MicroRNAs (miRNAs) are short, noncoding, single-stranded RNA molecules that regulate gene expression at the post-transcriptional level by binding to mRNAs. miRNAs affect the course of processes of fundamental importance for the proper functioning of the organism. These processes include cell division, proliferation, differentiation, cell apoptosis and the formation of blood vessels. Altered expression of individual miRNAs has been shown in numerous cancers, which may indicate the oncogenic or suppressor potential of the molecules in question. This paper discusses the current knowledge about the possibility of using miRNA as a diagnostic marker and a potential target in modern anticancer therapies.

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miRNAs in Cancer (Review of Literature)

Colorectal cancer (CRC) is one of the most common cancers worldwide. The diagnosis, prognosis and therapeutic monitoring of CRC depends largely on tissue biopsy. However, due to tumor heterogeneity and limitations such as invasiveness, high cost and limited applicability in longitudinal monitoring, liquid biopsy has gathered immense attention in CRC. Liquid biopsy has several advantages over tissue biopsy including ease of sampling, effective monitoring, and longitudinal assessment of treatment dynamics. Furthermore, the importance of liquid biopsy is signified by approval of several liquid biopsy assays by regulatory bodies indicating the powerful approach of liquid biopsy for comprehensive CRC screening, diagnostic and prognostics. Several liquid biopsy biomarkers such as novel components of the microbiome, non-coding RNAs, extracellular vesicles and circulating tumor DNA are extensively being researched for their role in CRC management. Majority of these components have shown promising results on their clinical application in CRC including early detection, observe tumor heterogeneity for treatment and response, prediction of metastases and relapse and detection of minimal residual disease. Therefore, in this review, we aim to provide updated information on various novel liquid biopsy markers such as a) oral microbiota related bacterial network b) gut microbiome-associated serum metabolites c) PIWI-interacting RNAs (piRNAs), microRNA(miRNAs), Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and d) circulating tumor DNAs (ctDNA) and circulating tumor cells (CTC) for their role in disease diagnosis, prognosis, treatment monitoring and their applicability for personalized management of CRC. 

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Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer

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Aims Naturally secreted extracellular vesicles (EVs) play important roles in stem-mediated cardioprotection. This study aimed to investigate the cardioprotective function and underlying mechanisms of EVs derived from HIF-1α engineered mesenchymal stem cells (MSCs) in a rat model of AMI. Methods and rResults EVs isolated from HIF-1α engineered MSCs (HIF-1α-EVs) and control MSCs (NC-EVs) were prepared. In in vitro experiments, the EVs were incubated with cardiomyocytes and endothelial cells exposed to hypoxia and serum deprivation (H/SD); in in vivo experiments, the EVs were injected in the acutely infarcted hearts of Sprague-Dawley rats. Compared with NC-EVs, HIF-1α-EVs significantly inhibited the apoptosis of cardiomyocytes and enhanced angiogenesis of endothelial cells; meanwhile, HIF-1α-EVs also significantly shrunk fibrotic area and strengthened cardiac function in infarcted rats. After treatment with EVs/RGD-biotin hydrogels, we observed longer retention, higher stability in HIF-1α-EVs, and stronger cardiac function in the rats. Quantitative real-time PCR (qRT-PCR) displayed that miRNA-221–-3p was highly expressed in HIF-1α-EVs. After miR-221–-3p was inhibited in HIF-1α-EVs, the biological effects of HIF-1α EVs on apoptosis and angiogenesis were attenuated. Conclusion EVs released by MSCs with HIF-1α overexpression can promote the angiogenesis of endothelial cells and the apoptosis of cardiomyocytes via upregulating the expression of miR-221–-3p. RGD hydrogels can enhance the therapeutic efficacy of HIF-1α engineered MSCs-derived EVs.

HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated aArginine-gGlycine-aAspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction

The gastrointestinal (GI) tract in mammals is comprised of dozens of cell types with varied functions, structures, and histological locations that respond in a myriad of ways to epigenetic and genetic factors, environmental cues, diet, and microbiota. The homeostatic functioning of these cells contained within this complex organ system has been shown to be highly regulated by the effect of microRNAs (miRNA). Multiple efforts have uncovered that these miRNAs are often tightly influential in either the suppression or overexpression of inflammatory, apoptotic, and differentiation-related genes and proteins in a variety of cell types in colorectal cancer (CRC). The early detection of CRC and other GI cancers can be difficult, attributable to the invasive nature of prophylactic colonoscopies. Additionally, the levels of miRNAs associated with CRC in biofluids can be contradictory and, therefore, must be considered in the context of other inhibiting competitive endogenous RNAs (ceRNA) such as lncRNAs and circRNAs. There is now a high demand for disease treatments and noninvasive screenings such as testing for bloodborne or fecal miRNAs and their inhibitors/targets. The breadth of this review encompasses current literature on well-established CRC-related miRNAs and the possibilities for their use as biomarkers in the diagnoses of this potentially fatal GI cancer.

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MicroRNAs and ‘Sponging’ Competitive Endogenous RNAs Dysregulated in Colorectal Cancer: Potential as Noninvasive Biomarkers and Therapeutic Targets

Colorectal cancer cell-derived extracellular vesicles transfer miR-221-3p to promote endothelial cell angiogenesis via targeting suppressor of cytokine signaling 3.

Background: TGF-β signaling plays a key role in the performance of leukemic stem cells (LSCs). According to the evidence, any disturbance in the TGF beta pathway function not only poses negative effects on the development of BCR-ABL-induced chronic myeloid leukemia (CML) but also depletes CML stem cells. Hence, it can be argued that the aberrant acquisition of self-renewal characteristic because of the aberrant activation of TGF-β signaling results in the CML progression, which indicates the importance of inhibiting other targets besides BCR-ABL, such as TGF-β signaling, that can regulate self-renewal of the leukemic, which in turn translates into inhibited growth of BCR-ABL-positive CD34+ LSCs. Methods: The CD4+ cells were isolated from three CML patients with no history of treatments. The cells were cultured in a Stemspan H3000 medium. After being characterized by flow cytometry, the CML CD4+ cells were transfected with miR-144. The expression levels of miR-144, Smad4, and TGFβR2 genes were evaluated by RT-PCR. The impact of miR-144 overexpression on CML CD4+ cells was determined by the evaluation of cellular proliferation. Results: Overexpression of miR-144 resulted in the down-regulation of Smad4 and TGF-βR2 and decreased cell proliferation in CML CD34+ cells. Conclusions: This study suggests the down-regulation of miR-144 as a potential contributor to CML pathogenesis by activating the oncogenic TGF-β pathway. Hence, the proliferation capability of CD34+ CML cells, as a potential source of relapse in CML patients, can be inhibited by restoring miR-144 expression.

Sara Zareian

Papers

Colorectal cancer cell-derived extracellular vesicles transfer miR-221-3p to promote endothelial cell angiogenesis via targeting suppressor of cytokine signaling 3.

Up-regulation of miR-144 Inhibits CML CD34+ Cell Proliferation Through Modulating TGF-β Signaling