offer a novel perspective on tumor features and behaviors and might be valuable in prognostication and therapeutic plans. In pituitary adenomas, miRNAs showed a specific expression pattern depending on their size, cell origin, remission, and treatments. Screening miRNA expression patterns is promising to monitor and evaluate recurrence, as well as to investigate the efficacy of radiation and chemotherapy for PAs exhibiting aggressive behavior. Thus, the current review investigated the interplay of the miRNAs' pivotal role in offering new opportunities to translate these innovative epigenetic tools into healthcare applications.

Cerebral vasospasm (CVS) is an important contributor to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), leading to high morbidity and long-term disability. While several microRNAs (miRNAs) have been implicated in vasospasm, the underlying mechanisms for CVS remain poorly understood. Our study aims to identify miRNAs that may contribute to the development of CVS. Whole-blood samples were obtained during or outside of vasospasm from aSAH patients whose maximal vasospasm was moderate or severe. MiRNAs were isolated from serial whole-blood samples, and miRNA sequencing was performed. Differentially expressed miRNAs were identified and the expression levels in patients' samples were verified using real-time qPCR. The biological functions of identified miRNA were evaluated in human brain endothelial cells (HBECs). MiRNA profiling revealed significant upregulation of miR-148b-3p in patients during CVS. We demonstrated that miR-148b-3p directly targeted and decreased the expression of ROCK1, affecting cell proliferation, migration, and invasion of HBECs through the ROCK-LIMK-Cofilin pathway. We propose that the upregulation of miRNA-148b-3p plays a role in the development of CVS by regulating actin cytoskeletal dynamics in HBECs, which is crucial for vascular function. Our study highlights miR-148b-3p as a potential diagnostic marker as well as therapeutic target for CVS following aSAH.

Sex characteristics exhibit significant disparities in various human diseases, including prevalent cardiovascular diseases, cancers, metabolic disorders, autoimmune diseases, and neurodegenerative diseases. Risk profiles and pathological manifestations of these diseases exhibit notable variations between sexes. The underlying reasons for these sex disparities encompass multifactorial elements, such as physiology, genetics, and environment. Recent studies have shown that human body systems demonstrate sex-specific gene expression during critical developmental stages and gene editing processes. These genes, differentially expressed based on different sex, may be regulated by androgen or estrogen-responsive elements, thereby influencing the incidence and presentation of cardiovascular, oncological, metabolic, immune, and neurological diseases across sexes. However, despite the existence of sex differences in patients with human diseases, treatment guidelines predominantly rely on male data due to the underrepresentation of women in clinical trials. At present, there exists a substantial knowledge gap concerning sex-specific mechanisms and clinical treatments for diverse diseases. Therefore, this review aims to elucidate the advances of sex differences on human diseases by examining epidemiological factors, pathogenesis, and innovative progress of clinical treatments in accordance with the distinctive risk characteristics of each disease and provide a new theoretical and practical basis for further optimizing individualized treatment and improving patient prognosis.

This study aimed to investigate the association of rs12976445 polymorphism in the promoter region of miR-125a and rs2114358 in the precursor region of miR-1206 to breast cancer susceptibility.

A total of 230 participants (110 breast cancer and 120 controls) enrolled in this study and extracted genomic DNA. The genotypes were determined by the Tetra-ARMS method. The allele and genotype frequencies were determined.

Allele variation in the rs12976445 (miR-125a) sequence increased the risk of breast cancer; a significant relationship was observed between breast cancer and allele change in individuals with the C allele (p = 0.01). However, allele variation in the rs2114358 (miR-1206) decreased the risk of breast cancer in individuals with allele A (p = 0.01). In silico study showed that allele change was associated with a reduction in structural stability.

Therefore, the rs12976445 variant can be considered a risk factor for breast cancer, and the rs2114358 variant is a protective factor against it.

