Advanced strategies of targeting circular RNAs as therapeutic approaches in colorectal cancer drug resistance.

Colorectal cancer (CRC) stands second in terms of mortality and third among the highest prevalent kinds of cancer globally. CRC prevalence is rising in moderately and poorly developed regions and is greater in economically advanced regions. Despite breakthroughs in targeted therapy, resistance to chemotherapeutics remains a significant challenge in the long-term management of CRC. Circular RNAs (circRNAs) have been involved in growing cancer therapy resistance, particularly in CRC, according to an increasing number of studies in recent years. CircRNAs are one of the novel subclasses of non-coding RNAs, previously thought of as viroid. According to studies, circRNAs have been recommended as biological markers for therapeutic targets and diagnostic and prognostic purposes. That is particularly notable given that the expression of circRNAs has been linked to the hallmarks of CRC since they are responsible for drug resistance in CRC patients; thereby, circRNAs are significant for chemotherapy failure. Moreover, knowledge concerning circRNAs remains relatively unclear despite using all these advanced techniques. Here, in this study, we will go over the most recent published work to highlight the critical roles of circRNAs in CRC development and drug resistance and highlight the main strategies to overcome drug resistance to improve clinical outcomes.

CRISPR/Cas9 gene editing: a novel strategy for fighting drug resistance in respiratory disorders.

Respiratory disorders are among the conditions that affect the respiratory system. The healthcare sector faces challenges due to the emergence of drug resistance to prescribed medications for these illnesses. However, there is a technology called CRISPR/Cas9, which uses RNA to guide DNA targeting. This technology has revolutionized our ability to manipulate and visualize the genome, leading to advancements in research and treatment development. It can effectively reverse epigenetic alterations that contribute to drug resistance. Some studies focused on health have shown that targeting genes using CRISPR/Cas9 can be challenging when it comes to reducing drug resistance in patients with respiratory disorders. Nevertheless, it is important to acknowledge the limitations of this technology, such as off-target effects, immune system reactions to Cas9, and challenges associated with delivery methods. Despite these limitations, this review aims to provide knowledge about CRISPR/Cas9 genome editing tools and explore how they can help overcome resistance in patients with respiratory disorders. Additionally, this study discusses concerns related to applications of CRISPR and provides an overview of successful clinical trial studies.

Advanced approaches of the use of circRNAs as a replacement for cancer therapy.

Cancer is a broad name for a group of diseases in which abnormal cells grow out of control and are characterized by their complexity and recurrence. Although there has been progress in cancer therapy with the entry of precision medicine and immunotherapy, cancer incidence rates have increased globally. Non-coding RNAs in the form of circular RNAs (circRNAs) play crucial roles in the pathogenesis, clinical diagnosis, and therapy of different diseases, including cancer. According to recent studies, circRNAs appear to serve as accurate indicators and therapeutic targets for cancer treatment. However, circRNAs are promising candidates for cutting-edge cancer therapy because of their distinctive circular structure, stability, and wide range of capabilities; many challenges persist that decrease the applications of circRNA-based cancer therapeutics. Here, we explore the roles of circRNAs as a replacement for cancer therapy, highlight the main challenges facing circRNA-based cancer therapies, and discuss the key strategies to overcome these challenges to improve advanced innovative therapies based on circRNAs with long-term health effects.

Mesenchymal stromal cells (MSCs) as a therapeutic agent of inflammatory disease and infectious COVID-19 virus: live or dead mesenchymal?

The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various sources, such as adipose tissue, bone marrow, peripheral blood, inner organs, and neonatal tissues. The regulation of inflammatory cytokines is crucial in inhibiting inflammatory diseases and promoting the presence of anti-inflammatory cytokines for infectious diseases. MSCs have been employed as therapeutic agents for tissue damage, diabetes, autoimmune diseases, and COVID-19 patients. Our research aimed to determine whether live or dead MSCs are more suitable for the treatment of COVID-19 patients. Our findings concluded that dead MSCs, when directly administered to the patient, offer advantages over viable MSCs due to their extended presence and higher levels of immune regulation, such as T-reg, B-reg, and IL-10, compared to live MSCs. Additionally, dead and apoptotic MSCs are likely to be more readily captured by monocytes and macrophages, prolonging their presence compared to live MSCs.

Role of circular RNAs and gut microbiome in gastrointestinal cancers and therapeutic targets.

