Thymoquinone Potentially Modulates the Expression of Key Onco- and Tumor Suppressor miRNAs in Prostate and Colon Cancer Cell Lines: Insights from PC3 and HCT-15 Cells.

Prostate cancer (PC) and colon cancer significantly contribute to global cancer-related morbidity and mortality. Thymoquinone (TQ), a naturally occurring phytochemical found in black cumin, has shown potential as an anticancer compound. This study aimed to investigate the effects of TQ on the expression profile of key tumor suppressor and onco-suppressor miRNAs in PC3 prostate cancer cells and HCT-15 colon cancer cells. Cell viability assays revealed that TQ inhibited the growth of both cell lines in a dose-dependent manner, with IC50 values of approximately 82.59 µM for HCT-15 and 55.83 µM for PC3 cells. Following TQ treatment at the IC50 concentrations, miRNA expression analysis demonstrated that TQ significantly downregulated miR-21-5p expression in HCT-15 cells and upregulated miR-34a-5p, miR-221-5p, miR-17-5p, and miR-21-5p expression in PC3 cells. However, no significant changes were observed in the expression levels of miR-34a-5p and miR-200a-5p in HCT-15 cells. The current findings suggest that TQ might exert its antiproliferative effects by modulating specific tumor suppressor and onco-suppressor miRNAs in prostate and colon cancer cells. Further investigations are warranted to elucidate the precise underlying mechanisms and to explore the therapeutic potential of TQ in cancer treatment. To the best of our knowledge, this is the first report regarding the effect of TQ on the miRNA expression profile in colon and prostate cancer cell lines.

Exploring the Potential Role of Circulating microRNAs as Biomarkers for Predicting Clinical Response to Neoadjuvant Therapy in Breast Cancer.

Breast cancer (BC) is a leading cause of cancer-related deaths among women worldwide. Neoadjuvant therapy (NAT) is increasingly being used to reduce tumor burden prior to surgical resection. However, current techniques for assessing tumor response have significant limitations. Additionally, drug resistance is commonly observed, raising a need to identify biomarkers that can predict treatment sensitivity and survival outcomes. Circulating microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have been shown to play a significant role in cancer progression as tumor inducers or suppressors. The expression of circulating miRNAs has been found to be significantly altered in breast cancer patients. Moreover, recent studies have suggested that circulating miRNAs can serve as non-invasive biomarkers for predicting response to NAT. Therefore, this review provides a brief overview of recent studies that have demonstrated the potential of circulating miRNAs as biomarkers for predicting the clinical response to NAT in BC patients. The findings of this review will strengthen future research on developing miRNA-based biomarkers and their translation into medical practice, which could significantly improve the clinical management of BC patients undergoing NAT.

Regulatory mechanisms of microRNAs in endocrine disorders and their therapeutic potential.

MicroRNAs (miRNAs) are small endogenous non-coding RNA molecules capable of regulating gene expression at the post-transcriptional level either by translational inhibition or mRNA degradation and have recently been importantly related to the diagnosis and prognosis of the most relevant endocrine disorders. The endocrine system comprises various highly vascularized ductless organs regulating metabolism, growth and development, and sexual function. Endocrine disorders constitute the fifth principal cause of death worldwide, and they are considered a significant public health problem due to their long-term effects and negative impact on the patient's quality of life. Over the last few years, miRNAs have been discovered to regulate various biological processes associated with endocrine disorders, which could be advantageous in developing new diagnostic and therapeutic tools. The present review aims to provide an overview of the most recent and significant information regarding the regulatory mechanism of miRNAs during the development of the most relevant endocrine disorders, including diabetes mellitus, thyroid diseases, osteoporosis, pituitary tumors, Cushing's syndrome, adrenal insufficiency and multiple endocrine neoplasia, and their potential implications as disease biomarkers.

MicroRNA-mediated regulation of key signaling pathways in hepatocellular carcinoma: A mechanistic insight.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. The molecular pathogenesis of HCC varies due to the different etiologies and genotoxic insults. The development of HCC is characterized by complex interactions between several etiological factors that result in genetic and epigenetic changes in proto-onco and/or tumor suppressor genes. MicroRNAs (miRNAs) are short non-coding RNAs that also can act as oncomiRs or tumor suppressors regulating the expression of cancer-associated genes post-transcriptionally. Studies revealed that several microRNAs are directly or indirectly involved in cellular signaling, and dysregulation of those miRNAs in the body fluids or tissues potentially affects key signaling pathways resulting in carcinogenesis. Therefore, in this mini-review, we discussed recent progress in microRNA-mediated regulation of crucial signaling networks during HCC development, concentrating on the most relevant ones such as PI3K/Akt/mTOR, Hippo-YAP/TAZ, and Wnt/ß-catenin, which might open new avenues in HCC management.

