MicroRNAs (miRNAs/miRs), non-coding single-stranded RNAs of length 18-24 nucleotides, can modulate gene expression through post-transcriptional control. As such, they can influence tumor proliferation, apoptosis, invasion, metastasis as well as chemotherapy resistance by regulating certain downstream genes. In this context, miR-200b-3p, one particular member of the miR-200 family, possesses the ability to suppress tumor progression. However, many studies have suggested that, in certain cases, this miRNA may also promote the development of some tumors due to differences in the microenvironments and molecular backgrounds of different cancers. This review summarizes previous studies on the involvement of miR-200b-3p in tumors, including the underlying mechanism. Contents 1. Introduction 2. Mechanism of action of miR-200b-3p in cancer 3. miR-200b-3p function is dependent on cancer type 4. Mechanism of miR-200b-3p regulation 5. Conclusion
Novel nitro oxide (NO)-donating N-hydroxycinnamamide derivatives 12a-j were designed and synthesized by coupling the carboxyl group of N-hydroxycinnamamides with phenylsulfonylfuroxan through various diols or alkylol amines, and their in vitro biological activities were evaluated. It was discovered that most of target compounds showed good histone deacetylases (HDACs) inhibition and anti-tumor activities, particularly for 12j, which had great HDACs inhibitory activities (IC 50 s 0.15-0.26 µM) and antiproliferative effects (IC 50 s 3.21-7.12 µM) comparable to suberoylanilide hydroxamic acid (SAHA) (IC 50 s 0.16-1.41 µM for HDACs, IC 50 s 3.15-7.45 µM for cancer cell inhibition). Furthermore, compound 12j with strong antitumor activities produced high levels of NO (up to 8.0 µM of nitrites/nitrates) in colon cancer cells, and its antiproliferative activity was nearly half-diminished by hemoglobin (10 µM), an NO scavenger. These results suggest that the strong antiproliferative activity of 12j could be attributed to the additive effects of high levels of NO production and inhibition of HDAC in the cancer cells.Key words nitro oxide; histone deacetylase inhibitor; furoxan; N-hydroxycinnamamide; anti-tumor agent Pharmacological targeting of proteins that regulate epigenetics has emerged as a promising therapeutic area of study.1,2) Epigenetic or chromatin modification is recognized by nonhistone proteins and is a code of gene expression. Among the various histone modifiers, Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are two reversible enzymes regulating histone acetylation status and executing the acetylation and deacetylation of the lysine residues at the amino terminal of histones.3) However, abnormal HDAC overexpression has been found to be involved in the development of several kinds of human cancers, including myeloid neoplasia and solid tumors. 4) Recent studies have shown that acetylation of non-histone proteins is also relevant for tumorigenesis, cancer cell proliferation, and immune functions.5) Consequently, histone deacetylases are considered to be important targets in the development of anticancer agents, and in recent years considerable attention has been paid to HDAC inhibitors (HDACI) as anticancer agents. [6][7][8] There has been a high level of interest in developing smallmolecule HDACI, and numerous structurally diverse HDACI have been developed as potential anticancer agents, which are grouped chemically into four classes: hydroxamic acids, benzamides, cyclic tetrapeptides, and short-chain fatty acids.9) The common pharmacophore of these HDACI consists of three domains: a zinc-binding group (ZBG), such as hydroxamic acid; a cap group, generally a hydrophobic and aromatic group; a saturated or unsaturated linker domain, composed of linear or cyclic structures that connect the ZBG and the cap group. Up to now, two of these HDACI, suberoylanilide hydroxamic acid (SAHA, Fig. 1) and cyclic peptide Romidepsin (FK228), have been approved by the U.S. Food and Drug Administration (FDA) f...
Colorectal cancer is one of the common malignant tumors in the digestive system, with high incidence and mortality rate. Therefore, there is an urgent need to identify and develop new molecular targets for colorectal cancer treatment. Previous studies have pointed out the important role of HMGB3 in tumors, and how it works in colorectal cancer needs to be studied in depth. In this study, we found that HMGB3 was highly expressed in COAD in the cBioPortal and GEPIA2 databases. Kaplan-Meier analysis showed that compared with patients with lower HMGB3 levels, patients with higher HMGB3 levels had poorer OS (p = 0.001). We also found a correlation between HMGB3 expression and immune infiltration of CRC. To investigate the mechanism of HMGB3 knockdown-mediated colorectal cancer inhibition, we detected a downregulation of N-cadherin, Vimentin and β-catenin proteins after knockdown of HMGB3. Taken together, HMGB3 can be an effective target for CRC treatment in the future, and we have reason to believe that HMGB3 will be of greater value in more tumors in the near future.
