Project description:The high incidence of breast cancer (BC) is linked to metastasis, facilitated by tumor angiogenesis. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to the tumor development and angiogenesis process in different types of cancer, including BC. There's increasing evidence showed that various miRNAs play a significant role in disease processes; specifically, they are observed and over-expressed in a wide range of diseases linked to the angiogenesis process. However, more studies are required to reach the best findings and identify the link among miRNA expression, angiogenic pathways, and immune response-related genes to find new therapeutic targets. Here, we summarized the recent updates on miRNA signatures and their cellular targets in the development of breast tumor angiogenetic and discussed the strategies associated with miRNA-based therapeutic targets as anti-angiogenic response.
Project description:AbstractPancreatic cancer is one of the most aggressive malignancies. The poor prognosis of pancreatic cancer patients is mainly attributed to low diagnostic rate at the early stage, highly aggressive nature coupled with the inadequate efficacy of current chemotherapeutic regimens. Novel therapeutic strategies are urgently needed for pancreatic cancer. MicroRNAs (miRNAs) play an important regulatory role in key processes of cancer development. The aberrant expression of miRNAs is often involved in the initiation, progression, and metastasis of pancreatic cancer. The discovery of tumor suppressor miRNAs provides prospects for the development of a novel treatment strategy for pancreatic cancer. We reviewed recent progress on the understanding of the role of miRNAs in pancreatic cancer, highlighted the efficient application of miRNAs-based therapies for pancreatic cancer in animal models and clinical trials, and proposed future prospects. This review focuses on the promise of integrating miRNAs into the treatment of pancreatic cancer and provides guidance for the development of precision medicine for pancreatic cancer.
Project description:Colorectal cancer (CRC) is the most common malignant tumor and one of the most lethal malignant tumors in the world. Despite treatment with a combination of surgery, radiotherapy, and/or systemic treatment, including chemotherapy and targeted therapy, the prognosis of patients with advanced CRC remains poor. Therefore, there is an urgent need to explore novel therapeutic strategies and targets for the treatment of CRC. MicroRNAs (miRNAs/miRs) are a class of short noncoding RNAs (approximately 22 nucleotides) involved in posttranscriptional gene expression regulation. The dysregulation of its expression is recognized as a key regulator related to the development, progression and metastasis of CRC. In recent years, a number of miRNAs have been identified as regulators of drug resistance in CRC, and some have gained attention as potential targets to overcome the drug resistance of CRC. In this review, we introduce the miRNAs and the diverse mechanisms of miRNAs in CRC and summarize the potential targeted therapies of CRC based on the miRNAs.
Project description:Chronic itch is one of the most prominent clinical characteristics of diverse systematic diseases. It is a devastating sensation in pathological diseases. Despite its importance, there are no FDA-labelled drugs specifically geared toward chronic itch. The associated complex pathogenesis and diverse causes escalate chronic itch to being one of the top challenges in healthcare. Humanized antibodies against IL-13, IL-4, and IL-31 proved effective in treatment of itch-associated atopic dermatitis but remain to be validated in chronic itch. There are still no satisfactory anti-itch therapeutics available toward itch-related neuropeptides including GRP, BNP, SST, CGRP, and SP. The newly identified potential itch targets including OSM, NMB, glutamate, periostin, and Serpin E1 have opened new avenues for therapeutic development. Proof-of-principle studies have been successfully performed on antagonists against these proteins and their receptors in itch treatment in animal models. Their translational interventions in humans need to be evaluated. It is of great importance to summarize and compare the newly emerging knowledge on chronic itch and its pathways to promote the development of novel anti-itch therapeutics. The goal of this review is to analyze the different physiologies and pathophysiologies of itch mediators, whilst assessing their suitability as new targets and discussing future therapeutic development.
Project description:The discovery of microRNAs and their role in diseases was a breakthrough that inspired research into microRNAs as drug targets. Cardiovascular diseases are an area in which limitations of conventional pharmacotherapy are highly apparent and where microRNA-based drugs have appreciably progressed into preclinical and clinical testing. In this Review, we summarize the current state of microRNAs as therapeutic targets in the cardiovascular system. We report recent advances in the identification and characterization of microRNAs, their manipulation and clinical translation, and discuss challenges and perspectives toward clinical application.
