The Simultaneous Effects of miR-145-5p and hsa-let-7a-3p on Colorectal Tumorigenesis: In Vitro Evidence.

Purpose: MicroRNAs (miRNAs) are a group of small regulatory non-coding RNAs, which are dysregulated through tumor progression. let-7 and MIR-145 are both tumor suppressor microRNAs that are downregulated in a wide array of cancers including colorectal cancer (CRC). Methods: This study was aimed to investigate the effect of simultaneous replacement of these two tumor suppressor miRNAs on proliferation, apoptosis, and migration of CRC cells. HCT-116 with lower expression levels of hsa-let-7a-3p and MIR-145-5p was selected for functional investigations. The cells were cultured and transfected with hsa-let-7a and MIR-145, separately and in combination. Cell viability and apoptosis rates were assessed by MTT assay and flow cytometry, respectively. Cell cycle status was further evaluated using flow cytometry and qRT-PCR was employed to evaluate gene expression. Results: The obtained results showed that exogenous overexpression of MIR-145 and hsa-let-7a in HCT-116 cells could cooperatively decrease CRC cell proliferation and induce sub-G1 cell cycle arrest. Moreover, hsa-let-7a and MIR-145 co-transfection significantly increased apoptosis induction compared to separate transfected cells and control through modulating the expression levels of apoptosis-related genes including Bax, Bcl-2, P53, Caspase-3, Caspase-8, and Caspase-9. Furthermore, qRT-PCR results illustrated that hsa-let-7a and MIR-145 combination more effectively downregulated MMP-9 and MMP-2 expression, as the important modulators of metastasis, compared to the controls. Conclusion: Taken together, considering that exogenous overexpression of MIR-145 and hsa-let-7a showed cooperative anti-cancer effects on CRC cells, their combination may be considered as a novel therapeutic strategy for the treatment of CRC.

Simultaneous suppression of miR-21 and restoration of miR-145 in gastric cancer cells; a promising strategy for inhibition of cell proliferation and migration.

Introduction: Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. microRNAs are a group of regulatory non-coding RNAs that are involved in GC progression. miR-145 as a tumor suppressor and miR-21 as an oncomiR were shown to be dysregulated in many cancers including GC. This research aimed to enhance the expression of miR-145 while reducing the expression of miR-21 and examine their impact on the proliferation, apoptosis, and migration of GC cells. Methods: KATO III cells with high expression levels of miR-21-5p and low expression of miR-145-5p were selected. These cells were then transfected with either miR-145-5p mimics or anti-miR-21-5p, alone or in combination. Afterward, the cell survival rate was determined using the MTT assay, while apoptosis induction was investigated through V-FITC/PI and DAPI staining. Additionally, cell migration was examined using the wound healing assay, and cell cycle progression was analyzed through flow cytometry. Furthermore, gene expression levels were quantified utilizing the qRT-PCR technique. Results: The study's findings indicated that the co-replacement of miR-145-5p and anti-miR-21-5p led to a decrease in cell viability and the induction of apoptosis in GC cells. This was achieved via modulating the expression of Bax and Bcl-2, major cell survival regulators. Additionally, the combination therapy significantly increased sub-G1 cell cycle arrest and reduced cell migration by downregulating MMP-9 expression as an epithelial-mesenchymal transition marker. This study provides evidence for the therapeutic possibility of the combination of miR-145-5p and anti-miR-21-5p and also suggests that they could inhibit cell proliferation by modulating the PTEN/AKT1 signaling pathway. Conclusion: Our research revealed that utilizing miR-145-5p and anti-miR-21-5p together could be a promising therapeutic approach for treating GC.

MiR-145 inhibits cell migration and increases paclitaxel chemosensitivity in prostate cancer cells.