Hypoxia-mediated tumor progression is a major problem in colorectal cancer (CRC). MicroRNA (miR)-200b-3p can attenuate tumorigenesis in CRC, while exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) can promote cancer progression. Nevertheless, the function of exosomal miR-200b-3p derived from CAFs in CRC remains unclear. In this study, CAFs and normal fibroblasts (NFs) were isolated from CRC and adjacent normal tissues. Next, exosomes were isolated from the supernatants of CAFs cultured under normoxia and hypoxia. Cell viability was tested using the cell counting kit-8 assay, and flow cytometry was used to assess cell apoptosis. Cell invasion and migration were evaluated using the transwell assay. Dual-luciferase was used to investigate the relationship between miR-200b-3p and high-mobility group box 3 (HMBG3). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the miR-200b-3p and HMBG3 level. Our results found that the miR-200b-3p level was sharply reduced in CRC tissues compared to adjacent normal tissues. Additionally, the miR-200b-3p level was reduced in exosomes derived from hypoxic CAFs compared to exosomes derived from CAFs under normoxia. Exosomes derived from hypoxic CAFs weakened the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. However, hypoxic CAFs-derived exosomes with upregulated miR-200b-3p increased the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. In addition, HMBG3 was identified as the downstream target of miR-200b-3p in CRC cells, and its overexpression partially reversed the anti-tumor effect of the miR-200b-3p agomir on CRC via the mediation of the β-catenin/c-Myc axis. Furthermore, compared to exosomes derived from normoxia CAFs, exosomes derived from hypoxic CAFs weakened the therapeutic effects of 5-FU on CRC in vivo via the upregulation of HMGB3 levels. Collectively, the loss of exosomal miR-200b-3p in hypoxia CAFs reduced the sensitivity to 5-FU in CRC by targeting HMGB3. Thus, our research outlines a novel method for the treatment of CRC.
It is well-established that there are trillions of gut microbiota (GM) in the human gut. GM and its metabolites can reportedly cause cancer by causing abnormal immune responses. With the development of sequencing technology and the application of germ-free models in recent years, significant inroads have been achieved in research on GM and microbiota-related metabolites. Accordingly, the role and mechanism of GM in colorectal cancer (CRC) development have been gradually revealed. Traditional Chinese medicine (TCM) represents an important source of natural medicines and herbal products, with huge potential as anti-CRC agents. The potential application of TCM to target gut microbes for the treatment of colorectal cancer represents an exciting area of investigation.
Background: To construct clinical and machine learning nomogram to predict the lymph node metastasis (LNM) status of rectal carcinoma (RC) based on radiomics and clinical characteristics. Methods: 788 RC patients were enrolled from January 2015 to January 2021, including 303 RCs with LNM and 485 RCs without LNM. The radiomics features were calculated and selected with the methods of variance, correlation analysis, and gradient boosting decision tree. After feature selection, the machine learning algorithm of Bayes, k-nearest neighbor (KNN), logistic regression (LR), support vector machine (SVM), and decision tree (DT) were used to construct prediction models. The clinical characteristics combined with intratumoral and peritumoral radiomics was taken to develop a radiomics and machine learning nomogram. The relative standard deviation (RSD) was used to predict the stability of machine learning algorithm. The area under curves (AUCs) with 95% confidence interval (CI) were calculated to evaluate the predictive efficacy of all models.Results: To intratumoral radiomics analysis, the RSD of Bayes was minimal compared with other four machine learning algorithms. The AUCs of arterial-phase based intratumoral Bayes model (0.626 and 0.627) were higher than these of unenhanced-phase and venous-phase ones in both the training and validation group.The AUCs of intratumoral and peritumoral Bayes model were 0.656 in the training group and were 0.638 in the validation group, and the relevant Bayes-score was quantified. The clinical-Bayes nomogram containing significant clinical variables of diameter, PNI, EMVI, CEA, and CA19-9, and Bayes-score was constructed. The AUC (95%CI), specificity, and sensitivity of this nomogram was 0.828 (95%CI, 0.800-0.854), 74.85%, and 77.23%.Conclusion: Intratumoral and peritumoral radiomics can help predict the LNM status of RCs. The machine learning algorithm of Bayes in arterial-phase performed better in consideration of terms of RSD and AUC. The clinical-Bayes nomogram better predicted the LNM status of RCs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.