Gastrointestinal cancers are a huge worldwide health concern, which includes a wide variety of digestive tract cancers. Circular RNAs (circRNAs), a kind of non-coding RNA (ncRNAs), are a family of single-stranded, covalently closed RNAs that have become recognized as crucial gene expression regulators, having an impact on several cellular functions in cancer biology. The gut microbiome, which consists of several different bacteria, actively contributes to the regulation of host immunity, inflammation, and metabolism. CircRNAs and the gut microbiome interact significantly to greatly affect the growth of GI cancer. Several studies focus on the complex functions of circRNAs and the gut microbiota in GI cancers, including esophageal cancer, colorectal cancer, gastric cancer, hepatocellular cancer, and pancreatic cancer. It also emphasizes how changed circRNA expression profiles and gut microbiota affect pathways connected to malignancy as well as how circRNAs affect hallmarks of gastrointestinal cancers. Furthermore, circRNAs and gut microbiota have been recommended as biological markers for therapeutic targets as well as diagnostic and prognostic purposes. Targeting circRNAs and the gut microbiota for the treatment of gastrointestinal cancers is also being continued to study. Despite significant initiatives, the connection between circRNAs and the gut microbiota and the emergence of gastrointestinal cancers remains poorly understood. In this study, we will go over the most recent studies to emphasize the key roles of circRNAs and gut microbiota in gastrointestinal cancer progression and therapeutic options. In order to create effective therapies and plan for the future gastrointestinal therapy, it is important to comprehend the functions and mechanisms of circRNAs and the gut microbiota.

LncRNA SNHG12: A budding star in human diseases.

Small nucleolar RNA host gene 12 (SNHG12) is a long non-coding RNA (lncRNA) that contributes in a variety of human pathologies. This lncRNAs acts as molecular sponge for various miRNAs, namely miR-200c-5p, miR-129-5p, miR-30a-3p, miR-195, miR-133b, miR-199a/b-5p, miR-320b, miR-16, miR-15a, miR-218-5p, miR-320 and a number of other miRNAs. Through this mechanism, SNHG12 can affect activity of HIF-1α, Wnt/ß-catenin, VEGF, PI3K/AKT/mTOR, PTEN, NF-κB and ERK-1/2 signaling. SNHG12 can affect pathogenesis of several disorders, including those arising from genitourinary, gastrointestinal, pulmonary, central nervous and cardiovascular systems. These effects have been best characterized in the context of cancer where it can be used as a possible diagnostic and prognostic marker. In order to summarize the role of this lncRNA in human disorders, particularly cancer and highlight its potential application in biomedical studies, we designed the current review. We also emphasized on its diagnostic and prognostic roles.

New insights of miRNA molecular mechanisms in breast cancer brain metastasis and therapeutic targets.

Brain metastases in breast cancer (BC) patients are often associated with a poor prognosis. Recent studies have uncovered the critical roles of miRNAs in the initiation and progression of BC brain metastasis, highlighting the disease's underlying molecular pathways. miRNA-181c, miRNA-10b, and miRNA-21, for example, are all overexpressed in BC patients. It has been shown that these three miRNAs help tumors grow and metastasize by targeting genes that control how cells work. On the other hand, miRNA-26b5p, miRNA-7, and miRNA-1013p are all downregulated in BC brain metastasis patients. They act as tumor suppressors by controlling the expression of genes related to cell adhesion, angiogenesis, and invasion. Therapeutic miRNA targeting has considerable promise in treating BC brain metastases. Several strategies have been proposed to modulate miRNA expression, including miRNA-Mimics, antagomirs, and small molecule inhibitors of miRNA biogenesis. This review discusses the aberrant expression of miRNAs and metastatic pathways that lead to the spread of BC cells to the brain. It also explores miRNA therapeutic target molecular mechanisms and BC brain metastasis challenges with advanced strategies. The targeting of certain miRNAs opens a new door for the development of novel therapeutic approaches for this devastating disease.

Role of long non-coding RNAs and TGF-ß signaling in the regulation of breast cancer pathogenesis and therapeutic targets.

The cytokine known as transforming growth factor (TGF) is essential for cell development, differentiation, and apoptosis in BC. TGF-ß dysregulation can either promote or inhibit tumor development, and it is a key signaling pathway in BC spread. A recently identified family of ncRNAs known as lncRNAs has received a great deal of effort and is an important regulator of many cellular processes, including transcription of genes, chromatin remodeling, progression of the cell cycle, and posttranscriptional processing. Furthermore, both TGF-ß signaling and lncRNAs serve as important early-stage biomarkers for BC diagnosis and prognosis and also play a significant role in BC drug resistance. According to recent studies, lncRNAs can regulate TGF-ß by modulating its cofactors in BC. However, the particular functions of lncRNAs and the TGF-ß pathway in controlling BC progression are not well understood yet. This review explores the lncRNAs' functional properties in BC as tumor suppressors or oncogenes in the regulation of genes, with a focus on dysregulated TGF-ß signaling. Further, we emphasize the functional roles of lncRNAs and TGF-ß pathway in the progression of BC to discover new treatment strategies and better comprehend the fundamental cellular pathways.

