GSE134442 miR-4711-5p regulates the cancer stemness and cell cycle progression through direct binding to KLF5, MDM2 and TFDP1 in colon cancer cells

In this study, we searched for candidate microRNAs (miRNAs) by in silico analyses, which inhibit a stem cell-related gene Kr üppel-like factor 5 (KLF5). After in vitro screening we focused on miR-4711-5p which proved to inhibit cancer stemness and G1-S cell cycle progression. We found by luciferase binding assays that miR-4711-5p directly bound to KLF5, TFDP1 (a heterodimeric partner with E2F family), and MDM2 (one respo nsible gene for degradation of wild type p53). This miRNA suppressed cell proliferation, migration, and invasion ability in DLD-1 and HCT116 cells as well as the cancer stemness including low reactive oxygen species (ROS) activity, and sphere formation ability. The expressions of stem cell markers, LGR5, CD44v9, and BMI1 also decreased. MiR-4711-5p inhibited the in vivo growth of pre-established DLD-1 xenografts without apparent adverse effect. RNA sequence Analyses indicated that the transition from G1 phase to S phase in cell cycle was disturbed by miR-4711-5p. We indeed found that miR-471 1-5p provoked G1 arrest with increase in CDK inhibitor p27KIP1 and/or p21WAF1/CIP1 and decrease in CDK2, 4, 6 and Cyclin D1 protein expression. These changes could be attributed to direct binding of miR-4711-5p to TFDP1. It is also suggested that down-regulation of MDM2 could permit to accumulate th e wild type p53 protein in HCT116, leading to drastic induction of the p21WAF1/CIP1 protein and apoptosis. Our data suggest that miR-4711-5p could be a hopeful next gene...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Melatonin is a physiological hormone produced by the pineal gland. In recent decades, enormous investigations showed that melatonin can prompt apoptosis in cancer cells and inhibit tumor metastasis and angiogenesis in variety of malignancies such as ovarian, melanoma, colon, and breast cancer; therefore, its possible therapeutic usage in cancer treatment was confirmed. CSCs, which has received much attention from researchers in past decades, are major challenges in the treatment of cancer. Because CSCs are resistant to chemotherapeutic drugs and cause recurrence of cancer and also have the ability to be r...
Source: Pathology, Research and Practice - Category: Pathology Authors: Tags: Pathol Res Pract Source Type: research
This study demonstrates that haploinsufficiency of c-Cbl results in Wnt hyperactivation in intestinal crypts and accelerates CRC progression to adenocarcinoma in the milieu of APCΔ14/+, a phenomenon not found with wild-type APC. While emphasizing the role of APC as a gatekeeper in CRC, this study also demonstrates that combined partial loss of c-Cbl and inactivation of APC significantly contribute to CRC tumorigenesis. PMID: 32113662 [PubMed - as supplied by publisher]
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research
Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors associated with high cardiovascular morbidity and variable risk of malignancy. The current therapy of choice is surgical resection. Nevertheless, PCCs/PGLs are associated with a lifelong risk of tumor persistence or recurrence. A high rate of germline or somatic mutations in numerous genes has been found in these tumors. For some, the tumorigenic processes are initiated during embryogenesis. Such tumors carry gene mutations leading to pseudohypoxic phenotypes and show more immature characteristics than other chromaffin cell tumors; they are also ...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
AbstractDigestive system cancers are the most frequent cancers worldwide and often associated with poor prognosis because of their invasive and metastatic characteristics. Recent studies have found that the plasticity of cancer cells can impart cancer stem-like properties via the epithelial –mesenchymal transition (EMT). Cancer stem-like properties such as tumor initiation are integral to the formation of metastasis, which is the main cause of poor prognosis. Numerous markers of cancer stem cells (CSCs) have been identified in many types of cancer. Therefore, CSCs, via their stem cel l-like functions, may play an imp...
Source: Surgery Today - Category: Surgery Source Type: research
In this study we investigated the effect of curcumin on cancer cell viability, proliferation and suppression of CSCs markers (CD44, CD133, ALDH1) in vitro. Additionally, as limitations for curcumin application arise from its poor bioavailability, the stability of curcumin in different media conditions was investigated.The effect of curcumin on three cancer cell lines (A549, HCT116, 183E95) was investigated with MTT-assay, Flowcytometry, Immunofluorescence and western blotting. Stability of curcumin (diferuloylmethane) and curcuminoids (bisdemetoxycurcumin; desmetoxycurcumin) was determined by HPLC technique in A549 cells i...
Source: Journal of Herbal Medicine - Category: Complementary Medicine Source Type: research
Abstract Various Long non-coding RNAs (lncRNAs) and MicroRNAs (miRNAs) have been demonstrated to be involved in colorectal cancer stem cells (CSCs). WBSCR22 is a key gene we previously found that functions in colorectal cancer (CRC). This paper aims to investigate the effects of WBSCR22 and its corresponding miRNA and lncRNA in CRC. The expression of WBSCR22 was detected by Western blot and qRT-PCR analysis. Tumor sphere formation assays, CCK-8 analysis, and Transwell assays were applied to examine the colorectal cancer stem cell properties. Luciferase assay and biotin RNA pulldown assay were used to detect the in...
Source: Biochemical Genetics - Category: Genetics & Stem Cells Authors: Tags: Biochem Genet Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, our results demonstrate that DCLK1 is linked with functional regulation of the tumor microenvironment and may have potential as a prognostic biomarker and adjuvant target to promote immunotherapy sensitivity in colon and gastric cancer patients.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
This study aimed to analyze the role and content of sEVs released during the differentiation of colorectal cancer stem cells. Here we show that sEVs secretion during colon cancer stem cells differentiation is partially controlled by CD147, a well-known player involved in colon cancer tumorigenesis. CD147 + sEVs activate a signaling cascade in recipient cells inducing molecular invasive features in colon cancer cells. CD147 knockdown as well as anti-CD147 antibodies impaired sEVs release and downstream effects on recipient cells and blocking multivesicular body maturation prevented sEVs release during the differentiation. O...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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