Exosomes are extracellular vesicles well known for facilitating cell-to-cell communication by distributing essential macromolecules like proteins, DNA, mRNA, lipids, and miRNA. These vesicles are abundant in fluids distributed throughout the body, including urine, blood, saliva, and even bile. They are important diagnostic tools for breast, lung, gastrointestinal cancers, etc. However, their application as cancer biomarkers has not yet been implemented in most parts of the world. In this review, we discuss how OMICs profiling of exosomes can be practiced by substituting traditional imaging or biopsy methods for cancer detection. Previous methods like extensive imaging and biopsy used for screening were expensive, mostly invasive, and could not easily provide early detection for various types of cancer. Exosomal biomarkers can be utilized for routine screening by simply collecting body fluids from the individual. We anticipate that the use of exosomes will be brought to light by the success of clinical trials investigating their potential to enhance cancer detection and treatment in the upcoming years.

Extracellular vesicles (EVs) are of growing interest in the context of screening for highly informative cancer markers. We have previously shown that uterine aspirate EVs (UA EVs) are a promising source of ovarian cancer (OC) diagnostic markers. In this study, we first conducted an integrative analysis of EV-miRNA profiles from UA, malignant ascitic fluid (AF), and a conditioned medium of cultured ascites cells (ACs). Using three software packages, we identified 79 differentially expressed miRNAs (DE-miRNAs) in UA EVs from OC patients and healthy individuals. To narrow down this panel and select miRNAs most involved in OC pathogenesis, we aligned these molecules with the DE-miRNA sets obtained by comparing the EV-miRNA profiles from OC-related biofluids with the same control. We found that 76% of the DE-miRNAs from the identified panel are similarly altered (differentially co-expressed) in AF EVs, as are 58% in AC EVs. Interestingly, the set of miRNAs differentially co-expressed in AF and AC EVs strongly overlaps (40 out of 44 miRNAs). Finally, the application of more rigorous criteria for DE assessment, combined with the selection of miRNAs that are differentially co-expressed in all biofluids, resulted in the identification of a panel of 29 miRNAs for ovarian cancer screening.

Ovarian carcinoma (OC) is ranked as the eighth most lethal gynecological cancer due to late diagnosis and high recurrence. Existing biomarkers are lacking to predict the recurrence and stratify patients who are likely to benefit from chemotherapy. MicroRNAs (miRNAs/miRs) are persistently present in humans and are capable of predicting treatment outcomes. Thus, the purpose of the study was to assess the potential of circulatory miRNAs to predict the efficacy of OC.

Newly diagnosed n = 208 OC patients were administrated neoadjuvant/adjuvant chemotherapy (taxane + platinum) after surgery. Their demographic, gynecologic, clinical parameters, response, and survival were recorded. MiR-27a, miR-182, miR-199a, miR-214, and miR-591 were taken and the expression were analyzed using real-time PCR at different treatment intervals. Further, its prognostic value (Kaplan-Meier, and Cox regression analysis) and diagnostic importance (receiver operating characteristic curve) were validated.

The mean age of patients with poorly differentiated (45.2%) serous OC was 48.69 ± 10.38. The majority experienced menarche at ≥ 12 (62.2%) with poor menstrual hygiene (81.8%) and were post-menopausal (69.4%), some were associated with high risk of survival (HR =  > 1). MiRNA signature showed three over-expression and two under-expression (miR-27a, miR-182, and miR-214; miR-199a and miR-591) in advanced OC compared to the control (P=  < 0.05). Also, a significant difference was detected at each time interval of treatment with the response (P =  ≤ 0.001) associated with resistance and overall survival (P =  ≤ 0.001) with risk (HR =  > 1). ROC analysis showed enhanced the diagnostics accuracy (< 0.001).

Our findings indicate that circulating miRNAs might be a potential minimally invasive diagnostic marker for treatment outcome and recurrence in ovarian carcinoma.

Inherited variations in DNA double-strand break (DSB) repair pathway are known to influence ovarian cancer occurrence, progression and treatment response. Despite its significance, survival-associated genetic variants within the DSB pathway remain underexplored.

In the present study, we performed a two-phase analysis of 19,290 single-nucleotide polymorphisms (SNPs) in 199 genes in the DSB repair pathway from a genome-wide association study (GWAS) dataset and explored their associations with overall survival (OS) in 1039 Han Chinese epithelial ovarian carcinoma (EOC) patients. After utilizing multivariate Cox regression analysis with bayesian false-discovery probability for multiple test correction, significant genetic variations were identified and subsequently underwent functional prediction and validation.