Current landscape of miRNAs and TGF-ß signaling in lung cancer progression and therapeutic targets.

Lung cancer (LC) is the primary reason for cancer-associated fatalities globally. Due to both tumor-suppressing and tumor-promoting activities, the TGF-ß family of growth factors is extremely essential to tumorigenesis. A non-coding single-stranded short RNA called microRNA (miRNA), which is made up of about 22 nt and is encoded by endogenous genes, can control normal and pathological pathways in various kinds of cancer, including LC. Recent research demonstrated that the TGF-ß signaling directly can affect the synthesis of miRNAs through suppressor of mothers against decapentaplegic (SMAD)-dependent activity or other unidentified pathways, which could generate allostatic feedback as a result of TGF-ß signaling stimulation and ultimately affect the destiny of cancer tissues. In this review, we emphasize the critical functions of miRNAs in lung cancer progression and, more critically, how they affect the TGF-ß signaling pathway, and explore the role of both the TGF-ß signaling pathway and miRNAs as potential therapeutic targets for improving the treatments of LC patients.

Exosomal non-coding RNAs: Blueprint in colorectal cancer metastasis and therapeutic targets.

Colorectal cancer (CRC) is ranked as the world's third-most prevalent cancer, and metastatic CRC considerably increases cancer-related fatalities globally. A number of complex mechanisms that are strictly controlled at the molecular level are involved in metastasis, which is the primary reason for death in people with CRC. Recently, it has become clear that exosomes, which are small extracellular vesicles released by non-tumorous and tumorigenic cells, play a critical role as communication mediators among tumor microenvironment (TME). To facilitate communication between the TME and cancer cells, non-coding RNAs (ncRNAs) play a crucial role and are recognized as potent regulators of gene expression and cellular processes, such as metastasis and drug resistance. NcRNAs are now recognized as potent regulators of gene expression and many hallmarks of cancer, including metastasis. Exosomal ncRNAs, like miRNAs, circRNAs, and lncRNAs, have been demonstrated to influence a number of cellular mechanisms that contribute to CRC metastasis. However, the molecular mechanisms that link exosomal ncRNAs with CRC metastasis are not well understood. This review highlights the essential roles that exosomal ncRNAs play in the progression of CRC metastatic disease and explores the therapeutic choices that are open to patients who have CRC metastases. However, exosomal ncRNA treatment strategy development is still in its early phases; consequently, additional investigation is required to improve delivery methods and find novel therapeutic targets as well as confirm the effectiveness and safety of these therapies in preclinical and clinical contexts.

Targeting miRNA by CRISPR/Cas in cancer: advantages and challenges.

Clustered regulatory interspaced short palindromic repeats (CRISPR) has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last decade. In the study of cancer, the CRISPR/CRISPR-associated protein (Cas) system opens new avenues into issues that were once unknown in our knowledge of the noncoding genome, tumor heterogeneity, and precision medicines. CRISPR/Cas-based gene-editing technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs (miRNAs). However, the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other abnormalities. This study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer therapy. Furthermore, we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them.

A review on the role of HAND2-AS1 in cancer.

HAND2 antisense RNA 1 (HAND2-AS1) is a newly recognized lncRNA encoded by a gene on 4q34.1. This lncRNA has 10 exons and is predicted to have a positive effect on expression of certain genes. HAND2-AS1 is mainly considered as a tumor suppressive lncRNA in different tissues. Moreover, HAND2-AS1 has been shown to regulate expression of several targets with possible roles in the carcinogenesis through serving as a sponge for miRNAs. This lncRNA can also influence activity of BMP, TGF-ß1, JAK/STAT and PI3K/Akt pathways. Down-regulation of HAND2-AS1 in tumor tissues has been associated with larger tumor size, higher tumor grade, higher chance of metastasis and poor clinical outcome. The present study aims at summarization of the impact of HAND2-AS1 in the carcinogenesis and its potential in cancer diagnosis or prediction of cancer prognosis.

Dysregulation of non-coding RNAs in Wilms tumor.