Project description:MicroRNAs (miRNAs) are evolutionarily conserved, small, regulatory RNAs that negatively regulate gene expression. Extensive research in the last decade has implicated miRNAs as master regulators of cellular processes with essential role in cancer initiation, progression, and metastasis, making them promising therapeutic tools for cancer management. In this article, we will briefly review the structure, biogenesis, functions, and mechanism of action of these miRNAs, followed by a detailed analysis of the therapeutic potential of these miRNAs. We will focus on the strategies presently used for miRNA therapy; discuss their use and drawbacks; and the challenges and future directions for the development of miRNA-based therapy for human cancers.
Project description:The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, and transformation. The mTORC1, Myc, and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis. Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth. Myc is implicated in cancer development by enhancing RNA Pol II activity, leading to uncontrolled cancer cell growth. The deregulation of noncoding RNAs such as microRNAs, long noncoding RNAs, and circular RNAs is involved in developing blood, neurodegenerative diseases, and atherosclerosis. We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance. We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting, ribosome-stalling, and ribosome-collision. We summarize the role of ribosome biogenesis in the development of various diseases. Furthermore, we review the current clinical trials, prospective vaccines for COVID-19, and therapies targeting ribosome biogenesis in cancer, cardiovascular disease, aging, and neurodegenerative disease.
Project description:Stroke is one of the most devastating diseases worldwide. In recent years, a great number of studies have focused on the effects of microRNAs (miRNAs) on stroke and the results demonstrated that the expressions of miRNAs are associated with the prognosis of stroke. In the present study, we review relevant articles regarding miRNAs and stroke and will explain the complex link between both. The miRNAs participate extensively in the pathophysiology following the stroke, including apoptosis, neuroinflammation, oxidative stress, blood-brain barrier (BBB) disruption and brain edema. The information about the stroke-miRNA system may be helpful for therapeutic and diagnostic methods in stroke treatment.
Project description:Association studies have linked alterations of blood-derived microRNAs (miRNAs) with colorectal cancer (CRC). Here, we performed a microarray-based comparison of the profiles of 2549 miRNAs in 80 blood samples from healthy donors and patients with colorectal adenomas, colorectal diverticulitis and CRC at different stages. Confirmation by quantitative real-time PCR (RT-PCR) was complemented by validation of identified molecules in another 36 blood samples. No variations in miRNA levels were observed in samples from patients with colorectal adenomas and diverticulitis or from healthy donors. However, there were 179 CRC-associated miRNAs of differential abundance compared to healthy controls. Only three - miR-1225-5p, miR-1207-5p and miR-4459 - exhibited increased levels at all CRC stages. Most deregulated miRNAs (128/179, 71%) specifically predicted metastatic CRC. Pathway analysis found several cancer-related pathways to which the miRNAs contribute in various ways. In conclusion, miRNA levels in blood vary throughout CRC progression and affect cellular functions relevant to haematogenous CRC progression and dissemination. The identified biomarker and therapeutic candidates require further confirmation of their clinical relevance.
Project description:MicroRNAs are a class of small, non-coding RNAs that can negatively regulate protein-coding genes, and are associated with almost all known physiological and pathological processes, especially cancer. The number of studies documenting miRNA expression patterns in malignancy continues to expand rapidly, with continuously gained critical information regarding how aberrantly expressed miRNAs may contribute to carcinogenesis. miRNAs can influence cancer pathogenesis, playing a potential role as either oncogenes or tumour suppressors. Recently, several miRNAs have been reported to exert different regulatory functions in oesophageal cancer - the carcinoma typically arising from the epithelial lining of the oesophagus. These miRNAs also have potential clinical applications towards developing biomarkers or targets for possible use in diagnosis or therapy in oesophageal cancer. In this review, we have summarized the two (oncogenic or tumour suppressive) roles of miRNAs here, and their applications as potential biomarkers or therapeutic targets, which may illuminate future treatment for oesophageal cancer.