We discovered a significant association between poor overall survival and the functional variant GEN1 rs56070363 C > T (CT + TT vs. TT, adjusted hazard ratio (HR) = 2.50, P < 0.001). And the impact of GEN1 rs56070363 C > T on survival was attributed to its reduced binding affinity to hsa-miR-1287-5p and the resultant upregulation of GEN1 mRNA expression. Overexpression of GEN1 aggregated EOC cell proliferation, invasion and migration presumably by influencing the expression of immune inhibitory factors, thereby elevating the proportion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and then constructing an immunosuppressive tumor microenvironment.

In conclusion, GEN1 rs56070363 variant could serve as a potential predictive biomarker and chemotherapeutic target for improving the survival of EOC patients.

Ovarian cancer (OC) represents the most prevalent malignancy of the female reproductive system. Its distinguishing features include a high aggressiveness, substantial morbidity and mortality, and a lack of apparent symptoms, which collectively pose significant challenges for early detection. Given that aberrant DNA methylation events leading to altered gene expression are characteristic of numerous tumor types, there has been extensive research into epigenetic mechanisms, particularly DNA methylation, in human cancers. In the context of OC, DNA methylation is often associated with the regulation of critical genes, such as BRCA1/2 and Ras‑association domain family 1A. Methylation modifications within the promoter regions of these genes not only contribute to the pathogenesis of OC, but also induce medication resistance and influence the prognosis of patients with OC. As such, a more in‑depth understanding of DNA methylation underpinning carcinogenesis could potentially facilitate the development of more effective therapeutic approaches for this intricate disease. The present review focuses on classical tumor suppressor genes, oncogenes, signaling pathways and associated microRNAs in an aim to elucidate the influence of DNA methylation on the development and progression of OC. The advantages and limitations of employing DNA methylation in the diagnosis, treatment and prevention of OC are also discussed. On the whole, the present literature review indicates that the DNA methylation of specific genes could potentially serve as a prognostic biomarker for OC and a therapeutic target for personalized treatment strategies. Further investigations in this field may yield more efficacious diagnostic and therapeutic alternatives for patients with OC.

Cancer is one of the most serious leading causes of death in the world. Many eclectic factors are involved in cancer progression including genetic and epigenetic alongside environmental ones. In this account, the performance and fluctuations of microRNAs are significant in cancer diagnosis and treatment, particularly as diagnostic biomarkers in oncology. So, microRNAs manage and control the gene expression after transcription by mRNA degradation, or also they can inhibit their translation. Conspicuously, these molecular structures take part in controlling the cellular, physiological and pathological functions, which many of them can accomplish as tumor inhibitors or oncogenes. Relatively, Oxidative stress is defined as the inequality between the creation of reactive oxygen species (ROS) and the body's ability to detoxify the reactive mediators or repair the resulting injury. ROS and microRNAs have been recognized as main cancer promoters and possible treatment targets. Importantly, genotoxicity has been established as the primary reason for many diseases as well as several malignancies. The procedures have no obvious link with mutagenicity and influence the organization, accuracy of the information, or fragmentation of DNA. Conclusively, mutations in these patterns can lead to carcinogenesis. In this review article, we report the impressive and practical roles of microRNAs, oxidative stress, and genotoxicity in the pathobiology of cancer development in conjunction with their importance as reliable cancer biomarkers and their association with circulating miRNA, exosomes and exosomal miRNAs, RNA remodeling, DNA methylation, and other molecular elements in oncology.

Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence that clear-cell and endometrioid ovarian carcinomas (endometriosis-associated ovarian carcinoma-EAOC) may arise in endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interaction domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in phosphatidylinositol 3-kinase (PI3K) which frequently coexist. Recent studies have also suggested the simultaneous role of the PTEN tumor-suppressor gene in the early malignant transformation of endometriosis and the contribution of deficient MMR (mismatch repair) protein status in the pathogenesis of EAOC. In addition to activating and inactivating mutations in cancer driver genes, the complex pathogenesis of EAOC involves multiple other mechanisms such as the modulation of cancer driver genes via the transcriptional and post-translational (miRNA) modulation of cancer driver genes and the interplay with the inflammatory tissue microenvironment. This knowledge is being translated into the clinical management of endometriosis and EAOC. This includes the identification of the new biomarkers predictive of the risk of endometriosis and cancer, and it will shape the precision oncology treatment of EAOC.

Ovarian cancer is one of the most aggressive and significant malignant tumor forms in the female reproductive system. It is the leading cause of death among gynecological cancers owing to its metastasis. Since its preliminary disease symptoms are lacking, it is imperative to develop early diagnostic biomarkers to aid in treatment optimization and personalization. In this vein, microRNAs, which are short sequence non-coding molecules, displayed great potential as highly specific and sensitive biomarker. miRNAs have been extensively advocated and proven to serve an instrumental part in the clinical management of cancer, especially ovarian cancer, by promoting the cancer cell progression, invasion, delayed apoptosis, epithelial-mesenchymal transition, metastasis of cancer cells, chemosensitivity and resistance and disease therapy. Here, we cover our present comprehension of the most up-to-date microRNA-based approaches to detect ovarian cancer, as well as current diagnostic and treatment strategies, the role of microRNAs as oncogenes or tumor suppressor genes, and their significance in ovarian cancer progression, prognosis, and therapy.

Endometriosis is a chronic condition affecting reproductive-aged women, characterized by the growth of ectopic endometrial tissue. Despite being benign, endometriosis is associated with an increased risk of certain cancers, including endometriosis-associated ovarian cancer (EAOC). Ovarian cancer is rare, but more common in women with endometriosis, particularly endometrioid and clear-cell carcinomas. Factors such as hormonal imbalance, reproductive history, environmental exposures, and genetic predisposition contribute to the malignant transformation of endometriosis. Thus, understanding potential risk factors causing malignancy is crucial. Over the past few decades, various genetic mutations, microRNAs, as well as tumor microenvironmental factors have been identified, impacting pathways like PI3K/AKT/mTOR, DNA repair mechanisms, oxidative stress, and inflammation. Thus, this review aims to summarize molecular studies involved in EAOC pathogenesis as potential therapeutic targets. However, further research is needed to better understand the molecular and environmental factors driving EAOC development, to target the susceptibility of endometriotic lesions to malignant progression, and to identify effective therapeutic strategies.

A growing body of evidence indicates an important role of miRNAs in cancer; however, there is no definitive, convenient-to-use list of cancer-related miRNAs or miRNA genes that may serve as a reference for analyses of miRNAs in cancer. To this end, we created a list of 165 cancer-related miRNA genes called the Cancer miRNA Census (CMC). The list is based on a score, built on various types of functional and genetic evidence for the role of particular miRNAs in cancer, e.g. miRNA-cancer associations reported in databases, associations of miRNAs with cancer hallmarks, or signals of positive selection of genetic alterations in cancer. The presence of well-recognized cancer-related miRNA genes, such as MIR21, MIR155, MIR15A, MIR17 or MIRLET7s, at the top of the CMC ranking directly confirms the accuracy and robustness of the list. Additionally, to verify and indicate the reliability of CMC, we performed a validation of criteria used to build CMC, comparison of CMC with various cancer data (publications and databases), and enrichment analyses of biological pathways and processes such as Gene Ontology or DisGeNET. All validation steps showed a strong association of CMC with cancer/cancer-related processes confirming its usefulness as a reference list of miRNA genes associated with cancer.