Objectives: Prostate cancer (PC) is one of the most commonly diagnosed malignancies among men worldwide. Paclitaxel is a chemotherapeutic agent widely used to treat different types of cancer. Recent studies revealed miRNAs control various genes that influence the regulation of many biological and pathological processes such as the formation and development of cancer, chemotherapy resistance, etc. Materials and Methods: Between three PC cell lines (PC3, DU-145, LNCAP), PC3 showed the lowest miR-145 expression and was chosen for experiments. PC3 cells were treated with paclitaxel and miR-145 separately or in combination. To measure the cell viability, migratory capacity, autophagy, cell cycle progression, and apoptosis induction, the MTT assay, wound-healing assay, and Annexin V/PI apoptosis assay were used, respectively. Moreover, quantitative real-time PCR (qRT-PCR) was employed to measure the expression level of genes involved in apoptosis, migration, and stemness properties. Results: Obtained results illustrated that miR-145 transfection could enhance the sensitivity of PC3 cells to paclitaxel and increase paclitaxel-induced apoptosis by modulating the expression of related genes, including Caspase-3, Caspase-9, Bax, and Bcl-2. Also, results showed combination therapy increased cell cycle arrest at the sub-G1 phase. miR-145 and paclitaxel cooperatively reduced migration ability and related-metastatic and stemness gene expression, including MMP-2, MMP-9, CD44, and SOX-2. In addition, combination therapy can suppress MDR1 expression. Conclusion: These results confirmed that miR-145 combined with paclitaxel cooperatively could inhibit cell proliferation and migration and increase the chemosensitivity of PC3 cells compared to mono treatment. So, miR-145 combination therapy may be used as a promising approach for PC treatment.

The emerging role of MicroRNA-182 in tumorigenesis; a promising therapeutic target.

A wide range of studies have indicated that microRNAs (miRNAs), a type of small single-stranded regulatory RNAs, are dysregulated in a different variety of human cancers. Therefore, they are expected to play important roles in tumorigenesis by functioning as oncogenic (oncomiRs) or tumor-suppressive miRNAs. Subsequently, their potential as diagnostic and therapeutic targets for malignancies has attracted attention in recent years. In particular, studies have revealed the aberrant expression of miR-182 through tumorigenesis and its important roles in various aspects of malignancies, including proliferation, metastasis, and chemoresistance. Accumulating reports have illustrated that miR-182, as a dual-role regulator, directly or indirectly regulates the expression of a wide range of genes and modulates the activity of various signaling pathways involved in tumor progression, such as JAK / STAT3, Wnt / ß-catenin, TGF-ß, and P13K / AKT. Therefore, considering the high therapeutic and diagnostic potential of miR-182, this review aims to point out the effects of miR-182 dysregulation on the signaling pathways involved in tumorigenesis.

MicroRNA-425: A Pivotal Regulator Participating in Tumorigenesis of Human Cancers.

MicroRNAs (miRNAs) are small single-stranded regulatory RNAs that are shown to be dysregulated in a wide array of human cancers. MiRNAs play critical roles in cancer progression and function as either oncogenes or tumor suppressors through modulating various target genes. Therefore, they possess great potential as diagnostic and therapeutic targets for cancer detection and treatment. In particular, recent studies have illustrated that miR-425 is also dysregulated in various human malignancies and plays a fundamental role in cancer initiation and progression. miR-425 has been reported to function as a dual-role miRNA participating in the regulation of cellular processes, including metastasis, invasion, and cell proliferation by modulating multiple signaling pathways, such as TGF-ß, Wnt, and P13K/AKT pathways. Therefore, regarding recent researches showing the high therapeutic potential of miR-425, in this review, we have noted the impact of its dysregulation on signaling pathways and various aspects of tumorigenesis in a variety of human cancers.

Synergistic anticancer effects of curcumin and crocin on human colorectal cancer cells.

