Dysfunction of microRNAs (miRNAs) is strongly proved to participate in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-944 was reported to play either oncogenic or tumor suppressive roles in human cancers. A recent study reported that the levels of miR-944 in recurrent CRC patients were evidently lower than that in non-recurrent cases, suggesting that miR-944 may function as a tumor suppressive miRNA in CRC. Yet, the clinical value and biological function of miR-944 remain rarely known in CRC. In the present study, we present that miR-944 level in CRC tissues is notably reduced compared to matched non-cancerous specimens. Its decreased level is evidently correlated with malignant clinical parameters and poor prognosis of CRC patients. Accordingly, the levels of miR-944 were obviously downregulated in CRC cells. Ectopic expression of miR-944 in CRC cells prominently inhibits the migration and invasion of tumor cells, while miR-944 knockdown increased these effects of CRC cells. Mechanically, miR-944 negatively regulated the metastasis-associated in colon cancer-1 (MACC1) abundance in CRC cells. Herein, MACC1 was found to be a downstream molecule of miR-944 in CRC. An inversely correlation between miR-944 and MACC1 was confirmed in CRC specimens. Furthermore, restoration of MACC1 expression could abrogate the anti-metastatic effects of miR-944 on CRC cells with enhanced cell migration and invasion. MACC1/Met/AKT signaling may be implicated with the function of miR-944 in CRC cells. Altogether, miR-944 potentially act as a prognostic predictor and a drug-target for CRC patients.
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http://dx.doi.org/10.3892/or.2017.5611 | DOI Listing |
Eur J Med Chem
January 2025
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science and Technology, Tianjin, 300457, China. Electronic address:
A series of isatin derivatives which could inhibit colorectal cancer (CRC) were synthesized. Among those compounds, 5B exhibited good inhibitory activity of CRC through the inhibition of tubulin expression, inducing apoptosis, and causing G2/M phase cell cycle arrest pathway, which suggested that 5B could be a potential tubulin inhibitor. Based on that, a novel peptide-drug conjugate (PDC), which employed the CRC cells related receptor CD44 ligand peptide A6 coupling to 5B to accomplish A6-5B.
View Article and Find Full Text PDFComb Chem High Throughput Screen
January 2025
Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
Objective: Colorectal Cancer (CRC) has attracted much attention due to its high mortality and morbidity. Cordycepin, also known as 3'-deoxyadenosine (3'-dA), exhibits many biological functions, including antibacterial, anti-inflammatory, antiviral, anti-tumor, and immunomodulatory effects. It has been proven to show anticancer activity in both laboratory research studies and living organisms.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
January 2025
Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, Barcelona 08028, Spain.
Blockade of the TGFβ signaling pathway has emerged from preclinical studies as a potential treatment to enhance the efficacy of immune checkpoint inhibition in advanced colorectal cancer (CRC) and several other types of cancer. However, clinical translation of first-generation inhibitors has shown little success. Here, we report the synthesis and characterization of HYL001, a potent inhibitor of TGFβ receptor 1 (ALK5), that is approximately 9 times more efficacious than the structurally related compound galunisertib, while maintaining a favorable safety profile.
View Article and Find Full Text PDFTheranostics
January 2025
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Colorectal cancer (CRC) is a leading cause of cancer-related mortality. Epigenetic modifications play a significant role in the progression of CRC. KAT7, a histone acetyltransferase, has an unclear role in CRC.
View Article and Find Full Text PDFJ Gastrointest Oncol
December 2024
Medical Physics Unit, Department of Oncology, Faculty of Medicine, McGill University, Montreal, QC, Canada.
Background: Orthotopic models offer a more accurate representation of colorectal cancer (CRC) compared to subcutaneous models. Despite promising results from the reported intra-rectal models, establishing a standardized method for CRC research remains challenging due to model variability, hindering comprehensive studies on CRC pathogenesis and treatment modalities, such as brachytherapy. This study aimed to establish a standardized workflow for an orthotopic intra-rectal animal model to induce the growth of colorectal adenocarcinoma in male and female mice.
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