Despite receiving first-line treatment, ovarian cancer patients continue to experience a high rate of recurrence; nearly all women with ovarian cancer develop chemoresistance and succumb to the disease. In this study, cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) were isolated from tumor-containing and normal omenta, respectively, and the downregulation of osteoglycin (OGN) in CAFs was observed. OGN overexpression in CAFs significantly inhibited ovarian cancer cell viability, DNA synthesis, and cell invasion. OGN overexpression also changed epithelial-mesenchymal transition (EMT) markers and promoted mTOR and Akt phosphorylation in ovarian cancer cells. miR-1290 targeted OGN and inhibited OGN expression. miR-1290 overexpression in CAFs significantly promoted ovarian cancer cell viability, DNA synthesis, and cell invasion. Moreover, miR-1290 overexpression in CAFs also changed EMT markers and promoted mTOR and Akt phosphorylation within ovarian carcinoma cells. Finally, when ovarian cancer cells in a conditioned medium derived from CAFs co-transduced with miR-1290 mimics and OGN-OE were cultured, the effects of miR-1290 overexpression were partially reversed by OGN overexpression. In nude mouse xenograft tumor models, OGN overexpression in CAFs suppressed tumor growth, whereas miR-1290 overexpression in CAFs increased tumor growth. In conclusion, a miRNA/mRNA axis in ovarian cancer CAFs modulating the proliferative and invasive abilities of ovarian cancer cells, possibly via the Akt/mTOR pathway, was demonstrated.

Worldwide, in 2020, an estimated 417,367 people were diagnosed with uterine cancer. Endometrial cancer accounts for more than 90% of all uterine cancers. The 15th most frequent cancer overall and the sixth most frequent cancer in women is endometrial cancer. Global ovarian cancer Incidence was diagnosed estimated at 313,959 new cases worldwide in 2020. Cervical cancer is the fourth most common malignancy in women worldwide. It has been demonstrated that sex steroid hormones (SSHs) have an essential role in regulating the susceptibility of cancer to cytotoxic therapy. Dysregulation of DNA repair contributes to genomic instability, aberrant cell survival, and cancer development as well as therapy resistance. Several crucial DNA repair components have been discovered to interact with the three main SSHs: androgen, estrogen, and progesterone. MicroRNA (miRNA) dysregulation has been associated with aberrant sex steroid hormone signaling as well as an increased risk of endometrial, cervical, and ovarian cancer. The expression of estrogen and progesterone receptors is modulated by a number of miRNAs, and it has been demonstrated that the miRNA expression profile may predict the way a patient would respond to hormone therapy. Additionally, particular miRNAs have been linked to the control of genes involved in signaling pathways connected to hormones. Recent research has shown that miRNAs can modify hormone signaling pathways and affect the expression of sex steroid hormone receptors. Our goal in this literature review is to present an overview of current knowledge regarding the role of miRNAs in cancers regulated by sex steroid hormone pathways, as well as to identify particular miRNA targets for hormonal therapy.

MicroRNAs are short non-coding RNAs that inhibit gene expression at the post-transcriptional level. Abnormal microRNA expression has been associated with different human diseases, including cancer. Epigenetic changes, mutation, transcriptional deregulation, DNA copy number abnormalities, and defects in the biogenesis machinery play an important role in abnormal microRNA expression. Modulation of microRNAs by natural agents has emerged to enhance the efficacy of conventional chemotherapy through combinatorial therapeutic approach. This review summarizes the current understanding of abnormal microRNA expression in cancer, the different cellular mechanisms of microRNA, and their prevention by natural compounds. Understanding microRNA expression patterns during cancer development may help to identify stage-specific molecular markers. Natural compounds that exert regulatory effects by modulating microRNAs can be used in better cancer chemopreventive strategies by directly targeting microRNAs or as a way to increase sensitivity to existing chemotherapy regimens.

MiRNAs play crucial roles in a broad spectrum of biological processes, both physiological and pathological. Different reports implicate miR-205 in the control of breast stem cell properties. Differential miR-205 expression has been observed in different stages of mammary gland development and maturation. However, a functional role in this process has not been clearly demonstrated. We generated an miR-205 knockout in the FVB/N mouse strain, which is viable and characterized by enhanced mammary gland development. Indeed, mammary glands of miR-205-/- female mice at different ages (1.5 and 5.5 months) show increased outgrowth and branching. This evidence is consistent with our previously reported data demonstrating the direct miR-205-mediated targeting of HER3, a master regulator of mammary gland development, and the oncosuppressive activity of this microRNA in different types of breast cancer.