Recent insights into the microRNA and long non-coding RNA-mediated regulation of stem cell populations.

Stem cells are undifferentiated cells that have multi-lineage differentiation. The transition from self-renewal to differentiation requires rapid and extensive gene expression alterations. Since different stem cells exhibit diverse non-coding RNAs (ncRNAs) expression profiles, the critical roles of ncRNAs in stem cell reprogramming, pluripotency maintenance, and differentiation have been widely investigated over the past few years. Hence, in this current review, the two main categories of ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are discussed. While the primary way by which miRNAs restrict mRNA transcription is through miRNA-mRNA interaction, lncRNAs have a wide range of effects on mRNA functioning, including interactions with miRNAs. Both of these ncRNAs participate in the post-transcriptional regulation of crucial biological mechanisms, such as cell cycle regulation, apoptosis, aging, and cell fate decisions. These findings shed light on a previously unknown aspect of gene regulation in stem cell fate determination and behavior. Overall, we summarized the key roles of miRNAs (including exosomal miRNAs) and lncRNAs in the regulation of stem cell populations, such as cardiac, hematopoietic, mesenchymal, neural, and spermatogonial, as well ncRNAs' influence on malignancy through modulating cancer stem cells, which might significantly contribute to clinical stem cell therapy and in regenerative medicine.

A Brief Review on the Regulatory Roles of MicroRNAs in Cystic Diseases and Their Use as Potential Biomarkers.

miRNAs are small endogenous conserved non-coding RNA molecules that regulate post-transcriptional gene expression through mRNA degradation or translational inhibition, modulating nearly 60% of human genes. Cystic diseases are characterized by the presence of abnormal fluid-filled sacs in the body, and though most cysts are benign, they can grow inside tumors and turn malignant. Recent evidence has revealed that the aberrant expression of a number of miRNAs present in extracellular fluids, including plasma or serum, urine, saliva, follicular fluid, and semen, contribute to different cystic pathologies. This review aims to describe the role of different miRNAs in three worldwide relevant cystic diseases: polycystic ovarian syndrome (PCOS), polycystic kidney disease (PKD), and pancreatic cyst tumors (PCTs), as well as their potential use as novel biomarkers.

Phytochemicals mediated modulation of microRNAs and long non-coding RNAs in cancer prevention and therapy.

MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two main categories of noncoding RNAs (ncRNAs) that can influence essential biological functions in various ways, as well as their expression and function are tightly regulated in physiological homeostasis. Additionally, the dysregulation of these ncRNAs seems to be crucial to the pathogenesis of human diseases. The latest findings indicate that ncRNAs execute vital roles in cancer initiation and progression, and the cancer phenotype can be reversed by modulating their expression. Available scientific discoveries suggest that phytochemicals such as polyphenols, alkaloids, terpenoids, and organosulfur compounds can significantly modulate multiple cancer-associated miRNAs and lncRNAs, thereby inhibiting cancer initiation and development. However, despite promising outcomes of experimental research, only a few clinical trials are currently being conducted to evaluate the therapeutic effectiveness of these compounds. Nevertheless, understanding phytochemical-mediated ncRNA regulation in cancer and the underlying molecular mechanisms on tumor pathophysiology can aid in the development of novel therapeutic strategies to combat this deadly disease.

Human microRNAs in host-parasite interaction: a review.

MicroRNAs (miRNAs) are a group of small noncoding RNA molecules with significant capacity to regulate the gene expression at the post-transcriptional level in a sequence-specific manner either through translation repression or mRNA degradation triggering a fine-tuning biological impact. They have been implicated in several processes, including cell growth and development, signal transduction, cell proliferation and differentiation, metabolism, apoptosis, inflammation, and immune response modulation. However, over the last few years, extensive studies have shown the relevance of miRNAs in human pathophysiology. Common human parasitic diseases, such as Malaria, Leishmaniasis, Amoebiasis, Chagas disease, Schistosomiasis, Toxoplasmosis, Cryptosporidiosis, Clonorchiasis, and Echinococcosis are the leading cause of death worldwide. Thus, identifying and characterizing parasite-specific miRNAs and their host targets, as well as host-related miRNAs, are important for a deeper understanding of the pathophysiology of parasite-specific diseases at the molecular level. In this review, we have demonstrated the impact of human microRNAs during host-parasite interaction as well as their potential to be used for diagnosis and prognosis purposes.