BACKGROUND: Curcumin, a polyphenol compound derived from the Curcuma longa L, and crocin, a hydrophilic carotenoid from Crocus Sativus Linnaeus, are traditionally used in food preparations in many countries and could act as chemopreventive compounds against several diseases, including cancer. In this study, the synergistic effect of curcumin and crocin was investigated for the first time on inducing apoptosis and suppressing colorectal cancer cells (SW-480 cell line). METHODS AND RESULTS: MTT, Annexin V-FITC/PI, and DAPI staining tests were employed to evaluate cell viability and apoptosis induction, respectively. The combined effect of curcumin and crocin on the expression of genes involved in apoptosis and proliferation was quantified using real-time PCR. The combination therapy effect on cell cycle progression was also evaluated by flow cytometry. Based on the obtained results, curcumin and crocin treatment could cooperatively reduce cell viability and induce apoptosis in SW-480 cells by modulating the expression of Bax, Bcl-2, Caspase-3, Caspase-8, Caspase-9, Jak2, Stat3, and Akt1 genes. Besides, curcumin and crocin were able to synergistically increase the cell cycle arrest at the sub G1 phase, induce autophagy and decrease the clonogenic ability of SW-480 cells. CONCLUSIONS: These results suggested that curcumin and crocin combination could be considered a more effective therapeutic strategy for inhibiting colorectal cancer.

Lateral flow assays (LFA) for detection of pathogenic bacteria: A small point-of-care platform for diagnosis of human infectious diseases.

Up-to-date diagnostics is globally improved by point-of-care testing (POCT) analysis and bedside research works. Development in POCT analysis has been provided mostly by forward-looking engineering technology for biosensing and sensing assessments. Lately, lateral flow assays (LFAs) have attracted a lot of interest as a result of their noteworthy benefits including cost-effectiveness, better portability, being operator friendly and rapid detection. This technique has been employed broadly for monitoring diverse biomarkers linked to ultrasensitive detection of pathogenic bacteria, ecological monitoring, consumer protection, and infectious diseases. LFA analyses established on qualitative and optical outcomes have boosted the objectivity and data efficiency of the assessments. Therefore, developing novel methods with the capability of providing reliable and quantitative information regarding a target analyte in a model and preserving the qualities of LFAs is of great necessity. In this review, the main principles of LFAs, challenges, and prospects for more development in this field in sensing pathogenic bacteria have been summarized. Subsequently, visually-read LFAs improvement to further progressive platforms have been explored by considering the prospects of this very flexible method for ultrasensitive detection of pathogenic bacteria. In addition, novel labeling methodologies, electrochemical and optical transducers are described. Also, recent developments in these detection methods elements in combination with other considered approaches have been highlighted.

Lateral flow assays (LFA) as an alternative medical diagnosis method for detection of virus species: The intertwine of nanotechnology with sensing strategies.

Viruses are responsible for multiple infections in humans that impose huge health burdens on individuals and populations worldwide. Therefore, numerous diagnostic methods and strategies have been developed for prevention, management, and decreasing the burden of viral diseases, each having its advantages and limitations. Viral infections are commonly detected using serological and nucleic acid-based methods. However, these conventional and clinical approaches have some limitations that can be resolved by implementing other detector devices. Therefore, the search for sensitive, selective, portable, and costless approaches as efficient alternative clinical methods for point of care testing (POCT) analysis has gained much attention in recent years. POCT is one of the ultimate goals in virus detection, and thus, the tests need to be rapid, specific, sensitive, accessible, and user-friendly. In this review, after a brief overview of viruses and their characteristics, the conventional viral detection methods, the clinical approaches, and their advantages and shortcomings are firstly explained. Then, LFA systems working principles, benefits, classification are discussed. Furthermore, the studies regarding designing and employing LFAs in diagnosing different types of viruses, especially SARS-CoV-2 as a main concern worldwide and innovations in the LFAs' approaches and designs, are comprehensively discussed here. Furthermore, several strategies addressed in some studies for overcoming LFA limitations like low sensitivity are reviewed. Numerous techniques are adopted to increase sensitivity and perform quantitative detection. Employing several visualization methods, using different labeling reporters, integrating LFAs with other detection methods to benefit from both LFA and the integrated detection device advantages, and designing unique membranes to increase reagent reactivity, are some of the approaches that are highlighted.