The development of a robust and cost-effective sensing platform for microRNA (miRNA) is of paramount importance in detecting and monitoring various diseases. Current miRNA detection methods are marred by low accuracy, high cost, and instability. The toehold switch riboregulator has shown promising results in detecting viral RNAs integrated with the freeze-dried cell-free system (CFS). This study aimed to leverage the toehold switch technology and portability to detect miRNA in the CFS and to incorporate the exponential amplification reaction (EXPAR) to bring the detection to clinically relevant levels. We assessed various EXPAR DNA templates under different conditions to enhance the accuracy of the sensing platform. Furthermore, different structures of toehold switches were tested with either high-concentration synthetic miRNA or EXPAR product to assess sensitivity. Herein, we elucidated the mechanisms of the toehold switch and EXPAR, presented the findings of these optimizations, and discussed the potential benefits and drawbacks of their combined use.

Epithelial ovarian cancer (EOC) is one of the leading cancers in women, with high-grade serous ovarian cancer (HGSOC) being the most common and lethal subtype of this disease. A vast majority of HGSOC are diagnosed at the late stage of the disease when the treatment and total recovery chances are low. Thus, there is an urgent need for novel, more sensitive and specific methods for early and routine HGSOC clinical diagnosis. In this study, we performed miRNA expression profiling using the NanoString miRNA assay in 34 serum samples from patients with HGSOC and 36 healthy women. We identified 13 miRNAs that were differentially expressed (DE). For additional exploration of expression patterns correlated with HGSOC, we performed weighted gene co-expression network analysis (WGCNA). As a result, we showed that the module most correlated with tumour size, nodule and metastasis contained 8 DE miRNAs. The panel including miR-1246 and miR-150-5p was identified as a signature that could discriminate HGSOC patients with AUCs of 0.98 and 1 for the training and test sets, respectively. Furthermore, the above two-miRNA panel had an AUC = 0.946 in the verification cohorts of RT-qPCR data and an AUC = 0.895 using external data from the GEO public database. Thus, the model we developed has the potential to markedly improve the diagnosis of ovarian cancer.

The term "gynecologic cancer" pertains to neoplasms impacting the reproductive tissues and organs of women encompassing the endometrium, vagina, cervix, uterus, vulva, and ovaries. The progression of gynecologic cancer is linked to various molecular mechanisms. Historically, cancer research primarily focused on protein-coding genes. However, recent years have unveiled the involvement of non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs (LncRNAs), and circular RNAs, in modulating cellular functions within gynecological cancer. Substantial evidence suggests that ncRNAs may wield a dual role in gynecological cancer, acting as either oncogenic or tumor-suppressive agents. Numerous clinical trials are presently investigating the roles of ncRNAs as biomarkers and therapeutic agents. These endeavors may introduce a fresh perspective on the diagnosis and treatment of gynecological cancer. In this overview, we highlight some of the ncRNAs associated with gynecological cancers.

Gynecologic cancer is a significant cause of death in women worldwide, with cervical cancer, ovarian cancer, and endometrial cancer being among the most well-known types. The initiation and progression of gynecologic cancers involve a variety of biological functions, including angiogenesis and metastasis-given that death mostly occurs from metastatic tumors that have invaded the surrounding tissues. Therefore, understanding the molecular pathways underlying gynecologic cancer metastasis is critical for enhancing patient survival and outcomes. Recent research has revealed the contribution of numerous non-coding RNAs (ncRNAs) to metastasis and invasion of gynecologic cancer by affecting specific cellular pathways. This review focuses on three types of gynecologic cancer (ovarian, endometrial, and cervical) and three kinds of ncRNAs (long non-coding RNAs, microRNAs, and circular RNAs). We summarize the detailed role of non-coding RNAs in the different pathways and molecular interactions involved in the invasion and metastasis of these cancers.