Wilms tumor (WT) as the most frequent pediatric tumor of kidney has been shown to be associated with dysregulation of non-coding RNAs. miR-200c, miR-155-5p, miR-1180, miR-22-3p, miR-483-5p, miR-140-5p, miR-92a-3p, miR-483-3p, miR-572, miR-539 and miR-613 are among dysregulated miRNAs in this tumor. Moreover, a number of long non-coding RNAs such as CRNDE, XIST, SNHG6, MEG3, LINC00667, MEG8, DLGAP1-AS2 and SOX21-AS1 have been shown to be dysregulated in WT. Finally, distinct studies have reported down-regulation of circCDYL and up-regulation of circ0093740 and circSLC7A6 in this tumor. Dysregulation of these transcripts represents a new avenue for identification of the pathetiology of this pediatric tumor as well as design of targeted therapies.

MiRNA-93: a novel signature in human disorders and drug resistance.

miRNA-93 is a member of the miR-106b-25 family and is encoded by a gene on chromosome 7q22.1. They play a role in the etiology of various diseases, including cancer, Parkinson's disease, hepatic injury, osteoarthritis, acute myocardial infarction, atherosclerosis, rheumatoid arthritis, and chronic kidney disease. Different studies have found that this miRNA has opposing roles in the context of cancer. Recently, miRNA-93 has been downregulated in breast cancer, gastric cancer, colorectal cancer, pancreatic cancer, bladder cancer, cervical cancer, and renal cancer. However, miRNA-93 is up-regulated in a wide variety of malignancies, such as lung, colorectal, glioma, prostate, osteosarcoma, and hepatocellular carcinoma. The aim of the current review is to provide an overview of miRNA-93's function in cancer disorder progression and non-cancer disorders, with a focus on dysregulated signaling pathways. We also give an overview of this miRNA's function as a biomarker of prognosis in cancer and emphasize how it contributes to drug resistance based on in vivo, in vitro, and human studies. Video Abstract.

A review on the role of long non-coding RNA prostate androgen-regulated transcript 1 (PART1) in the etiology of different disorders.

LncRNA prostate androgen-regulated transcript 1 (PART1) is an important lncRNA in the carcinogenesis whose role has been firstly unraveled in prostate cancer. Expression of this lncRNA is activated by androgen in prostate cancer cells. In addition, this lncRNA has a role in the pathogenesis intervertebral disc degeneration, myocardial ischemia-reperfusion injury, osteoarthritis, osteoporosis and Parkinson's disease. Diagnostic role of PART1 has been assessed in some types of cancers. Moreover, dysregulation of PART1 expression is regarded as a prognostic factor in a variety of cancers. The current review provides a concise but comprehensive summary of the role of PART1 in different cancers and non-malignant disorders.

Exosomal circular RNAs: New player in breast cancer progression and therapeutic targets.

Breast cancer is the most prevalent type of malignancy among women. Exosomes are extracellular vesicles of cell membrane origin that are released via exocytosis. Their cargo contains lipids, proteins, DNA, and different forms of RNA, including circular RNAs. Circular RNAs are new class of non-coding RNAs with a closed-loop shape involved in several types of cancer, including breast cancer. Exosomes contained a lot of circRNAs which are called exosomal circRNAs. By interfering with several biological pathways, exosomal circRNAs can have either a proliferative or suppressive role in cancer. The involvement of exosomal circRNAs in breast cancer has been studied with consideration to tumor development and progression as well as its effects on therapeutic resistance. However, its exact mechanism is still unclear, and there have not been available clinical implications of exo-circRNAs in breast cancer. Here, we highlight the role of exosomal circRNAs in breast cancer progression and to highlight the most recent development and potential of circRNAas therapeutic targets and diagnostics for breast cancer.

Exosomal circular RNA: a signature for lung cancer progression.

Membrane vesicles having a diameter of 30-150 nm are known as exosomes. Several cancer types secrete exosomes, which may contain proteins, circular RNAs (circRNAs), microRNAs, or DNA. CircRNAs are endogenous RNAs that do not code for proteins and can create continuous and covalently closed loops. In cancer pathogenesis, especially metastasis, exosomal circRNAs (exo-circRNAs) have a crucial role mainly due to the frequently aberrant expression levels within tumors. However, neither the activities nor the regulatory mechanisms of exo-circRNAs in advancing lung cancer (LC) are obvious. A better understanding of the regulation and network connections of exo-circRNAs will lead to better treatment for LCs. The main objective of the current review is to highlight the functions and mechanisms of exo-circRNAs in LC and assess the relationships between exo-circRNA dysregulation and LC progression. In addition, underline the possible therapeutic targets based on exo-circRNA modulating.