Ovarian cancer (OC) is described as a heterogeneous complex condition with high mortality, weak prognosis, and late-stage presentation. OC has several subgroups based on different indices, like the origin and histopathology. The current treatments against OC include surgery followed by chemotherapy and radiotherapy; however, these methods have represented diverse side effects without enough effectiveness on OC. Recently, mesenchymal stem cell (MSC)-based therapy has acquired particular attention for treating diverse problems, such as cancer. These multipotent stem cells can be obtained from different sources, such as the umbilical cord, adipose tissues, bone marrow, and placenta, and their efficacy has been investigated against OC. Hence, in this narrative review, we aimed to review and discuss the present studies about the effects of various sources of MSCs on OC with a special focus on involved mechanisms.

MicroRNAs (miRNAs) are non-coding RNAs with only 20-22 nucleic acids that inhibit gene transcription and translation by binding to mRNA. MiRNAs have a diverse set of target genes and can alter most physiological processes, including cell cycle checkpoints, cell survival, and cell death mechanisms, affecting the growth, development, and invasion of various cancers, including gliomas. So optimum management of miRNA expression is essential for preserving a normal biological environment. Due to their small size, stability, and capability of specifically targeting oncogenes, miRNAs have emerged as a promising marker and new biopharmaceutical targeted therapy for glioma patients. This review focuses on the most common miRNAs associated with gliomagenesis and development by controlling glioma-determining markers such as angiogenesis. We also summarized the recent research about miRNA effects on signaling pathways, their mechanistic role and cellular targets in the development of gliomas angiogenesis. Strategies for miRNA-based therapeutic targets, as well as limitations in clinical applications, are also discussed.

Ovarian cancer is the second most fatal gynecological cancer. Early detection, which could be achieved through widespread screening, has not yet had an impact on mortality. The aim of our pilot study was to investigate the expression of miRNAs analyzed by a human miRNA microarray chip in urine and serum of patients with ovarian cancer. We analyzed three serum and three urine samples from healthy donors and five serum and five urine samples from patients with ovarian cancer taken at first diagnosis, before any treatment. We selected the seven miRNAs with the highest expression fold change in the microarray chip (cancer vs. control) in urine and serum, for validation by qPCR. We were able to validate two of the seven miRNAs in serum. In contrast to these findings, we were able to validate all of the top seven miRNAs identified in urine using qPCR. The top seven miRNAs in urine identified by microarray chip showed significantly greater differences in expression between patients with ovarian cancer and healthy donors compared to serum. Based on our finding, we can suggest that urine as a biomaterial is more suitable than serum for miRNA profiling by microarray chip in the search for new biomarkers in ovarian cancer.

Ovarian cancer is a deadly disease that affects thousands of women worldwide. Integrins, transmembrane receptors that mediate cell adhesion and signaling, play important roles in ovarian cancer progression, metastasis, and drug resistance. Dysregulated expression of integrins is implicated in various cellular processes, such as cell migration, invasion, and proliferation. Emerging evidence suggests that microRNAs (miRNAs) can regulate integrin expression and function, thus affecting various physiological and pathological processes, including ovarian cancer. In this article, we review the current understanding of integrin-mediated cellular processes in ovarian cancer and the roles of miRNAs in regulating integrins. We also discuss the therapeutic potential of targeting miRNAs that regulate integrins for the treatment of ovarian cancer. Targeting miRNAs that regulate integrins or downstream signaling pathways of integrins may provide novel therapeutic strategies for inhibiting integrin-mediated ovarian cancer progression.

Ovarian cancer, a perilous form of cancer affecting the female reproductive system, exhibits intricate communication networks that contribute to its progression. This study aims to identify crucial molecular abnormalities linked to the disease to enhance diagnostic and therapeutic strategies. In particular, we investigate the role of microRNAs (miRNAs) as diagnostic biomarkers and explore their potential in treating ovarian cancer. By targeting miRNAs, which can influence multiple pathways and genes, substantial therapeutic benefits can be attained. In this review we want to shed light on the promising application of miRNA-based interventions and provide insights into the specific miRNAs implicated in ovarian cancer pathogenesis.

Post-translational and epigenetic regulation are important mechanisms controlling functions of genes and proteins. Although the "classic" estrogen receptors (ERs) have been acknowledged to function in mediating estrogen effects via transcriptional mechanisms, estrogenic agents modulate the turnover of several proteins via post-transcriptional and post-translational pathways including epigenetics. For instance, the metabolic and angiogenic action of G-protein coupled estrogen receptor (GPER) in vascular endothelial cells has been recently elucidated. By interacting with GPER, 17β-estradiol and the GPER agonist G1 enhance endothelial stability of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and capillary tube formation by increasing ubiquitin-specific peptidase 19 levels, thereby reducing PFKFB3 ubiquitination and proteasomal degradation. In addition to ligands, the functional expression and trafficking of ERs can be modulated by post-translational modification, including palmitoylation. MicroRNAs (miRNAs), the most abundant form of endogenous small RNAs in humans, regulate multiple target genes and are at the center of the multi-target regulatory network. This review also discusses the emerging evidence of how miRNAs affect glycolytic metabolism in cancer, as well as their regulation by estrogens. Restoring dysregulated miRNA expression represents a promising strategy to counteract the progression of cancer and other disease conditions. Accordingly, estrogen post-transcriptional regulatory and epigenetic mechanisms represent novel targets for pharmacological and nonpharmacological intervention for the treatment and prevention of hormone-sensitive noncommunicable diseases, including estrogen-sensitive cancers of the reproductive system in women. SIGNIFICANCE STATEMENT: The effects of estrogen are mediated by several mechanisms that are not limited to the transcriptional regulation of target genes. Slowing down the turnover of master regulators of metabolism by estrogens allows cells to rapidly adapt to environmental cues. Identification of estrogen-targeted microRNAs may lead to the development of novel RNA therapeutics that disrupt pathological angiogenesis in estrogen-dependent cancers.

Bisphenol A (BPA) is a ubiquitous environmental xenobiotic impacting millions of people worldwide. BPA has long been proposed to promote ovarian carcinogenesis, but the detrimental mechanistic target remains unclear. Cancer stem cells (CSCs) are considered as the trigger of tumour initiation and progression. Here, we show for the first time that nanomolar (environmentally relevant) concentration of BPA can markedly increase the formation and expansion of ovarian CSCs concomitant. This effect is observed in both oestrogen receptor (ER)-positive and ER-defective ovarian cancer cells, suggesting that is independent of the classical ERs. Rather, the signal is mediated through alternative ER G-protein-coupled receptor 30 (GPR30), but not oestrogen-related receptor α and γ. Moreover, we report a novel role of BPA in the regulation of Exportin-5 that led to dysregulation of microRNA biogenesis through miR-21. The use of GPR30 siRNA or antagonist to inhibit GPR30 expression or activity, respectively, resulted in significant inhibition of ovarian CSCs. Similarly, the CSCs phenotype can be reversed by expression of Exportin-5 siRNA. These results identify for the first time non-classical ER and microRNA dysregulation as novel mediators of low, physiological levels of BPA function in CSCs that may underlie its significant tumour-promoting properties in ovarian cancer.

Hyperthermic intraperitoneal administration of chemotherapy (HIPEC) increases local drug concentrations and reduces systemic side effects associated with prolonged adjuvant intraperitoneal exposure in patients affected by either peritoneal malignancies or metastatic diseases originating from gastric, colon, kidney, and ovarian primary tumors. Mechanistically, the anticancer effects of HIPEC have been poorly explored. Herein we documented that HIPEC treatment promoted miR-145-5p expression paired with a significant downregulation of its oncogenic target genes c-MYC, EGFR, OCT4, and MUC1 in a pilot cohort of patients with ovarian peritoneal metastatic lesions. RNA sequencing analyses of ovarian peritoneal metastatic nodules from HIPEC treated patients unveils HSF-1 as a transcriptional regulator factor of miR-145-5p expression. Notably, either depletion of HSF-1 expression or chemical inhibition of its transcriptional activity impaired miR-145-5p tumor suppressor activity and the response to cisplatin in ovarian cancer cell lines incubated at 42 °C. In aggregate, our findings highlight a novel transcriptional network involving HSF-1, miR145-5p, MYC, EGFR, MUC1, and OCT4 whose proper activity contributes to HIPEC anticancer efficacy in the treatment of ovarian metastatic peritoneal lesions.